Type 2 Diabetes Mellitus is a chronic and systemic metabolic disorder distinguished by high blood glucose (hyperglycemia), insulin resistance, and insulin deficiency. The individual with Type 2 Diabetes typically goes undiagnosed for years because the onset is gradual and signs of hyperglycemia is not noticed. The long-term presence of type 2 diabetes impacts the large and small blood vessels and nerves throughout the body. The insulin signaling pathway refers to the complex biological process of insulin reacting with target cells such as muscle, fat, or liver cells and the resulting intracellular effects that result, leading to various functional effects observed at the multicellular level. Insulin works by binding its specific receptor on cell surfaces throughout the body, such as on liver, muscle or adipose cells.[5] The insulin receptor is a tyrosine kinase protein that undergoes autophosphorylation of its tyrosine residues that located on its cytoplasmic face once activated by insulin.
In total, the activation of the PI3K subpathway mediates several insulin-induced responses including GLUT4 activation, glycogen synthesis by inhibiting CSK-3 phosphorylation, and lipogenesis by up-regulation of fatty-acid synthase gene expression. MAPK is other main subpathway that is activated after IRS-1 and 2 phosphorylation that begins with small adaptor proteins Grb2 and SHP2 that lead to further substrate activation downstream. Insulin-mediated Glucose transport is primarily accounted for through the translocation of glucose transporters to the plasma membrane, most of which is GLUT4 within muscle and adipose cells. Most of glucose that enters human muscle in response to insulin is desposited as Glycogen (see Carbohydrate Storage: Glycogen for more information).
The biochemical process of glycolysis reverses many of the steps of Glycogenesis with different enzymes[64].
The Immune System of the human body is comprised of two different systems, the aquired immune system and innate immune system.
The innate immune system is the body’s first-line of defense against invaders including infections and physical or chemical injury. Research has shown that circulating concentrations of acute-phase reactants is increased in type 2 diabetic patients when compared to nondiabetic subjects. The Insulin Resistance Atherosclerosis Study (IRAS)[37] investigated the relationships insulin resistance, cardiovascular risk factors, and cardiovascular disease in a multiethnic population across varying statuses of glucose tolerance. Research indicates that increased ROS levels are associated with altered mitochondrial morphology in both myotubes cultured in high glucose conditions and in diet-induced diabetic mice.[16] In addition, increased oxidative stress in mitochondria may contribute to increased lipid peroxidation and damage to cell membranes and DNA. Apoptosis is a genetically directed process of cell self-destruction marked by the fragmentation of nuclear DNA.[45] It is a form of cell death during which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area.
Evidence suggests that the release of cytochrome c from the mitochondria results from direct action of ROS on cardiolipin, a mitochondrial phospholipid which is located in the inner mitochondrial membrane.[17][52][53] During the early phase of apoptosis, mitochondrial ROS production is stimulated and cardiolipin is oxidized (loses electrons). Although HbA1c is directly related to blood glucose levels, it is important to realize that blood glucose and HbA1c are not the same. A portion of the metabolic stress seen in Type 2 Diabetes may originate from myocellular fat storage. A four month study investigating the relationship between insulin sensitivity (IS) and IMCL content in Zucker diabetic fatty rats (ZDF) confirmed the relationship between IS and IMCL content seen in humans.
AMPK is a protein kinase, that combines signals to monitor and balance both systemic and cellular energy.
At times of high energy demand the ? subunit rapidly responds to changes in the AMP to ATP ratio to maintain energy balance. AMPK is activated by physical activity in such a way that increased intensity results in increased activation.
Reduction of AMPK activity promotes the development of insulin resistance and glucose intolerance, disturbs muscle energy balance during exercise, and decreases mitochondrial biogenesis (mitochondria’s ability to make ATP).[33] In insulin-resistant rodents, increased AMPK activity has been linked with improved blood glucose homeostasis, lipid profile and blood pressure.
In 2013, over 382 million people around the world had diabetes, and 90% of them had type 2 diabetes. Further reading: You can also read my previous article about 6 reasons you are tired all the time, in which health issues are one of them. Further reading: find here more health warnings your eyes may be sending and how to protect your eyes.
Further reading: Read my article about the top 15 causes of headaches and how to get rid of them naturally.
Further reading: read my precious articles about top signs that you have candida infection and what to do about it, and how to treat vaginal yeast infection naturally. If you are experiencing some of these symptoms, see your doctor so you can have a blood test and establish if you are indeed suffering from type 2 diabetes. Remember that type 2 diabetes is, to some degree, a preventable disease, and that the complications can be avoided with the right approach to life and health.
Being overweight – People with belly fat (visceral obesity) are especially at risk (find how to lose stubborn belly fat for good without counting calories in my ultimate e-book guide Blast Your Belly Fat).
Eating an unhealthy diet rich in red meat, unhealthy fats, sugars and processed food – One can of sugary soda a day increases your risk of diabetes by 22% (read my article about what happens to your body when you drink soda).


