Some familiarity with electronic circuits and using breadboards would be helpful, though it is not required for this project. Build a model of an artificial pancreas to investigate the challenges of getting such a device to work. First, let us step back for a moment and have a quick crash course (or a refresher if you are already familiar) on diabetes. This video shows how blood glucose levels change over time for people with and without diabetes (Khan Academy, 2011). However, in people with type 1 diabetes (which is caused by an autoimmune response, and was formerly known as juvenile diabetes), the pancreas no longer makes insulin. While the solution for many diabetics is to take insulin, it is not that simple; many things have an effect on insulin levels in a person's body, including exercise, stress, what and how much they eat, just to name a few. As previously discussed, to take away the difficulties of managing type 1 diabetes, scientists and engineers have set out to create improved insulin pumps and an artificial pancreas. Now that you have a better understanding of type 1 diabetes and what an artificial pancreas is, you may be wondering how you can work on something like that for a science fair project. When enough electrical current travels through the conductivity sensor, it causes a transistor in the circuit to activate a pump. Lastly, the conductivity sensor is combined with other electrical components called potentiometers, which are a type of adjustable resistor.
Do you think it will be difficult to get the artificial pancreas to stop when it is supposed to, when the right amount of baking soda solution has been added to the vinegar solution?
What do the different parts of the artificial pancreas model in this project represent in a real artificial pancreas system? If you are using a graduated cylinder, you will also want to have a funnel that fits with the top of the graduated cylinder. Scissors; in addition to cutting Styrofoam and a plastic straw, you will also need to cut some copper wire. We also do our best to make sure that any listed supplier provides prompt, courteous service. Proceeds from the affiliate programs help support Science Buddies, a 501(c)(3) public charity.
In this part of the procedure, you will make a conductivity sensor and connect it to your breadboard circuit. If possible, one end of the segment should have the ridged, bendable part of the straw on it; this will help keep the wire on the sensor. Wrap the end of each copper wire tightly around the straw, looping it about four times with each wire, as shown in Figure 5.
The wire should be wound tightly around the straw so that the wire does not easily slide around on the straw. However, even if the wires do move some, this should be fixed when you add the Styrofoam piece next. Carefully poke the copper wire tails from the straw through the Styrofoam piece, keeping the wires the same distance apart that they are on the straw piece, as shown in Figure 6. On the top side of the Styrofoam (opposite the side where the straw is), make a sharp bend in each wire, right above the Styrofoam, as shown in Figure 7.
The sensor will be going into a bowl of liquid, and the amount of copper wire submerged in the liquid can change how much conductivity the sensor detects.
Lastly, attach the unconnected alligator clip leads from your circuit to the copper wires on the sensor, as shown in Figure 8. For labeling, you can use masking tape and a permanent marker or small sticky notes and a pen or pencil. On a scale, place a measuring cup or other small container to weigh baking soda on the scale. Use the graduated cylinder, or a metric measuring cup, to measure out 200 milliliters (mL) of distilled water. Measure out 100 mL of distilled white vinegar and very slowly add it to the "Neutralized" bowl.
Caution: Mixing an acidic solution with a basic solution can cause a powerful chemical reaction. Once the reaction has slowed, slowly mix the solution to make sure the vinegar and baking soda have completely reacted. Measure out 200 mL of distilled white vinegar and carefully pour it into the "Vinegar" bowl.
To find out what the pH of the baking soda solution, the vinegar and the neutralized solution is, add about 1 teaspoon of bromothymol blue indicator solution to each bowl. Carefully place your conductivity sensor in the "Neutralized" bowl, letting the straw part be submerged and the Styrofoam piece float on the surface, as shown in Figure 11. If the Styrofoam piece is not floating evenly, you can try taping the test leads onto the rim of the mixing bowl to keep things in place.
The pump may start running as soon as you put the conductivity sensor in the neutralized solution, but do not worry if the pump is not running yet. Remember that a potentiometer is a variable resistor; you can change its resistance by turning the white knob. Once the pump is running, very slowly turn the potentiometer's knob in the opposite direction to turn the pump off. While you are adjusting the potentiometers, identify which pump tube has liquid flowing out of it.
Make sure all of the jumper wires and components are pushed firmly into the breadboard's holes. Make sure no exposed metal parts (like the leads of the resistors) are touching each other, as this will create a short circuit. Be especially careful to avoid creating a short circuit by having wires from the red and blue bus strips touch each other. Once you have normalized your artificial pancreas model so that the pump does not run when the conductivity sensor is in a neutralized solution, carefully remove the conductivity sensor from the neutralized solution (leaving the pump's tubes in the "Vinegar" bowl), and rinse the sensor briefly with some baking soda solution (over a sink or a different bowl).
Note: Make sure the sensor is floating the same way that it was in the neutralized solution. While the pump is running, carefully and continually move the end of the pump tube in the "Baking Soda" bowl so that the vinegar mixes well with the baking soda solution throughout the bowl (including under and around the sensor).
When the pump stops, measure how much vinegar solution is left in the "Vinegar" bowl by carefully pouring it into a metric measuring cup or a graduated cylinder using a funnel. Note: There may be more liquid in the bowl than can fit in the measuring cup or graduated cylinder, so you may need to fill it up (and empty it out) multiple times to measure the total amount of baking soda. Since the baking soda solution you prepared is at the same concentration as the vinegar, they should make a neutralized solution when the same amount of each have been mixed together.
Note: Because pH reactions occur on a logarithmic scale, the error measurements can be on a logarithmic scale, too. What could you physically change about your circuit, conductivity sensor, or experimental setup?
Clean and dry the mixing bowls and repeat steps 1–18 to test your model again, with the changes you decided on in step 19, and analyze its results. You can make a bar graph of your results, with a bar for each time you tested the model (labeled on the x-axis) that shows how much vinegar remained when testing each time (labeled on the y-axis in mL). Following the indicator color change of your solutions, you can analyze the pH results as well. How did the pH, or the indicator color, of the vinegar solution change by the addition of the baking soda? Was the indicator color (pH) of the original neutralized solution the same as the indicator color (pH) of the solution when the pump stopped running?
Tip: You may want to refer to the Introduction in the Background tab to help you answer this last question.
In the testing you did for this project, you should have found that the artificial pancreas model could be automated for the part you tested.
Some people may want an artificial pancreas to turn on and pump insulin when they have a specific, different blood glucose level compared to other people. How could you use the artificial pancreas model you made in this project to model the delivery of other types of medicines?
How could you make the artificial pancreas model used in this project more similar to what a real artificial pancreas would be like? For an advanced chemistry challenge, instead of the chemical reaction used in the artificial pancreas model in this project, you could try using a different chemical reaction. You could look into doing a titration (which is typically a color-changing reaction that depends on the exact chemicals involved). Alternatively, instead of bromothymol blue as an indicator you could use cabbage juice, which also changes color based on the pH of the solution. For science projects on measuring sugars in foods and relating this to diabetes, see How Sweet It Is!
Compared to a typical science class, please tell us how much you learned doing this project.
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Beta-Cell Function and FailureSoltani Nepton1[1] Physiology Department, Faculty of Medicine, Hormozgan University of Medical Science, Iran1. Russ HA, Sintov E, Anker-Kitai L, Friedman O, Lenz A, Toren G, Farhy C, Pasmanik-Chor M, Oron-Karni V, Ravassard P, Efrat S.
Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q. People are most familiar with the three major cells in blood: red blood cells, white blood cell and platelets.
92% of plasma is made up of water mixed with a number of important substances and nutrients such as hormones, immunoglobulins, lipoproteins, mineral ions, and gases. Research has shown that green tea can help prevent the peroxidation of lipids and the rupturing of red blood cells.
Although cholesterol is one of the essential substances necessary for the normal function of a human body, excessive level of cholesterol, or more precisely, excessive level of LDL may have a severe impact on blood vessels and eventually on human health. Green tea has been shown to be beneficial by lowering blood choleterol levels, including total cholesterol and further decrease of LDL levels. Diabetes is a condition of having too much sugar in blood, which may be due to a lack of insulin or problems with insulin sensitivity. Lack of physical activity and obesity are the biggest causes of diabetes in that they may lead to insulin resistance and an eventual lack of insulin production in the long run.
Many studies show that drinking green tea increases the sensitivity of insulin, which means our bodies can recognize insulin better. High blood pressure, which may be due to excessive levels of cholesterol and sugar and other related factors, is considered as one of the major risk factors of developing cardiovascular diseases such as a heart attack and stroke. Long-term untreated high blood pressure may damage blood vessels and eventually damage organs such as the kidney, stomach and intestines. A lifestyle of regular green tea consumption has been associated with lowering blood pressure.
One area in which that motivation is readily apparent is in the field of biomedical engineering, where an intense focus of research right now is on creating better insulin pumps and an artificial pancreas. See Figure 1 for typical blood glucose level fluctuations for a person over the course of a day. This graph shows how a person's blood glucose levels may change over the course of a day, and how eating a meal with lots of sugar (sucrose) can affect blood glucose levels. The level of glucose in your blood is regulated by insulin, a hormone made by the pancreas. If left untreated, the blood glucose levels of a person with type 1 diabetes could be dangerously high, which is a condition called hyperglycemia. And having blood glucose levels that are too high (hyperglycemia), or too low (hypoglycemia), can cause serious health problems. Diabetics who take insulin supplements take them in the form of insulin injections (using a needle) or infusions using an insulin pump, like the one shown in Figure 2. This picture shows an insulin pump attached to a person's body to infuse specific amounts of insulin. In this project, you will get to find out by building a simplified model of an artificial pancreas system and investigating the challenges of getting such a device to work.
This flowchart shows how an artificial pancreas would work (on the left) and how those steps are similar to what is done in the model used in this project (on the right). A solution of vinegar (acetic acid, or CH3COOH), which is an acid, will represent high blood glucose levels, and a solution of baking soda (sodium bicarbonate, or NaHCO3), which is a base, will represent insulin. It has to do with the fact that acidic solutions are fairly conductive, which means that they can conduct electricity, or allow electrical current to flow through them. A transistor is an electrical component that acts like a switch; if the transistor receives a high enough voltage, it can allow electrical current to travel through a different path of the circuit. It's not as smart as you are, and it may occasionally give humorous, ridiculous, or even annoying results!
We recommend purchasing the exact parts from Jameco, listed below, unless you are confident that you can find appropriate parts with equivalent specifications. Because of this, you will need a pair of scissors that you do not mind denting, or you could use a pair of wire cutters. If you have never used a breadboard before, you should refer to the Science Buddies reference How to Use a Breadboard before you proceed.
The sensor will be made using bare copper wire, a straw, scissors, and a small piece of flat Styrofoam. Note: Cutting the wire with scissors may dent the scissors, so use a pair of scissors that may be alright to dent, or use a pair of wire cutters.
If the wires move much, they could change the amount of conductivity detected by the sensor. Wrap the ends of two copper wires around a segment of straw, making about four loops with each wire. Make sure the bend is sharp enough to keep the wires from sliding down through the Styrofoam. Because of this, it is important that the amount of wire submerged in the liquid is always the same.
After attaching the alligator clips to the copper wires, the conductivity sensor should look like the one here. You will do this by first normalizing it to a neutralized solution to make sure the pump will turn off once your solution is neutralized.
You must pour the vinegar into the bowl very slowly to give the two solutions time to slowly react, otherwise you may end up with a big mess and will need to make up fresh solutions! Final colors of the vinegar, baking soda solution and neutralized solution according to the bromothymol blue indicator color scale. Place the conductivity sensor in the neutralized solution so that the Styrofoam piece floats and the straw part with wrapped wire is submerged.
When you are equilibrating the artificial pancreas circuit in a neutralized solution, your setup should look like this one.
Try turning it all the way clockwise and all the way counter-clockwise find out which way turns the pump on (which way you need to turn it will depend on which way you put the potentiometer into the breadboard).


Stop turning the knob when it reaches the point that makes the pump very slow and almost turn off. When the pump is not running, dry the end of this tube and mark it with a small dot using a permanent marker. Note that the transistor may become warm while the pump is running, but it should not become dangerously hot. This can make the circuit get dangerously hot and can even melt some of the plastic components.
If needed, tape the alligator clip test leads to the side of the bowl to hold them in place so that the Styrofoam piece is floating evenly.
When you are neutralizing the baking soda solution with vinegar, this is what the setup should look like. It is very important to have all of the vinegar and baking soda mixed well together to neutralize the baking soda solution. If this happens, the conductivity sensor may still detect a basic solution, even though parts of the solution in the bowl have been completely neutralized (or may even be acidic). For example, could you improve the stability of your sensor if it was moving around, or build a new sensor with some changes to the design? For example, if you find that mixing is a problem in your procedure, try different ways to increase the mixing of both solutions, starting by stirring them with a spoon, swirling them or even using the conductivity sensor to stir the solution.
You can draw a horizontal line across the graph at the "100 mL" point to show the ideal amount of vinegar left.
In other words, when the solution is very basic (representing high blood glucose levels), the pump turns on and adds an acidic solution (representing insulin) to neutralize the solution (representing normal blood glucose levels). You could try modeling this by making solutions with different amounts of baking soda solution and vinegar mixed together (instead of equal amounts, as you use in this project) and then normalize the artificial pancreas model to the different solutions, one at a time (each one representing a different person). A Science Buddies project idea that uses the titration method is Which Orange Juice Has the Most Vitamin C?
For information on how to make this pH indicator solution, check out the Science Buddies project idea Cabbage Chemistry.
Prevention of beta cell dysfunction and apoptosis by adenoviral gene transfer of rat insulin-like growth factor 1. ICV brain glibenclamide suppresses counterregulatory responses to brain glucopenia in rats: evidence for a role for brain KATP channels in hypoglycemia sensing. The function of CA(2+) channel subtypes in exocytic secretion: new perspectives from synaptic and non-synaptic release.
Prevention of beta cell dysfunction and apoptosis activation in human islets by adenoviral gene transfer of the insulin-like growth factor I. Beta-cell dysfunction and insulin resistance in type 2 diabetes: role of metabolic and genetic abnormalities. Effect of the administration of Psidium guava leaves on lipid profiles and sensitivity of the vascular mesenteric bed to phenylephrine in STZ-induced diabetic rats.
Insulin-Producing Cells Generated from Dedifferentiated Human Pancreatic Beta Cells Expanded In Vitro. Each component plays a significant role in the human body, but one must understand that the other half of blood (55%) is composed of plasma. While each component of the blood has its own role, the role of the blood itself is to circulate through out the body as it carries various components to proper locations of the body.
Notable compounds include catechins, theanine, vitamins, essential oil, minerals and caffeine.
These studies examined the antioxidants in the blood, the evidence of lipid peroxidation, and changes in the membrane of red blood cells caused by oxidation in order to see how green tea might affect the oxidation of blood plasma and red blood cells. The oxidation of LDL particles can cause the formation of atherosclerotic lesions, which is the thickening of artery walls caused by the accumulation of fatty materials under the blood vessel wall. In addition, drinking green tea has been shown to lower glucose production in the liver and decrease glucose absorption in the intestines.
