Decreased muscle insulin receptor kinase correlates with insulin
resistance in normoglycemic pima indians.
Youngren, Jack F., Ira D. Goldfine, and Richard E. Pratley.
Department of Medicine, Division of Diabetes and Endocrine
Research, Mount Zion Medical Center, University of California San
Francisco, San Francisco, California 94143-1616, Clinical Diabetes
and Nutrition Section, National Institute of Diabetes and Digestive
and Kidney Disease, National Institutes of Health, Phoenix, Arizona
85016
APStracts 4:0094E, 1997.
Defects in insulin receptor tyrosine kinase activity are present in
insulin resistant NIDDM patients and certain non-diabetic
individuals, both lean and obese. However, the relationship between
insulin receptor function, insulin action and obesity is unclear. To
address this issue, we have employed a new and highly sensitive ELISA
to measure in vitro insulin-stimulated autophosphorylation of
immunocaptured muscle insulin receptors in a group of 25
normoglycemic Pima Indians. Insulin action, determined during 2-step
euglycemic insulin clamps, varied widely in these subjects. Maximal
insulin stimulation of insulin receptor autophosphorylation strongly
correlated with both low (Mlow) and high dose (Mhigh) insulin
-stimulated glucose disposal (r = 0.62 and 0.51, P < 0.002 and
0.011, respectively). Insulin receptor autophosphorylation was
inversely related to % body fat (r = -0.52, P < 0.009). After
controlling for % body fat, receptor autophosphorylation remained
correlated with Mlow (partial r = 0.49, P < 0.025). These data
suggest, therefore, that defects in insulin receptor function are
major contributors to insulin resistance in both lean and obese
normoglycemic Pima Indians.
Received 18 December 1996; accepted in final form 26 March 1997.
APS Manuscript Number E619-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 13 May 1997