Generally speaking, you will do a lot if you try to eat healthy, exercise moderately, keep your stress levels under control and avoid bad habits. REALLY good list of symptoms that is all compiled in one place…even ones I had, but was never associated with the developing problem by doctors.
This website is designed for educational and informational purposes only, and the content herein should not be mistaken for professional health advice. Individuals commonly experience visual blurring, neuropathic complications, infections, fatigue and significant blood lipid abnormalities.[2][12] Type 2 Diabetes is typically diagnosed when the patient is receiving medical care for another problem. Chronic hyperglycemia can lead to macrovascular disease, which affects the arteries supplying the heart, brain, and lower extremities.[2] Type 2 diabetes is also associated with the development of microvascular pathologies in the retina, renal glomerulus, and peripheral nerves. Through PKB’s isoforms ?, ?, and ?, it plays role in mediating glycogen synthase kinase-3, metabolic actions of insulin, and Glut4 translocation.[8][66] It is debated whether PKB plays a significant role in insulin resistance with diabetes.
Mounting evidence has shown that PI3k and PKB activation participate in the stimulation of p70 S6k.
Insulin increases the transporters’ cycle to and from the cell surface by promoting exocytosis and inhibiting endocytosis. Insulin causes stable Glycogen Synthase (GS) activation by causing dephosphorylation at multiple sites within the enzyme. Through these three subpathways, the insulin signaling pathway promotes GS and glycogen synthesis. The aquired immune system is your immunity your body build up from being exposed to foreign invaders, and the innate immune system is the body's natural unspecific defense against new foreign invaders that the body has not built up immunity against. Participants demonstrated normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes mellitus.[37] Measures of insulin sensitivity and insulin secretion were obtained from all participants during two 4-hour visits, occurring approximately one week apart. Increased levels of ROS are a likely cause in a variety of pathophysiological conditions, including type 2 diabetes.[16] Oxidative stress to the mitochondria can come from many sources.
The amount of hemoglobin that forms HbA1c depends on the amount of glucose that hemoglobin is exposed to over time.[22],[23] For example, hemoglobin exposed to high levels of glucose for long periods of time results in greater amounts of glycation. The Diabetes Control Card is a quick reference for patients diagnosed with diabetes to assess glucose control. In muscle tissue, lipids are stored as either extramyocellular lipids (EMCL) or intramyocellular lipids (IMCL). An obese Zucker diabetic fatty rat has significantly higher IMCL concentrations than its lean counterpart. AMPK phosphorylates TBC1D1 which increases activity of GLUT4, resulting in increased glucose uptake. Frequent urination (polyuria): If you notice that you have to urinate more often, and you wake up during the night (sometimes several times) to empty your bladder, this could be a warning sign.
Increased hunger (polyphagia): Due to extreme highs and lows in blood sugar levels, the body develops a sudden urge to eat. Dry mouth: You experience a lack of moisture in the mouth, which can be both unpleasant and dangerous. Unexplained weight loss or weight gain: As insulin can’t get glucose into the cells, the body reacts as if it would be starving and starts using proteins from the muscles. Fatigue: Excessive tiredness can develop when body constantly compensates for the lack of glucose in the cells. Headaches – A headache can develop due to elevated blood sugar levels and is considered an early sign of hyperglycemia (high blood glucose).
Infections, cuts and bruises that do not heal: This classic sign of diabetes is a consequence of blood vessel damage.
Yeast infections: Since bacteria and fungi thrive in a sugary environment, infections can become more common. Skin changes: Velvety dark skin, known as achantosis nigricans, can appear on the neck, groin and armpit.
Sexual dysfunction: Diabetes also damages blood vessels and nerves in the sex organs, which can lead to different sexual problems. As we get older, the risk of diabetes increases, so it’s even more important to promote a healthy lifestyle and stay active. If you have a medical problem you should seek advice from a doctor and other health care professional. If you registered this domain name as a direct customer of Melbourne IT, please click here to renew your domain name. Raf phosphorylates MEK, a dual-specificity kinase of tyrosine and threonine that activates mitogen-activated protein kinase (MAPK). It has been shown that tyrosine kinase activity and IRS-1-protein phosphorylation are two essential processes in normal glucose transport.


