QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Adamo, M. Articles by LeRoith, D. Search for Related Content PubMed PubMed Citation Articles by Adamo, M. Articles by LeRoith, D.

Liver Insulin Receptor Tyrosine Kinase Activity in a Rat Model of Type II Diabetes Mellitus and Obesity

Martin Adamo^*, Joshua Shemer^*, Meir Aridor^*, Jan Dixon^*, Nancy Carswell, Sam J. Bhathena, Otho E. Michaelis, IV and Derek LeRoith^*,1

^* Section on Molecular and Cellular Physiology, Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 Carbohydrate Nutrition Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, Maryland 20705

Spontaneous hypertensive-corpulent rats (SHR/N-corpulent), homozygous for the corpulent gene (cp/cp), are obese, hyperinsulinemic and exhibit abnormal glucose tolerance and thus represent a model for type II diabetes and obesity. In view of their overall insulin resistance, we examined liver insulin receptor binding and tyrosine kinase activity from corpulent rats and lean littermates fed purified diets containing 54% sucrose or starch for about 12 wk. Specific ¹²⁵I-insulin binding to crude liver membranes from female corpulent rats fed either starch or sucrose was reduced to approximately 50% of that seen in lean rats (14 vs. 7%). Affinity of insulin receptors was similar in all groups, suggesting that hyperinsulinemic corpulent rats possess fewer hepatic insulin receptors than do lean rats. Using similar numbers of wheat germ agglutinin-agarose (WGA)-purified insulin receptors with similar affinities for insulin, it was found that basal and insulin-stimulated phosphorylation of the synthetic tyrosine-specific kinase substrate poly(Glu, Tyr)4:1 was similar in lean and obese rats fed sucrose or starch. It is suggested that the contribution of the liver to the insulin resistance in obese SHR/N-cp rats probably lies distal to the insulin receptor tyrosine kinase.

KEY WORDS: • insulin resistance • insulin receptor tyrosine kinase • genetically obese rats • insulin receptor down regulation • rat model of type II diabetes mellitus

¹ To whom reprint requests and correspondence should be addressed.

Manuscript received 20 July 1988. Revision accepted 24 October 1988.