Exercise is a potent stimulator of glucose transport in skeletal muscle that is independent of, and additive to, the effect of insulin. As this effect wears off after exercise it is replaced by an increase in sensitivity of muscle glucose transport to insulin that can last for days. Insulin resistance, resulting in impaired glucose tolerance or non-insulin dependent diabetes, is a major health problem in the U.S. that appears to be, in large part, an exercise deficiency disease. In this context, our long-term objective is to obtain a better understanding of the effects of exercise, and its interactions with insulin, on glucose transport in muscle, and to elucidate the mechanisms by which they are mediated.
One aim of this research is to examine the short-term effects of exercise and the long-term effects of exercise training or in situ contractile activity on the total glucose transporter content of skeletal muscle. The purpose of this phase of the research is to determine whether changes in total glucose transporter number play a role in mediating the effects of contractile activity on glucose transport. A second, related aim is to determine the role of glucose transporter translocation in mediating the action of muscle contractions alone, and in conjunction with insulin, on glucose transport. One purpose of this phase of the research is to evaluate the possibility that an increase in transporter intrinsic activity also plays a role. In these studies we will use a potent antiserum that is specific for the regulatable glucose transporter found in muscle and adipocytes.
A third aim i s to determine if protein kinase C (PKC) mediates a step in the exercise and/or insulin-mediated pathways for activating glucose transport in skeletal muscle. This phase of the research is, in part, a follow-up of preliminary studies showing that inhibitors of PKC block the stimulation of glucose transport.
A fourth aim i s to test the hypothesis that the increase in cytoplasmic Ca2+ during stimulation of muscle contractions activates a separate series of events, independent of contraction, that result in an increase in glucose transport activity.
| Han, Dong-Ho; Kim, Sang Hyun; Higashida, Kazuhiko et al. (2012) Ginsenoside Re rapidly reverses insulin resistance in muscles of high-fat diet fed rats. Metabolism 61:1615-21 |
| Han, Dong-Ho; Hancock, Chad R; Jung, Su Ryun et al. (2011) Deficiency of the mitochondrial electron transport chain in muscle does not cause insulin resistance. PLoS One 6:e19739 |
| Han, Dong-Ho; Hancock, Chad; Jung, Su-Ryun et al. (2009) Is ""fat-induced"" muscle insulin resistance rapidly reversible? Am J Physiol Endocrinol Metab 297:E236-41 |
| Hancock, Chad R; Han, Dong-Ho; Chen, May et al. (2008) High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci U S A 105:7815-20 |
| Geiger, Paige C; Hancock, Chad; Wright, David C et al. (2007) IL-6 increases muscle insulin sensitivity only at superphysiological levels. Am J Physiol Endocrinol Metab 292:E1842-6 |
| Terada, Shin; Wicke, Scott; Holloszy, John O et al. (2006) PPARdelta activator GW-501516 has no acute effect on glucose transport in skeletal muscle. Am J Physiol Endocrinol Metab 290:E607-11 |
| Geiger, Paige C; Han, Dong Ho; Wright, David C et al. (2006) How muscle insulin sensitivity is regulated: testing of a hypothesis. Am J Physiol Endocrinol Metab 291:E1258-63 |
| Otani, Kenichi; Polonsky, Kenneth S; Holloszy, John O et al. (2006) Inhibition of calpain results in impaired contraction-stimulated GLUT4 translocation in skeletal muscle. Am J Physiol Endocrinol Metab 291:E544-8 |
| Wright, David C; Geiger, Paige C; Han, Dong-Ho et al. (2006) Are tyrosine kinases involved in mediating contraction-stimulated muscle glucose transport? Am J Physiol Endocrinol Metab 290:E123-E128 |
| Geiger, Paige C; Wright, David C; Han, Dong-Ho et al. (2005) Activation of p38 MAP kinase enhances sensitivity of muscle glucose transport to insulin. Am J Physiol Endocrinol Metab 288:E782-8 |
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