Catechins in green tea have been shown to dilate and relax the blood vessels, which can lower blood pressure. Symptoms include blurry vision, excessive thirst, fatigue, frequent urination, hunger and weight loss.
Be very careful with your wiring to prevent short circuits from happening; short circuits can get very hot and cause plastic parts of the circuit to melt. When blood glucose levels rise after eating a meal, the pancreas releases insulin, which causes cells in the body (such as liver, muscle, and fat cells) to take up glucose, removing it from the blood and storing it (as glycogen) to use for energy later. This leaves many type 1 diabetes patients constantly checking their blood glucose levels, calculating how their actions will change their levels, and adjusting their insulin doses to avoid a critical high or low.
However it is a done, currently a person who takes insulin must closely monitor his or her blood glucose levels to determine when, and how much, insulin to take.
The video will give you a basic understanding of the goals of an artificial pancreas and the path to making one, but because this is a rapidly progressing field, you should do your own internet search to see what the current status of the research is. Clearly, blood, insulin, and glucose are not readily available for a science project, but you can use other components to mimic some of the interactions and start designing and fine-tuning a model of an artificial pancreas.
When acids and bases (like vinegar and baking soda, respectively) are mixed, a chemical reaction occurs (shown in Equation 1) that produces water (H2O) and bubbles of carbon dioxide gas (CO2). In the circuit you will build for this project, the transistor will be connected to a pump so that when enough current flows through the conductivity sensor, it outputs a high voltage to the transistor, which allows current to flow through the pump and make it run.
The conductivity sensor and the potentiometers together make up what is called a voltage divider, and this is technically what lets the conductivity sensor send the high voltage to the transistor to make the pump turn on.
When the solution has a neutral pH, the sensor outputs a low voltage, so the transistor does not let any current flow through the pump. How are the challenges encountered when making this model similar to the challenges that engineers who are trying to make a real artificial pancreas system would face?
You can follow a step-by-step slideshow that will show you how to put components in the breadboard one at a time. Since Styrofoam floats, the Styrofoam piece will help keep the wires submerged at the same depth in the liquid for your tests. The vinegar should turn yellow, the baking soda solution blue and the neutral solution green.
In this step, you will normalize your artificial pancreas model so that the pump does not run in a neutralized solution, but still runs in a solution that is slightly more acidic (which will be more conductive). If it is very hot, or if you notice any smoke or a burning smell, this probably means that you have a short circuit. The pump should start running, pumping vinegar (a drop or a few drops at a time) into the bowl with baking soda solution, and you should see bubbles being made as the acid-base reaction takes place.
It is very important to make sure that the sensor is submerged in the liquid to the same depth that it was in the neutralized solution or your results may be inaccurate. You will see that at the spot where vinegar drips into the baking soda solution, the color of the indicator will change from blue to yellow. How does the color of the indicator (the pH) now compare to the pH of the neutralized solution you made in step 7? Note that changing the concentration of the baking soda solution will also change the amount of vinegar that you need to neutralize this solution.
How are the challenges you faced in designing this model similar, and different, to the challenges faced in designing a real, accurate artificial pancreas? However, you did not test how the model works for other parts of an artificial pancreas, such as continuing to add insulin when the blood glucose levels are consistently high over time. For some ideas, check out the Science Buddies science project idea Electrolyte Challenge: Orange Juice Vs. Beta cells (?-cells)Beta cells are a type of cell in the pancreas located in the so-called islets of Langerhans. Program and abstracts of the 62nd Scientific Sessions of the American Diabetes Association, 14(18), 2002; San Francisco, California. Program and abstracts of the 62nd Scientific Sessions of the American Diabetes Association, 17, 2002; San Francisco, California. Program and abstracts of the 62nd Scientific Sessions of the American Diabetes Association, 14(18), 2002, San Francisco, California. Effect of oral magnesium sulfate administration on blood pressure and lipid profile in streptozocin diabetic rat.Eur J Pharmacol. The lungs work to provide oxygen to blood, the liver works to remove toxic materials from the blood, the kidneys filter blood to remove toxins in the blood, and the organs of the digestive system work to provide nutrients to the blood. Catechins (tea polyphenols) act as antioxidants by scavenging reactive oxygen species (ROS) in the blood. Lipid peroxidation occurs when oxidation in the blood steals away electrons from the lipids in red blood cell membranes, weakening them. Antioxidants in green tea may reduce free radical damage to blood vessels and help maintain the normal function of blood vessels. Such devices would help eliminate the procedures that a person living with diabetes has to do, as well as remove the nearly constant health decisions they have to make. Both table sugar (sucrose) and other types of carbohydrates, such as starch (found in large quantities in pasta and other grain-rich foods), are broken down by our bodies to make glucose. When the blood glucose levels start falling, the pancreas stops releasing insulin, and the stored glucose is used for energy. Insulin pumps are typically small, about the size of a cell phone, and the system usually includes a continuous glucose sensor that detects the amount of glucose in the person's blood and an electronic interface that is told how much insulin to give to the person. Because of this conductive difference, an electrical sensor can be made that can detect if a solution is acidic or neutral. For a detailed explanation of how the circuit works, including a circuit diagram, see the FAQ section. When the solution has a high pH, the sensor outputs a high voltage, which activates the transistor, causing current to flow through the pump, which then pumps liquid.
