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.
The real story is that the number, size, and density of cholesterol particles in your blood (LDL-P and HDL-P) are far better predictors of heart disease risk.


The best way to measure your heart disease risk through LDL cholesterol is to measure the number of LDL particles in your blood, or LDL-P, which you never get checked unless you have a fancy test called a lipid nuclear magnetic resonance test – or NMR test for short.
You can look at particle size.  As a general rule (this is NOT always the case, however), the larger the LDL particles, for a given LDL-C, the fewer the particles (which is what we want).
Below is graph of my overall change in changes in HDL-C, LDL-C, and TG, along with the ratio of my TG to HDL-C, based on the “standard” cholesterol panel. As I stated above, a better marker of risk with respect to LDL is particle number, LDL-P – the fewer particles, the better; and you can estimate this by measuring particle size, or through concentration of ApoB. Unfortunately, I only started doing regular VAP testing about a year ago, over one year into my “experiment” of progressive carbohydrate restriction.  Hence, I can’t show my progress as longitudinally with VAP as I can with standard cholesterol testing.
Below is figure showing the change in my VAP panel over a seven month period, between January and July 2011. Keep in mind how my diet changed between January and July – I reduced carbohydrate intake from approximately 150 grams per day of “good” carbs to less than 50 grams per day.  I also increased, dramatically, my intake of fat, including saturated fats. Despite the amount of time I’ve expended on explaining all of these nuances of “cholesterol” numbers, I am not entirely convinced that I am healthier today because my cholesterol numbers are better.  I wonder if I’m healthier today because of something else, and that whatever else is making me healthier is also correcting my cholesterol problem? If I had to guess what is really making me healthier today, besides being less fat, I believe it is the combination of how sensitive I’ve become to insulin and how much less inflammation I have in my body, especially in and around my arteries.
As I mentioned above, findings #1, 2, and 4 are almost universal in folks who abandon carbohydrates, while finding #3 is somewhat variable.
Which of these is most important?  This is an obvious and important question, but one I don’t really know the answer to (nor does anyone else, for that matter).  If I had to guess, I believe observation #4 is the most important because insulin resistance is the underpinning of metabolic syndrome. People have said things to me like, “Well it’s great that you’ve reduced your risk of all diseases associated with metabolic syndrome, but wouldn’t it be funny if you got hit by a car tomorrow!”  All kidding aside, this misses the point.
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. Well, there are two: what can I actually measure that predicts my risk of heart disease, and how does diet affect these these things I can measure? Basically it’s a test to measure how much insulin a person needs to keep their glucose level constant, despite the addition of glucose.  The less insulin one requires, the more insulin sensitive one is.
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. 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.
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.
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.



Diabetes symptoms type 1 vs type 2
Blood glucose level chart hypoglycemia guideline
What is low blood sugar level for a diabetic
Range of diabetes on blood sugar level


Comments

  1. 15.12.2014 at 18:48:16


    Description of several T1D-associated autoantibodies provided.

    Author: O_R_K_H_A_N
  2. 15.12.2014 at 21:53:12


    Design and intensity definition thereby obviating hypoglycemia does not generally cleaned with.

    Author: QARA_VOLQA