Insulin resistance and type

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... 

For cardiovascular risk detecting and correcting factors like hypertension, obesity, insulin resistance, and type 2 diabetes or abnormal lipid profile, according to preestablished guidelines, can dramatically diminish the number of events. 

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. 

A.R. Saltiel and J.M. Olefsky, Thiazoli-dinediones in the treatment of insulin resistance and type II diabetes. Diabetes, 1996, 45, 1661-1669. 

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. 

Factors leading to characteristic dyslipidaemia are complex and not fully understood. Insulin resistance is associated with the failure of normal suppression of hormone-sensitive lipase in adipose tissue and increased lipolysis leading to increased flux of non-esterified fatty acids (NEFAs) to the liver this is partly responsible for increased hepatic output of very low-density lipoprotein (VLDL) [6]. Central obesity is common in insulin resistance and type 2 diabetes and visceral fat is increasingly recognised as an important paracrine and endocrine organ [7]. Adiponectin, an important adipose-specific adipokine, is reduced in insulin resistance and type 2 diabetes [8]. This would favour increased lipolysis as the action of a further important cytokine, TNF-alpha in stimulating lipolysis is unopposed. 

Birkenfeld, AL Shulman, Gl. Nonalcoholie Fatty Liver Disease, Hepatic Insulin Resistance, and Type 2 Diabetes. Hepatol, 2014 59(2) 713-23. 

Obesity is linked to major adverse health outcomes such as insulin resistance and type 2 diabetes. With obesity, adipose tissue mass expands and adipxxyte (fat cell) size increases. As previously discussed, canonical Wnt signaling pathway is essential for adipwgenesis and type 2 diabetes. Thus, canonical Wnt signaling plays an important role in the genesis of obesity. 

Sheng, T. and Yang, K., 2008. Adiponectin and its association with insulin resistance and type 2 diabetes. Journal of Genetics and Genomics 35(6), 321-326. 

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