Chemically chaperoning the actions of insulin.
The role of inflammation as a mediator of insulin resistance in type 2 diabetes and obesity has been a major focus of studies over the past ten years. In mouse models of obesity and type 2 diabetes, the development of insulin resistance correlates with elevated levels of endoplasmic reticulum stress and induction of the unfolded protein response. Activation of N-terminal C-Jun kinase is known to be associated with unfolded protein response activation, and has been shown to participate in the inhibition of insulin action by stimulating serine phosphorylation of the insulin receptor substrate 1, an event that attenuates insulin signaling. 'Chemical chaperones' are small molecules that have been shown to attenuate unfolded protein response activation. The exciting new findings of Ozcan et al. indicate that chemical chaperones improve glucose tolerance and insulin action in a mouse model of type 2 diabetes. These findings offer a potential new target for therapeutic strategies designed to improve insulin action and glucose tolerance in diabetic individuals.
Hansen
Polly A
PA
E.A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1402 S. Grand Boulevard, St Louis, MO 63104, USA.
Waheed
Abdul
A
Corbett
John A
JA
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008954:Models, Biological; D009765:Obesity / Q000209:etiology; D015398:Signal Transduction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin