It’s well known that a stress-filled lifestyle can lead to high blood pressure, insomnia and a host of other chronic health issues. Past studies have partly linked stress with the onset of diabetes, but the mechanisms behind why this happens were poorly understood. Many of us, faced with a decision about our medical treatment, wish we had a crystal ball to consult.
Type 2 diabetes, the most common kind, results from too little insulin in the bloodstream, leading to high blood sugar levels and a host of other health problems. Good news for diabetics: Last week the FDA approved an artificial pancreas device that could automate the arduous process of blood sugar regulation. In what seems a weird twist of fate, infants who are undernourished are more likely to grow up to have metabolic disorders such as cardiovascular disease and type 2 diabetes—conditions usually associated with obesity. Most researchers currently believe the connection between undernourishment and metabolic disease is a case of adaptation gone wrong.
But then, what happens to undernourished kids who grow up and experience famine as an adult too?
However a study of two preindustrial Finnish towns finds that the exact opposite appears to have taken place. For those with type 1 diabetes, low blood sugar can translate to a lack of energy during the day. Researchers equipped 247 diabetic participants with sensors that constantly monitored their blood sugar levels. During the three-month trial, participants with smart pumps experienced a third fewer episodes of hypoglycemia than those with the regular pumps. Researchers have discovered a hormone that triggers the production of insulin-producing cells in mice, a development that could lead to better diabetes treatments in the future.
Daily insulin shots are a direct, if short-term, way to treat the disease, but researchers at Harvard think they may be onto an even more promising solution: boosting beta cells. The production process begins with a straw-like tube of modified gelatin called a hydrogel. This is filled with fibers made of natural proteins like collagen and fibrin, which are part of the extracellular matrix that gives animal cells their structure. D-briefBriefing you on the must-know news and trending topics in science and technology today.
In 1869 Paul Langerhans, a medical student in Berlin, was studying the structure of the pancreas under a microscope when he noticed some previously-unidentified cells scattered in the exocrine tissue.
Over the next two decades, several attempts were made to isolate the secretion of the islets as a potential treatment. Computer-generated image of insulin hexamers highlighting the threefold symmetry, the zinc ions holding it together, and the histidine residues involved in zinc binding. Macleod saw the value of the research on his return from Europe, but demanded a re-run to prove the method actually worked.
Macleod and Banting were awarded the Nobel Prize in Physiology or Medicine in 1923 for the discovery of insulin. Mechanisms which restore satisfactory blood glucose levels after hypoglycemia must be quick, and effective, because of the immediate serious consequences of insufficient glucose (in the extreme, coma, less immediately dangerously, confusion or unsteadiness, amongst many other effects).
There are special transporter proteins in cell membranes through which glucose from the blood can enter a cell.
Although other cells can use other fuels for a while (most prominently fatty acids), neurons depend on glucose as a source of energy in the non-starving human. Diabetes mellitus – general term referring to all states characterized by hyperglycemia. Type 1 – autoimmune-mediated destruction of insulin producing beta cells in the pancreas resulting in absolute insulin deficiency. There have been attempts to improve upon this mode of administering insulin, as many people find injection awkward and painful.
The central problem for those requiring external insulin is picking the right dose of insulin and the right timing.Physiological regulation of blood glucose, as in the non-diabetic, would be best. Quick-acting, such as insulin lispro -- begins to work within 5 to 15 minutes and is active for 3 to 4 hours.
Short-acting, such as regular insulin -- starts working within 30 minutes and is active about 5 to 8 hours.
Intermediate-acting, such as NPH, or lente insulin -- starts working in 1 to 3 hours and is active 16 to 24 hours.
Long-acting, such as ultralente insulin -- starts working in 4 to 6 hours, and is active 24 to 28 hours, and Insulin glargine or Insulin detemir -- both start working within 1 to 2 hours and continue to be active, without peaks or dips, for about 24 hours. A mixture of NPH and regular insulin -- starts working in 30 minutes and is active 16 to 24 hours. There are reports that some patients abuse insulin by injecting larger doses that lead to mild hypoglycemic states. 1922 Banting and Best use bovine insulin extract in human1923 Eli Lilly produces commercial quantities of bovine insulin1923 Hagedorn founds the Nordisk Insulinlaboratorium in Denmark -- forerunner of Novo Nordisk1926 Nordisk receives a Danish charter to produce insulin as a non profit1936 Canadians D.M. In a new study, researchers provide evidence of a direct link between psychological stress and biological dysfunction. Science is short on crystal balls, but a new study has taken a step toward a different kind of predictive tool: flowcharts through some of the most common diagnoses in Western countries, based on the health records of over 6 million people.
