Insulin resistance in type 2 diabetes

Defects in glucose uptake into muscle cells are characteristic of insulin resistance in type 2 diabetes and the metabolic syndrome. This phenomenon is likely to be due to reduced activity of a transporter that operates by what mechanism ... 

Insulin resistance in type 2 diabetes contributes to reduced efficacy of both endogenous and exogenous insulin. When metformin and pioglitazone were compared in patients who had not taken previous drug therapy, they were equally efficacious in glycemic control, but parameters of insulin sensitivity increased much more with pioglitazone (83). 

Luo, J., Van Yperselle, M., Rizkalla, S., Rossi, F., Bomet, F.R.J., and Slama, G., Chronic consumption of short-chain fructoligosaccharides does not affect basal glucose production or insulin resistance in type 2 diabetics, J. Nutr., 130, 1572-1577, 2000. 

Peutzner,A., Kunt, T, Hohberg, C., Mondok, A., Pahler, S., Konrad, T, Lubben, G., Forst, T. (2004). Fasting intact proinsulin is a highly specific predictor of insulin resistance in type 2 diabetes. Diabetes Care 27, 682-687. 

SITE OF INSULIN RESISTANCE IN TYPE 2 DIABETES Liver... 

Muscle is the major site of glucose disposal in man, and approximately 80% of total body glucose uptake occurs in skeletal muscle. In response to a physiologic increase in plasma insulin concentration, muscle glucose uptake increases linearly, reaching a plateau value of 10 mg/kg per minute. In contrast, in lean type 2 diabetic subjects, the onset of insulin action is delayed for 40 minutes, and the ability of insulin to stimulate leg glucose uptake is reduced by 50%. Therefore the primary site of insulin resistance in type 2 diabetic subjects resides in muscle tissue. 

Kelley DE, Williams KV, Price JC, et al. Plasmafatty acids, adiposity and variance of skeletal muscle insulin resistance in type 2 diabetes mellitus. J Clin Endocrinol Metab 2001 86 5412-5419. 

Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance in type 2 diabetes. Endcr Rev. 2002 23 201-229. 

Gupta, A., R. Gupta, and B. Lai. 2001. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes melUtus A double blind placebo controlled study. /. Assoc. Physicians India 49 1057-1061. 

Hsu, C.H., Liao, Y.L., Lin, S.C., Hwang, K.C., and Chou, P. 2007. The mushroom Agaricus Blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes a randomized, double-blinded, and placebo-controlled clinical trial. Journal of alternative and complementary medicine (New York. N.Y.), 13(1), 97-102. 

Adachi, T. Inoue, M. Hara, H. Maehata, E. Suzuki, S. (2004). Relationship of plasma extracellular-superoxide dismutase level with insulin resistance in type 2 diabetic patients. / Endocrinol, Vol. 181, No. 3, pp. 413 17, ISSN 0022-0795. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

The role of IMCL in the pathogenesis of insulin resistance and type 2 diabetes... 

To gain further insight into the mechanisms involved in defective insulin-stimulated glucose uptake in skeletal muscle of insulin-resistant subjects, the possible role of IMCL in the pathogenesis of skeletal muscle insulin resistance and type 2 diabetes mellitus was explored by comparing insulin sensitivity (GIR) and IMCL content of insulin-resistant and insulin-sensitive offsprings of patients with type 2 diabetes. Twenty-six healthy subjects were included in the first study, 13 of them classified as insulin-sensitive and further 13 as insulin-resistant. Metabolic and anthropometric data are given in Table 4. 

Low LPL activity can also be found secondary to metabolic dysregulation, notably in insulin resistance and type 2 diabetes mellitus. In fact, diabetic hypertriglyceridemia is caused in part by decreased LPL secretion in response to reduced insulin action. Another preanalytical pitfall results from the high affinity of LPL for triglyceride-rich lipoproteins. When extremely hypertriglyceridemic plasma is prepared by cen-... 

Insulin resistance and type 2 diabetes Insulin resistance alone will not lead to type 2 diabetes. Rather, type 2 diabetes develops in insulin-resistant individuals who also show impaired p cell function. Insulin resistance and subsequent development of type 2 diabetes is commonly observed in the elderly, and in individuals who are obese, physically inactive, or in women who are pregnant. These patients are unable to sufficiently compensate for insulin resistance with increased insulin release. Figure 25.8 shows the time course for the develpment of hyperglycemia and the destruction of P cells. 

Vanadium compounds have also been shown to be effective in animal models of insulin resistance and type 2 diabetes. Oral administration of vanadium compounds lowered blood glucose levels to near normal in the ob/ob and db/db mouse and fa/fa rat [149-151], These rodent models are homozygous for the indicated gene and are characterized by obesity, hyperglycemia, and hyperinsulinemia [12]. The ob allele is the gene for leptin, whereas db and fa are the genes for the leptin receptor in the mouse and rat, respectively. Leptin is one of the cytokine hormones that are produced in fat cells and act on receptors in the central nervous system. Its effects involve inhibition of food intake and promotion of energy expenditure [99],... 

Treatment with either vanadium salts or organic complexes of vanadium have decreased plasma insulin levels and improved insulin sensitivity in animal models of both insulin resistance and type 2 diabetes. This work has recently been reviewed [13]. The Zucker Diabetic Fatty (ZDF) rat develops overt hyperglycemia in the presence of hyperinsulinemia followed by [3-cell depletion. This is a type 2 diabetic rat model developed from the Zucker Fatty (fa/fa) rat. In these animals, chronic treatment with vanadium reduced the elevated plasma glucose levels [152,153], The effect in the type 2 models of diabetes can take weeks to develop, whereas the effect in the type 1 models of diabetes are seen within 3 to 4 days. 

Epidemiological studies have identified a number of factors that contribute to the risk of developing cirrhosis. Regular (moderate) alcohol consumption, age older than 50 years, and male gender are examples that increase cirrhosis risk in chronic hepatitis C infection, and older age, obesity, insulin resistance or type 2 diabetes, hypertension and hyperlipidaemia in non-alcoholic steatohepatitis. 

The low molecular weight acid phosphatase has been implicated in the insulin resistance pathway producing effects that are independent from the high molecular weight protein tyrosine phosphatase (PTPIB) [37, 38]. This renders the low molecular weight protein tyrosine acid phosphatase an interesting target for the treatment of insulin resistance and type 2 diabetes. 

Lake, S., A. Krook, and J. R. Zierath. 2003. Analysis of insulin signaling pathways through comparative genomics. Mapping mechanisms for insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus. Exp Clin Endocrinol Diabetes 111 191-7. 

---