Insulin resistance and improvements in signal transduction
ABSTRACT Type 2 diabetes and obesity are common metabolic disorders characterized by resistance to the actions of insulin to stimulate skeletal muscle glucose disposal. Insulin-resistant muscle has defects at several steps of the insulin-signaling pathway, including decreases in insulin-stimulated insulin receptor and insulin receptor substrate-1 tyrosine phosphorylation, and phosphatidylinositol 3-kinase (PI 3-kinase) activation. One approach to increase muscle glucose disposal is to reverse/improve these insulin-signaling defects. Weight loss and thiazolidinediones (TZDs) improve glucose disposal, in part, by increasing insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation and PI 3-kinase activity. In contrast, physical training and metformin improve whole-body glucose disposal but have minimal effects on proximal insulin-signaling steps. A novel approach to reverse insulin resistance involves inhibition of the stress-activated protein kinase Jun N-terminal kinase (JNK) and the protein tyrosine phosphatases (PTPs). A different strategy to increase muscle glucose disposal is by stimulating insulin-independent glucose transport. AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge and becomes activated in situations of energy consumption, such as muscle contraction. Several studies have shown that pharmacologic activation of AMPK increases glucose transport in muscle, independent of the actions of insulin. AMPK activation is also involved in the mechanism of action of metformin and adiponectin. Moreover, in the hypothalamus, AMPK regulates appetite and body weight. The effect of AMPK to stimulate muscle glucose disposal and to control appetite makes it an important pharmacologic target for the treatment of type 2 diabetes and obesity.
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ABSTRACT: This study investigated the effects of endurance exercise and ginsenoside on AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K) protein expression and glucose uptake in the skeletal muscle of rats. A total of 32 rats were randomly divided into four groups: CON (Control group, n=8), Ex (Exercise group; 25 m/min for 1 h, 6 days/week, 2 weeks, n=8), (Ginsenoside group; n=8), and (+Exercise group, n=8). The and groups were incubated in ginsenoside (KRBP buffer, ) for 60 min after a 2-week experimental treatment. After 2 weeks, the expression of phosphorylated , total , the p85 subunit of PI3K, pIRS-1 , and pAkt were determined in the soleus muscle. Muscle glucose uptake was measured using 2-deoxy-D- glucose in epitroclearis muscle. Muscle glucose uptake was significantly higher in the three experimental groups (Ex, , ) compared to the CON group (PJournal of the Korean Society of Food Science and Nutrition 08/2013; 42(8). DOI:10.3746/jkfn.2013.42.8.1197