Complementary measures for promoting insulin sensitivity in skeletal muscle.
Insulin resistance of skeletal muscle is fundamental to both syndrome X and its frequent sequel, type II diabetes. In these disorders, excessive exposure of muscle to free fatty acids (FFAs) and their metabolic derivatives appears to play a prominent role in the induction of insulin resistance. Recent evidence suggests that activation of novel isoforms of protein kinase C (PKC) by diacylglycerol may mediate at least part of the adverse impact of FFAs on muscle insulin sensitivity. Vitamin E and fish oil omega-3s, by promoting the activity of diacylglycerol kinase and inhibiting that of phosphatidate phosphohydrolase, should reduce diacylglycerol levels, thus accounting for their documented favorable impact on insulin sensitivity. Thiazolidinediones such as troglitazone, on the other hand, appear to intervene in the signaling pathway whereby PKC down-regulates insulin function. The insulin-sensitizing activity of chromium picolinate may be attributable, at least in part, to increased expression of insulin receptors. In combination with lifestyle modifications which reduce FFA exposure--weight loss, very-low-fat eating, excessive training--these measures can be expected to work in a complementary way to promote increased numbers of insulin receptors that are more functionally competent. As these measures appear to be safe and well-tolerated, they may have utility for the prevention of diabetes as well as its therapy. When they do not prove sufficient to achieve optimal glycemic control, excessive hepatic glucose output and impaired cell response to glucose can be addressed with metformin and sulfonylureas, respectively. The prospects for a rational medical management of type II diabetes, obviating the need for injectible insulin, have never been brighter.
McCarty
M F
MF
Nutrition 21, San Diego, CA 92109, USA.
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002839:Chromans / Q000494:pharmacology; D002857:Chromium / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005395:Fish Oils / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D000077288:Troglitazone; D014639:Vanadium / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D002839:Chromans; D005230:Fatty Acids, Nonesterified; D005395:Fish Oils; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D014639:Vanadium; D002857:Chromium; D014810:Vitamin E; D011972:Receptor, Insulin; D011493:Protein Kinase C; D000077288:Troglitazone