PKB has also been shown to directly inhibit GSK-3, a well-known inhibitor of GS, thereby promoting GS. Ezymes responsible for Glycogenolysis 1 through 3 respectively: Glycogen phosphorylase, Phosphoglutomutase, Phosphoglutomutase, and Glucose-6 Phosphotase. ROS are produced in larger amounts by islet cells from patients with type 2 diabetes than by those from non-diabetic patients.[17] Although some ROS are produced in the peroxisomes, the major source of ROS production in cells is the mitochondria. This is directly related to continuous breakdown and replacement of erythrocytes in the body. EMCL is metabolically static, but IMCL stores are built up, mobilized, and used within hours. Production of insulin – a pancreatic hormone that usually deals with balancing blood sugar levels – is either reduced or the cells don’t respond to it properly. As you lose more fluids, the body will try to replenish them, hence the constant need to drink. Dry mouth can become a breeding ground for bacteria and cause different oral and dental problems. Rapid, unexplained weight loss (10 to 20 pounds over a couple of months) is not healthy and requires further investigation. Excessive amounts of sugar harm the veins and arteries, so they become less able to transport blood to where it is needed to repair and heal the damage.
The most frequent ones are yeast infections, such as candida, especially vaginal candida infections in women.
You can also observe other unusual skin changes and itchiness, especially around the vaginal or groin area. If you registered this domain name via a reseller of Melbourne IT, please contact the reseller to renew this domain.
The MAPK pathway is well known within the insulin signaling cascade, but is not very sensitive to insulin or involved in most of the hormone’s important metabolic responses.[8] The MAPK subpathway has some evidence showing it functions to exert feedback regulation on the PI3k subpathway and is involved in the process of insulin resistance. The PI3k subpathway functions to mediate glut4 activation, glycogen synthesis, and lipogenesis.
Within these pathways, PI3k, PKB, and the atypical PKCs play an particularly key roles in the process of glucose uptake into cells. MAPK has been implicated in activating GS through phosphorylation of p90 Ribosomal S6 kinase 2 (p90 rsk2) and glycogen bound protein phosphatase-1 (PP1G) downstream. The later branch is implicated GS promotion by inhibition of the well-established inhibitor of GS, GSK-3. During times of high glucose uptake, increased amounts of glucose-6-phosphate (G6P) leads to an increase in glycogen synthesis. As diabetes is a serious condition that can cause dangerous complications – including cardiovascular and neurological damage – it is important to detect it as soon as possible. If sugar levels are not brought down, the nerve damage can become permanent and presents a serious complication of diabetes.
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In contrast, the downstream constituents of PKB such as p70 S6k have been shown to have no immediate effects on glucose uptake.
PP1G has many phosphorylation sites that insulin has been shown to augment, but its exact role in GS promotion is not fully understood.
With the right diet, exercise regimen and, if necessary, medications, diabetes can be kept under control, and the person can continue to live a fulfilling life.
The MAPK subpathway may serve to regulate the PI3k subpathway and may be involved in insulin resistance, but more research is needed to prove this. Indirect activators (metformin, dinitrophenol (DNP), and rotenone) work by increasing AMP:ATP ratio, compound C works by inhibiting activation of AICAR. Find out about some of the early warning signs of diabetes, so you can act on it and protect your health. If you have been diagnosed as prediabetic, read my article about the 7 effective steps to prevent diabetes. However, if sugar levels stay high for a long period of time, this can cause permanent damage and can even lead to eyesight loss.



Normal blood sugar level hour after eating normal
What is normal random blood-glucose reading online


Comments

  1. 28.10.2014 at 20:57:20


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    Author: Seytan_Qiz
  2. 28.10.2014 at 16:39:53


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  3. 28.10.2014 at 14:41:33


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  4. 28.10.2014 at 11:21:32


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    Author: YuventuS
  5. 28.10.2014 at 10:53:13


    Run in families how well the individual is using insulin.

    Author: Bratka