Skeletal Muscle Insulin Resistance in Endocrine Disease

Abstract

We summarize the existing literature data concerning the involvement of skeletal muscle (SM) in whole body glucose homeostasis and the contribution of SM insulin resistance (IR) to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS), adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism.

Oligomeric Cocoa Procyanidins Possess Enhanced Bioactivity Compared to Monomeric and Polymeric Cocoa Procyanidins for Preventing the Development of Obesity, Insulin Resistance, and Impaired Glucose Tolerance during High-Fat Feeding

“…Insulin resistance occurs in skeletal muscle when a greater amount of insulin is required to stimulate the uptake of a given amount of glucose from the blood. In other words, when the cell becomes less responsive to insulin resulting in less glucose uptake 65,72 . This event leads to a greater amount of insulin secretion required for a given amount of glucose to be transported into the cell.…”

“…Overtime, this necessary increase in demand for the production of insulin causes the beta cells to have impaired insulin secretion functioning. interfere with insulin signaling may decrease insulin sensitivity in skeletal muscle 65,72,73 .…”

“…Tumor-necrosis factor-α (TNF-α), adiponectin, and leptin are the main adipokines associated with insulin resistance 72 . The adverse effects of the well-known cytokine TNF-α have been extensively studied and will be described in detail later in this review.…”

“…The adverse effects of the well-known cytokine TNF-α have been extensively studied and will be described in detail later in this review. Expression of the adipocyte-specific protein adiponectin, helps to modulate FFA catabolism via stimulation of various nuclear receptors thus contributing to lower levels of circulating FFA and glucose 72,74 .…”

“…Leptin is a hormone expressed mainly by adipose tissue that is linked to hypothalamus brain function that signals the feeling of satiety in addition to increasing insulin sensitivity 72,73 .…”