As a result, a person has to carefully monitor her blood sugar levels and regularly inject insulin to keep it under control. A baby undernourished in the womb or in early toddler years, so the thinking goes, is being conditioned for a life of limited food. The theory predicts that, since their early years prepared them for it, those kids would have better odds during later lean years. But if it occurs at night, when a person is sleeping, low blood sugar can lead to a coma, seizure, or even death. Half of the participants wore normal insulin pumps to supply a steady, low dose of insulin. And the number of cases where blood-sugar levels dropped low enough to need medical attention were non-existent in the smart pump group.
Researchers in Tokyo suggest something that resembles injectable strings able to integrate themselves organically into the human system.
The fibers create a life-like microenvironment in which the cells can function and interact with each other just like normal cells would, while the hydrogel protects them from the body’s immune response. Apart from being the primary effector in carbohydrate homeostasis, it has effects on fat metabolism and it can change the liver's ability to release fat stores.
The left-hand side is a space-filling model of the insulin monomer, believed to be biologically active. In 1906 George Ludwig Zuelzer was partially successful treating dogs with pancreatic extract, but was unable to continue his work. Several weeks later it was clear the second run was also a success, and he helped publish their results privately in Toronto that November.


Banting, insulted that Best was not mentioned, shared his prize with Best, and MacLeod immediately shared his with Collip.
Production and secretion are largely independent; prepared insulin is stored awaiting secretion. Insulin binds to its receptor (1) which in turn starts many protein activation cascades (2). This is because, at least in the short term, it is far more dangerous to have too little glucose in the blood than too much.
This allows the release of Ca2+ from the ER via IP3 gated channels, and further raises the cell concentration of calcium.Significantly increased amounts of calcium in the cells causes release of previously synthesised insulin, which has been stored in secretory vesiclesThe calcium level also regulates expression of the insulin gene via the calcium responsive element binding protein ( CREB).
In addition some insulin synthesis and release takes place generally at food intake, not just glucose or carbohydrate intake, and the beta cells are also somewhat influenced by the autonomic nervous system. These transporters are, indirectly, under insulin control in certain body cell types (eg, muscle cells). They do not require insulin to absorb glucose, unlike muscle and adipose tissue, and they have very small internal stores of glycogen. Type 2 – multifactoral syndrome with combined influence of genetic susceptibility and influence of environmental factors, the best known being obesity, age, and physical inactivity, resulting in insulin resistance in cells requiring insulin for glucose absorption. Metabolic syndrome – a precondition first called Metabolic Syndrome X by Gerald Reaven, and sometimes called prediabetes. There is research underway to develop methods of protecting insulin so that it can be taken orally, but none has yet reached clinical use. One alternative is jet injection (also sometimes used for vaccinations), which has different insulin delivery peaks and durations as compared to needle injection. Increased blood glucose levels after a meal is a stimulus for prompt release of insulin from the pancreas. Existing pumps can deliver insulin more discreetly than with a syringe, but each dose still has to be programmed manually by the wearer.
A person can’t monitor her blood sugar while sleeping, so levels can drop dangerously low. An artificial pancreas would not only eliminate the need for regular insulin shots during the day but also avoid dangerous episodes of nighttime hypoglycemia. But by the time adulthood rolls around, this production process has slowed down almost to a halt, so that less than one half of one percent of cells are dividing daily.
Scientists’ initial tests of this cell-laden fiber produced working heart, vein and nerve tissues, and even regulated diabetes in living mice.
The researchers tested out ten different kinds of human and rat cells inside the fiber, which organized into their respective 3-D patterns and started doing their jobs. The patent for insulin was sold to the University of Toronto for one dollar.The exact sequence of amino acids comprising the insulin molecule, the so-called primary structure, was determined by British molecular biologist Frederick Sanger. These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).
This homeostatic effect is the result of many factors, of which hormone regulation is the most important.It is usually a surprise to realize how little glucose is actually maintained in the blood, and body fluids.
In healthy individuals these mechanisms are indeed generally efficient, and symptomatic hypoglycemia is generally only found in diabetics using insulin or other pharmacologic treatment. The signalling mechanisms controlling this are not fully understood.Other substances known which stimulate insulin release are acetylcholine, released from vagus nerve endings ( parasympathetic nervous system), cholecystokinin, released by enteroendocrine cells of intestinal mucosa and gastrointestinal inhibitory peptide (GIP). Low levels of circulating insulin, or its absence, will prevent glucose from entering those cells (eg, in untreated Type 1 diabetes). Glycogen stored in liver cells (unlike glycogen stored in muscle cells) can be converted to glucose, and released into the blood, when glucose from digestion is low or absent, and the glycerol backbone in triglycerides can also be used to produce blood glucose. This form of diabetes is strongly inherited.Other types of impaired glucose tolerance (see the diabetes article). It is characterized by elevated blood pressure, dyslipidemia (disturbances in blood cholesterol forms and other blood lipids), and increased waist circumference (at least in populations in much of the developed world). Some diabetics find control possible with jet injectors, but not with hypodermic injection. The increased insulin level causes glucose absorption and storage in cells, reducing glycogen to glucose conversion, reducing blood glucose levels, and so reducing insulin release. In short, if a diabetic closely controls blood glucose levels (ie, on average, both over days and weeks, and avoiding too high peaks after meals) the rate of diabetic complications goes down.