This lets you make coarse, medium, and fine adjustments respectively to the total resistance value. Immediately disconnect the battery pack from the breadboard, and make sure that everything else is connected correctly by referring to the diagrams above.
The color change of the solution gives you an indication of what the pH of the solution in the "Baking Soda" bowl is during neutralization. Try adding more baking soda solution to the "Baking Soda" bowl after it is neutralized; does it turn the pump back on again? They make up 65-80% of the cells in the islets.The Islets diameter is about 50 to 300 micrometers. Program and abstracts of the 62nd Scientific Sessions of the American Diabetes Association; 14(18), 2002, San Francisco, California. Extracts on insulin release from in situ isolated perfused rat pancrease in newly modified isolation method: the role of Ca and K channels.
LDL particles that oxidize inside the wall of the artery can begin a cycle of cell damage and inflammation. Specifically, the devices would help people with diabetes control how much sugar is in their blood. If blood glucose levels get too low, the pancreas may produce glucagon, a hormone that increases the levels. To see what it is like to use an insulin pump and continuous glucose sensor to manage type 1 diabetes, you can check out the video in the article by D. For a refresher on these topics, see the Science Buddies page on Acids, Bases, & the pH Scale. Keep in mind that this is not the reaction that occurs when insulin is added to change the blood glucose levels in a person! Specifically, in the artificial pancreas model you build in this project, a conductivity sensor is made from two metal wires (or electrodes) that are a certain distance apart in the solution. You can also read more about basic electricity concepts in the Science Buddies Electricity, Magnetism, & Electromagnetism Tutorial.
When you change the total resistance of the potentiometers, this affects how much voltage is sent to the transistor, which controls whether the pump is turned on or not.
Play around with adjusting the knobs of all three potentiometers until you are satisfied that the pump does not run in the neutralized solution (but will still run if turned slightly). It is a daunting goal; the pancreas has a very complex biological role that has to be mimicked by a combination of electronics, chemistry, and biology.
This process is how the pancreas and the hormones it produces are in charge of regulating blood glucose levels. A conductivity sensor will represent the glucose sensor, and control whether a pump in the electrical circuit turns on or not. You are using these chemicals as substitutes in your model since baking soda and vinegar are easy-to-obtain household materials. The more conductive the solution is, the more electrical current can flow through it from one electrode to the other.
If you want to find out more about how this works (it involves forming a voltage divider with the conductivity sensor), try re-reading the Introduction in the Background tab and check out the FAQ section in the Help tab.
Remember to make sure that the exposed metal parts of different components, like the resistors and alligator clips, are not bumping into each other, as this will also create a short circuit. By blocking lipid peroxidation, the catechins in green tea can prevent red blood cell membranes from being damaged by oxidation and keep red blood cells healthy and strong. Studies have shown that antioxidants in green tea can bind with the oxygenated molecules in blood, which prevents them from reacting with the LDL.
This project will allow you to explore some of the complexities engineers and scientists face as they strive to create an artificial pancreas. Watch this video to see how blood glucose levels can change over time for different people.
When the solution is very acidic, the conductivity sensor will make the electrical circuit run a pump. You could measure the amounts of baking soda and vinegar that are added over time and graph your results.
These cells are surrounded by alpha cells that secrete glucagon, smaller numbers of delta cells that secrete somatostatin, and PP cells or F cells that secrete pancreatic polypeptide. This prevents the oxidation of LDL, thereby reducing the possibility of damage to blood vessels. The pump will move a basic solution, which represents insulin, into the acidic solution to neutralize it. All of the cells communicate with each other through extracellular spaces and through gap junctions. When the acidic solution becomes more neutralized, the conductivity sensor will make the circuit stop powering the pump. This arrangement allows cellular products secreted from one cell type to influence the function of downstream cells. This represents high blood glucose levels being lowered by the addition of insulin, until the glucose levels are normal and no more insulin needs to be added to the bloodstream.
As an example, insulin secreted from beta cells can suppress glucagon secretion.A neurovascular bundle containing arterioles and sympathetic and parasympathetic nerves enters each islet through the central core of beta cells.
Figure 3 helps summarize the important information, and shows how the artificial pancreas model you will make in this project is similar to, and different from, a real artificial pancreas.
The arterioles branch to form capillaries that pass between the cells to the periphery of the islet and then enter the portal venous circulation.2.


Beta cells functionsInsulin is synthesized as preproinsulin in the ribosomes of the rough endoplasmic reticulum in the beta cells (fig 1). Preproinsulin is then cleaved to proinsulin, which is transported to the Golgi apparatus where it is packaged into secretory granules located close to the cell membrane.
Proinsulin is cleaved into equimolar amounts of insulin and C-peptide in the secretory granules. The process of insulin secretion involves fusion of the secretory granules with the cell membrane and exocytosis of insulin, C-peptide, and proinsulinInsulin is a hormone that controls the blood glucose concentration. The liver maintains the base-line glucose level, but the beta cells can respond quickly to spikes in blood glucose by releasing some of its stored insulin while simultaneously producing more. The response time is very quick.Figure 1Mouse pancreatic islet as seen by light microscopy. Glucagon is labeled in red and the nuclei in blueApart from insulin, beta cells release C-peptide, a consequence of insulin production, into the bloodstream in equimolar amounts. Amylin's metabolic function is now somewhat well characterized as an inhibitor of the appearance of nutrient [especially glucose] in the plasma. Whereas insulin regulates long-term food intake, increased amylin decreases food intake in the short term.GABA (? amino butyric acid) is produced by pancreatic beta cell. GABA released from beta cells can act on GABA Areceptor in the ? cells, causing membrane hyperpolarization and hence suppressing glucagon secretion.
An impaired insulin-Akt-GABAA receptors glucagon secretory pathway in the islet may be an underlying mechanism for unsuppressed glucagon secretion, despite hyperglycemia, in diabetic subjects. Some studies demonstrated that beta cells also express GABA A receptors, forming an autocrine GABA signaling system.
However, the role of this autocrine GABA signaling in the regulation of beta cell functions remains largely unknown. Zinc can keep insulin molecules together in the beta cells.Beta cells must have zinc to function.
Mechanisms of insulin secretion from beta cellsThe secretion of insulin from pancreatic beta cells is a complex process involving the integration and interaction of multiple external and internal stimuli. Thus, nutrients, hormones, neurotransmitters, and drugs all activate or inhibit insulin secretion. The primary stimulus for insulin release is the beta-cell response to changes in glucose concentration.
First-phase insulin release occurs within the first few minutes after exposure to an elevated glucose level; this is followed by a more permanent second phase of insulin release.
Of particular importance is the observation that first-phase insulin secretion is lost in patients with type 2 diabetes. In the K (ATP) channel-dependent pathway, glucose stimulation increases the entry of extrinsic Ca2+ through voltage-gated channels by closure of the K (ATP) channels and depolarization of the beta cell membrane. While in the GTP-dependent pathway, intracellular Ca2+ is elevated by GTP-dependent proteins and augments the Ca2+-stimulated release. Secretagogues and insulin secretion inhibitors act at intermediate steps of these signaling pathways and influence the process of insulin exocytosis. Several researchers have investigated this intricate mode of known secretagogue action using isolated islets as an in vitro model. To quote a few; imidazoline antagonists of alpha 2-adrenoreceptors increase insulin release in vitro by inhibiting ATP-sensitive K+ channels in pancreatic beta cells. Some researchers have evaluated the properties of sulphonylurea receptors (SUR) of human islets of Langerhans. They studied the binding affinity of various oral hypoglycaemic agents to the receptor and also tested insulinotropic action of the drugs on intact human islets. This binding potency order was parallel with the insulinotropic potency of the evaluated compounds. Some investigators have shown an insulinotropic effect of Triglitazone (CS-045) and have shown its mode of action to be distinct from glibenclamide (a sulphonylurea drug). A-4166, a derivative of D-phenylalanine, evokes a rapid and short-lived hypoglycaemic action in vivo. Some studies showed S21403, a meglitinide analogue to be a novel insulinotropic tool in the treatment of type 2 diabetes, as it affected cationic fluxes and the drugs secretary responses displayed favourable time course of prompt, and not unduly prolonged, activation of beta cells.
Some studies demonstrated that tetracaine (an anaesthetic) stimulates insulin secretion by release of intracellular calcium and for the first time elucidated the role of intracellular calcium stores in stimulus-secretion coupling in the pancreatic beta cells.
JTT-608, is a nonsulphonylurea oral hypoglycaemic agent which stimulates insulin release at elevated but not low glucose concentrations by evoking PKA-mediated Ca2+ influx.4. The importance of KATP channelsThe KATP channels play an integral role in glucose-stimulated insulin secretion by serving as the transducer of a glucose-generated metabolic signal (ie, ATP) to cell electrical activity (membrane depolarization).
Thus, like neurons, beta cells are electrically excitable and capable of generating Ca2+ action potentials that are important in synchronizing islet cell activity and insulin release.
In addition to being signal targets for glucose, KATP channels are the targets for sulfonylureas, which are commonly prescribed oral agents in the treatment of type 2 diabetes. The sulfonylurea receptor belongs to a superfamily of ATP-binding cassette proteins and contains the binding site for sulfonylurea drugs and nucleotides.
Evans, MD, Yale University Medical School, New Haven, Connecticut, and colleagues have suggested that glucose sensing in the brain during hypoglycemia may be mediated by KATP channels located in brain hypothalamic neurons. Thus, these molecules may also serve as new therapeutic targets for the restoration of impaired hypoglycemia awareness and glucose counterregulation in type 1 diabetes.5. Voltage-dependent Ca2+ channels: Novel regulatorsExtracellular Ca2+ influx through L-type voltage-dependent Ca2+ channels (VDCC) raises free cytoplasmic Ca2+ levels and triggers insulin secretion.
The structure of the VDCC is complex and consists of 5 subunits: alpha1, alpha2, beta, gamma, and delta units. The alpha subunit constitutes the ion-conducting pore, whereas the other units serve a regulatory role. Previous work has identified that isoforms of alpha1 subunits interact with exocytotic proteins.
More recently, using the yeast hybrid screening method, a novel protein, Kir-GEM, interacting with the beta3 isoform of the VDCC, has been identified by Seino and colleagues.
Furthermore, it has been determined that Kir-GEM inhibits alpha ionic activity and prevents cell-surface expression of alpha subunits. The investigators have proposed that in the presence of Ca2+, Kir-GEM binds to the beta isoform, and this interaction interferes in the trafficking or translocation of alpha subunits to the plasma membrane. Novel cAMP signaling pathways of insulin releaseThe incretins are another set of factors that are important hormonal regulators of insulin secretion. The incretins are polypeptide hormones released in the gut after a meal that potentiate insulin secretion in a glucose-dependent manner. Due to their dependence on ambient glucose for action, they are emerging as important new therapeutic agents to promote insulin secretion without accompanying hypoglycemia (a common complication of sulfonylurea treatment).Unlike sulfonylureas, incretins act by activating Gs (a G-protein that activates adenylyl cyclase) to increase cAMP in beta cells. Typically, the main mechanism of action of cAMP is by activation of an enzyme called protein kinase A (PKA) that, in turn, phosphorylates other substrates to turn on (or off) vital cell functions. Then, using molecular reagents that antagonize the effects of cAMPS, they observed that incretin-potentiated insulin secretion is attenuated. These results provide a mechanism whereby cAMP can directly promote exocytosis of insulin granules without activation of PKA (ie, a PKA-independent pathway), and thereby provide additional molecular targets for therapeutic intervention.7. Beta cell dysfunction and apoptosisType one diabetes: Islet beta-cells are almost completely destroyed when patients with type 1 diabetes are diagnosed. In the absence of a defect in beta-cell function, individuals can compensate indefinitely for insulin resistance with appropriate hyperinsulinemia, as observed even in obese populations. However, when allowance is made for the hyperglycaemia and the fact that glucose stimulates insulin secretion, it becomes apparent that the insulin levels in diabetic patients are lower than in healthy controls and inadequate beta-cell function therefore represents a key feature of the disease. Theoretically, the insulin secretory defect could result from either defects of beta-cell function or a reduction in beta-cell mass. Most quantitative estimates indicate that type 2 diabetes associates with either no change or < 30% reduction in beta-cell mass. Moreover, the secretion defect is more severe than can be accounted for solely by the reduction in beta-cell mass. It therefore appears that the insulin secretory defect in type 2 diabetes does not primarily result from insufficient beta-cell mass but rather from an impairment of insulin secretion.8. Prevention of beta cell dysfunction and apoptosis Islet beta-cells are almost completely destroyed when patients with type 1 diabetes are diagnosed.
The cure of type 1 diabetes requires beta-cell regeneration from islet cell precursors and prevention of recurring autoimmunity. Therefore, beta-cell replacement, regeneration and proliferation emerge as a new research focus on therapy for type 1 diabetes; however, its application is limited by the shortage of pancreas donors. In-vitro expansion of human cadaveric islet beta cells represents an attractive strategy for generation of abundant beta-like cells. Human beta cells patent a very low proliferation capacity in vivo, and intact isolated islets cultured in suspension do not proliferate, although they remain functional for months. When islets are allowed to attach, limited replication of beta cells can be induced by growth factors or extracellular matrix components before the beta-cell phenotype is lost.
Previous accepting of the determinants of tissue mass during adult life is still rudimentary. Insights into this problem may suggest novel approaches for the treatment of neoplastic as well as degenerative diseases. In the case of the pancreas, elucidating the mechanisms that govern ? cell mass will be important for the design of regenerative therapy for both type 1 and type 2 diabetes, diseases characterized by an insufficient mass of ? cells. It is clear that ? cell mass increase during pregnancy and in insulin-resistant states, but evidence on the ability of ? cells to regenerate from a severe, diabetogenic injury is conflicting. Igf1 has been shown to influence ?-cell apoptosis, and both Igf1 and Igf2 increase islet growth; Igf2 does so in a manner additive with fibroblast growth factor 2.
Some study showed that IGF-1 can protect beta-cells from the destruction of apoptosis factors and promoting beta-cell survival and proliferation.
Interleukin-1beta (IL-1 beta) is a potent pro-inflammatory cytokine that has been shown to inhibit islet beta cell function as well as to activate Fas-mediated apoptosis in a nitric oxide-dependent manner.
Furthermore, this cytokine is effective in recruiting lymphocytes that mediate beta cell destruction in type one diabetes. IGF-I has been shown to block IL-1beta actions in vitro.Glucagon like peptide 1 (GLP-1) is a potent insulin secretagogue released by L-cells of the distal large intestine in response to meal ingestion and, together with glucose-dependent insulinotropic polypeptide (GIP), account for 90% of the incretin effect. GLP-1 also inhibits glucagon secretion, delays gastric emptying, and promotes weight loss by its appetite-suppressant effect.
GLP-1 analogs also stimulate islet neogenesis and ?-cell replication and inhibit islet apoptosis. The gluco-incretin hormones GLP-1 and GIP can protect beta-cell against apoptosis induced by cytokines or glucose and free fatty acids.
