The extracellular matrix (ECM) is a highly dynamic compartment that undergoes remodeling as a result of injury and repair. Over the past decade, mounting evidence in humans and rodents suggest that ECM remodeling is associated with diet-induced insulin resistance in several metabolic tissues. Additionally, integrin receptors for the ECM have also been implicated in the regulation of insulin action. This review will address what is currently known about the ECM, integrins and insulin action in the muscle, liver and adipose tissue. Understanding how ECM remodeling and integrin signaling regulates insulin action may aid in the development of new therapeutic targets for the treatment of insulin resistance and type 2 diabetes.

In summary, 1000 mg x d(-1) Q versus P for 2 wk by untrained males was associated with a small but significant improvement in 12-min treadmill time trial performance and modest but insignificant increases in the relative copy number of mitochondrial DNA and messenger RNA levels of four genes related to mitochondrial biogenesis.

Protein hyperacetylation is associated with glucose intolerance and insulin resistance, suggesting that the enzymes regulating the acetylome play a role in this pathological process. Sirtuin 3 (SIRT3), the primary mitochondrial deacetylase, has been linked to energy homeostasis. Thus, it is hypothesized that the dysregulation of the mitochondrial acetylation state, via genetic deletion of SIRT3, will amplify the deleterious effects of a high-fat diet (HFD). Hyperinsulinemic-euglycemic clamp experiments show, for the first time, that mice lacking SIRT3 exhibit increased insulin resistance due to defects in skeletal muscle glucose uptake. Permeabilized muscle fibers from HFD-fed SIRT3 knockout (KO) mice showed that tricarboxylic acid cycle substrate–based respiration is decreased while fatty acid–based respiration is increased, reflecting a fuel switch from glucose to fatty acids. Consistent with reduced muscle glucose uptake, hexokinase II (HKII) binding to the mitochondria is decreased in muscle from HFD-fed SIRT3 KO mice, suggesting decreased HKII activity. These results show that the absence of SIRT3 in HFD-fed mice causes profound impairments in insulin-stimulated muscle glucose uptake, creating an increased reliance on fatty acids. Insulin action was not impaired in the lean SIRT3 KO mice. This suggests that SIRT3 protects against dietary insulin resistance by facilitating glucose disposal and mitochondrial function.

The accelerated metabolic demands of the working muscle cannot be met without a robust response from the liver. If not for the hepatic response, sustained exercise would be impossible. The liver stores, releases, and recycles potential energy. Exercise would result in hypoglycemia if it were not for the accelerated release of energy as glucose. The energetic demands on the liver are largely met by increased oxidation of fatty acids mobilized from adipose tissue. Adaptations immediately following exercise facilitate the replenishment of glycogen stores. Pancreatic glucagon and insulin responses orchestrate the hepatic response during and immediately following exercise. Like skeletal muscle and other physiological systems, liver adapts to repeated demands of exercise by increasing its capacity to produce energy by oxidizing fat. The ability of regular physical activity to increase fat oxidation is protective and can reverse fatty liver disease. Engaging in regular physical exercise has broad ranging positive health implications including those that improve the metabolic health of the liver.

Two-week supplementation with Q-EGCG was effective in augmenting GOBA andin countering inflammation after 3 d of heavy exertion in trained cyclists.