Researchers around the world have thus been striving to perfect an artificial pancreas to automate insulin regulation. When that person grows up and instead has access to ample food (and maybe even an excess of high-calorie junk food as is often the case today), their scaled-back metabolism can’t take it, and the mismatch leads to disease. On testing the urine they found that there was sugar in the dog's urine, demonstrating for the first time the relationship between the pancreas and diabetes.
Scott at the University of Chicago used aqueous pancreatic extracts and noted a slight diminution of glycosuria, but was unable to convince his director and the research was shut down.
Banting suggested that they try to use fetal calf pancreas, which had not yet developed digestive glands; he was relieved to find that this method worked well.
Such hypoglycemic episodes vary greatly between persons and from time to time, both in severity and swiftness of onset. However, more commonly there is a decrease in the sensitivity of cells to insulin (eg, the reduced insulin sensitivity characteristic of Type 2 diabetes), resulting in decreased glucose absorption. Exhaustion of these sources can, either temporarily or on a sustained basis, if reducing blood glucose to a sufficiently low level, first and most dramatically manifest itself in impaired functioning of the central nervous system – dizziness, speech problems, even loss of consciousness, are not unknown. The basic underlying cause is insulin resistance, a diminished capacity for insulin response in some tissues (eg, muscle, fat, liver) to respond to insulin. The intended implication would seem to be that insulin has effects similar to those alleged for some steroids. The rising incidence of metabolic diseases in the developing world today may be partly due to this connection. He was awarded the Nobel Prize in Chemistry in 1958.In 1967, after decades of work, Dorothy Crowfoot Hodgkin determined the spatial conformation of the molecule, by means of X-ray diffraction studies. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one.
In severe cases prompt medical assistance is essential, as damage (to brain and other tissues) and even death will result from sufficiently low blood glucose levels. If blood glucose levels drop lower than this, especially to dangerously low levels, release of hyperglycemic hormones (most prominently glucagon from Islet of Langerhans' alpha cells) forces release of glucose into the blood from cellular stores, primarily liver cell stores of glycogen. Untreated, Metabolic Syndrome can lead to morbidities such as essential hypertension, obesity, Type 2 diabetes, and cardiovascular disease (CVD). The chronic diabetic complications include cerebrovascular accidents (CVA or stroke), heart attack, blindness (from proliferative diabetic retinopathy), other vascular damage, nerve damage from diabetic neuropathy, or kidney failure from diabetic nephropathy.
This is not so; eighty years of insulin use has given no reason to believe it could be in any respect a performance enhancer for non diabetics.


In December 1921, Macleod invited the biochemist James Collip to help with this task, and, within a month, he felt ready to test.On January 11, 1922, Leonard Thompson, a fourteen-year-old diabetic, was given the first injection of insulin. She had been awarded a Nobel Prize in Chemistry in 1964 for the development of crystallography.
Release of insulin is strongly inhibited by the stress hormone norepinephrine (noradrenaline), which leads to increased blood glucose levels during stress.
Endogenous causes of insulin excess (such as an insulinoma) are very rare, and the overwhelming majority of hypoglycemia cases are caused by human action (e.g. Polycystic ovary syndrome – a complex syndrome in women in the reproductive years where there is anovulation and androgen excess commonly displayed as hirsutism. Some who cannot achieve adequate glucose control by conventional injection (or sometimes jet injection) are able to do so with the appropriate pump.An insulin pump is a reasonable solution for some. Glucose from some foods is absorbed more (or less) rapidly than the same amount of glucose in other foods. These studies have demonstrated beyond doubt that, if it is possible for a patient, so-called intensive insulinotherapy is superior to conventional insulinotherapy. Improperly treated diabetics are, to be sure, more prone than others to exhaustion and tiredness, and in some cases, proper administration of insulin can relieve such symptoms. Before this demonstration, the link between the pancreas and diabetes was clear, but not the specific role of the islets.