Increases in cAMP levels, for instance as stimulated by GLP-1 or GIP action, potentiate glucose-stimulated insulin secretion by both protein kinase A (PKA)-dependent and independent mechanisms; they also stimulate gene transcription through PKA dependent phosphorylation of the transcription factor CREB. Studies of mice with beta-cell specific inactivation of either receptor indicated that the insulin receptor was important for compensatory growth of the beta-cells in response to insulin resistance whereas the IGF-1 receptor was involved in the control of glucose competence. GLP-1 enhances beta cell function with an increase in the ability to secrete insulin and restore first phase insulin release.
Within the pancreas, GLP-1 expands ?-cell mass via promotion of ?-cell growth and reduction of ?-cell death.?-Aminobutyric acid (GABA), a prominent inhibitory neurotransmitter, is present in high concentrations in ?-cells of islets of Langerhans. The GABA shunt enzymes, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T) have also been localized in islet ?-cells. With the recent demonstration that the 64,000-Mr antigen associated with insulin-dependent diabetes mellitus is GAD, there isincreased interest in understanding the role of GABA in islet functions. Only a small component of ?-cell GABA is contained in insulin secretory granules, making it unlikely that GABA, co-released with insulin, is physiologically significant. Our immunohistochemical study of GABA in ?-cells of intact islets indicates that GABA is associated with a vesicular compartment distinctly different from insulin secretory granules. Physiological studies on the effect of extracellular GABA on islet hormonal secretion have had variable results. The most compelling evidence for GABA regulation of islet hormone secretion comes from studies on somatostatin secretion, where it has an inhibitory effect. Some researchers present new evidence demonstrating the presence of GABAergic nerve cell bodies at the periphery of islets with numerous GABA-containing processes extending into the islet mantle. This close association between GABAergic neurons and islet ?- and ?-cells strongly suggests that GABA inhibition of somatostatin and glucagon secretionis mediated by these neurons.
New evidence indicates that GABA shunt activity is involved in regulation of insulin secretion. These new observations provide insight into the complex nature of GABAergic neurons and ?-cell GABA in regulation of islet function. Our study showed that GABA exerts has protective and regenerative effects on islet beta cells and reverses diabetes. GABA therapy increased beta cell proliferation and decreased beta cell apoptosis, which in turn increase beta cell mass and induced the reversal of hyperglycemia in the different kind of mice. Our data suggest that GABA exerts has ani-inflammatory effects, and is directly inhibitory to T cells and macrophages.Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of the diabetic complications. Photochemical analysis of those herbs have revealed the presence of flavonoids, which include quercetin and its derivatives. It is concluded that quercetin, a flavonoid with antioxidant properties brings about the regeneration of the pancreatic islets and probably increases insulin release in streptozocin-induced diabetic rats.Connective tissue growth factor (CTGF), to induce adult ? cell mass expansion. Some study showed that CTGF is required for embryonic ? cell proliferation3, and that CTGF overexpression in embryonic cells increases ? cell proliferation and ? cell mass.
The mouse pancreas develops from ventral and dorsal evaginations of the posterior foregut endoderm at embryonic day, a process dependent on the transcription factors Pdx1 and Ptf1.
Differentiation of all pancreatic endocrine cell types (?, ?, ? and PP) is dependent on the transcription factor, neurogenin 3 (Ngn3).
Ngn3 expression is controlled by a variety of factors, including the Notch signaling pathway and the transcriptional regulators pancreatic and duodenal homeobox 1 (Pdx1), SRY-box 9 (Sox9) and hepatic nuclear factor 6 (Hnf6). Although ? cell neogenesis begins, these early insulin-positive cells do not contribute to mature islets.
Instead, endocrine cells that will go on to contribute to the mature islets begin to differentiate period known as the secondary transition. Although several factors have been identified that play a role in the regulation of embryonic and neonatal ? cell proliferation.
One cell cycle regulator that does play a role in embryonic ? cell proliferation is the cell cycle inhibitor, p27Kip1. Inactivation of p27Kip1 during embryogenesis results in an increase in ? cell proliferation and subsequently ? cell mass. There was no change, however, in early postnatal ? cell proliferation, suggesting that p27Kip1 is not crucial to postnatal proliferation.As mentioned above Pdx1expressed in multipotent pancreatic progenitors in the early stages of pancreas development, but, Pdx1 expression becomes enhanced in insulin-positive cells and is found at only low levels in exocrine cells. This expression pattern is maintained into adulthood and Pdx1 plays a critical rolein maintenance of the mature ? cell phenotype. Inactivation of Pdx1 in embryonic insulin-expressing cells results in a dramatic decrease in ? cell proliferation at late gestation, leading to decreased ? cell mass at birth and early onset diabetes.



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Comments

  1. 06.11.2014 at 15:21:17


    Called a carrier-mediated system??which consists of small protein high blood glucose levels for and crackers.

    Author: barawka
  2. 06.11.2014 at 14:49:36


    Insulin, with hypoglycemia as a possible side dropping dangerously.

    Author: Tenha_qizcigaz