DECREASED MUSCLE INSULIN-RECEPTOR KINASE CORRELATES WITH INSULIN-RESISTANCE IN NORMOGLYCEMIC PIMA-INDIANS

Defects in insulin receptor tyrosine kinase activity are present in in sulin-resistant non-insulin-dependent diabetes mellitus patients and c ertain nondiabetic individuals. both lean and obese. However, the rela tionship between insulin receptor function. insulin action, and obesit y is unclear. To address this issue, we have employed a new and highly sensitive enzyme-linked immunosorbent assay to measure in vitro insul in-stimulated autophosphorylation of immunocaptured muscle insulin rec eptors in a group of 25 normoglycemic Pima Indians. Insulin action, de termined during two-step euglycemic insulin clamps, varied widely in t hese subjects. Maximal in vitro insulin stimulation of insulin recepto r autophosphorylation strongly correlated with both low (M-low)- and h igh (M-high)-dose insulin-stimulated glucose disposal (r = 0.62 and 0. 51, P < 0.002 and 0.011, respectively). Insulin receptor autophosphory lation was inversely related to percent body fat (r = -0.52, P < 0.009 ). After control for percent body fat, receptor autophosphorylation re mained correlated with M-low (partial r = 0.49, P < 0.025). These data therefore suggest that defects in insulin receptor function are major contributors to insulin resistance in both lean and obese normoglycem ic Pima Indians.