However, the extract was so impure that he suffered a severe allergic reaction, and further injections were canceled. Rosalyn Sussman Yalow received the 1977 Nobel Prize in Medicine for the development of the radioimmunoassay for insulin. One to three million islets of Langerhans (pancreatic islets) form the endocrine part of the pancreas, which is primarily an exocrine gland. However there are limitations - cost, the potential for hypoglycemic episodes, catheter problems, and, so far, no approvable means of controlling insulin delivery in the field based on current blood glucose levels. And, fats and proteins both cause delays in absorption of glucose from carbohydrate eaten at the same time. However, close control of blood glucose levels (as in intensive insulinotherapy) does require care and considerable effort, for hypoglycemia is dangerous and can be fatal.A good measure of long term diabetic control (over approximately 90 days in most people) is the serum level of glycosylated hemoglobin ( HbA1c). In October 1920, Frederick Banting was reading one of Minkowski's papers and concluded that it is the very digestive secretions that Minkowski had originally studied that were breaking down the secretion, thereby making it impossible to extract successfully. Over the next 12 days, Collip worked day and night to improve the extract, and a second dose injected on the 23rd.
If too much insulin is delivered, or the patient eats less than normal, there will be hypoglycemia. A shorter term integrated measure (over two weeks or so) is the so-called fructosamine level, which is a measure of similarly glyclosylated proteins (chiefly albumin) with a shorter half life in the blood. On top of this, non-prescribed insulin is a banned drug at the Olympics and other global competitions.
This was completely successful, not only in not having obvious side-effects, but in completely eliminating the symptoms of diabetes.
The former are important because of their central role in movement, breathing, circulation, etc, and the latter because they accumulate excess food energy against future needs. Non-diabetics' beta cells routinely and automatically manage this by continual glucose level monitoring and insulin release. However, Banting and Best never worked well with Collip, regarding him as something of an interloper, and Collip left soon after.Over the spring of 1922, Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the extract remained impure. These modifications of proinsulin remove the centre portion of the molecule, or C-peptide, from the C- and N- terminal ends of the proinsulin. All such decisions by a diabetic must be based on experience and training (ie, at the direction of a physician or PA, or in some places a specialist diabetic educator) and, further, specifically based on the individual experience of the patient. However, they had been approached by Eli Lilly and Company with an offer of help shortly after their first publications in 1921, and they took Lilly up on the offer in April.
The remaining polypeptides (51 amino acids in total), the B- and A- chains, are bound together by disulfide bonds. It is not straightforward and should never be done by habit or routine, but with care can be done quite successfully in practice.For example, some diabetics require more insulin after drinking skim milk than they do after taking an equivalent amount of fat, protein, carbohydrate, and fluid in some other form.
In November, Lilly made a major breakthrough, and were able to produce large quantities of pure insulin. Their particular reaction to skimmed milk is different from other diabetics', but the same amount of whole milk is likely to cause a still different reaction even in that person.
Nevertheless, he supplied Banting with a lab at the University, an assistant, medical student Charles Best, and ten dogs, while he left on vacation during the summer of 1921. Their method was tying a ligature (string) around the pancreatic duct, and, when examined several weeks later, the pancreatic digestive cells had died and been absorbed by the immune system, leaving thousands of islets. However, some diabetics are able to keep their glucose in reasonable control only on a pump.Researchers have produced a watch-like device that tests for blood glucose levels through the skin and administers corrective doses of insulin through pores in the skin. It is a continual balancing act for all diabetics, especially for those taking insulin.Insulin dependent diabetics require a base level of insulin (Basal Insulin), as well as extra short acting insulin to cope with meals (Bolus Insulin). Humulin was the first medication produced using modern genetic engineering techniques, in which actual human DNA is inserted into a host cell (E. Maintaining the basal rate and the bolus rate is a continuous balancing act that all insulin diabetics have to manage each day. This is normally achieved through regular blood tests, although there is work being undertaken on continuous blood sugar testing equipment.It is important to notice that diabetics generally need more insulin than the usual -- not less -- during physical stress like infections or surgeries. The host cells are then allowed to grow and reproduce normally, and due to the inserted human DNA, they produce actual human insulin.
Transplantation of an entire pancreas (as an individual organ) is difficult, and is not common. Additionally, some researchers have explored the possibility of transplanting genetically engineered non-beta cells to secrete insulin. When patients were switched from injected to inhaled insulin, no significant difference was found in HBA1c levels over three months.
Patients showed no significant weight gain or pulmonary function over the length of the trial, when compared to the baseline. Several clinical studies reported greater patient satisfaction compared with subcutaneous insulin in both type 1 and type 2 diabetes.An additional method of administration of insulin to diabetics is pulsatile insulin. In this method insulin is pulsed into the patient, mimicking the physiological secretions of insulin by the pancreas.



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