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Effect of Dietary Carbohydrates on Glucagon and Insulin Receptors in Genetically Obese Female Zucker Rats

Carbohydrate Nutrition Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD 20705 ^* Diabetes Research Laboratory, Veterans Administration Medical Center, Washington, DC 20422

Obese Zucker rats are hyperlipemic and mildly hyperglycemic. Because insulin and glucagon are involved in lipid and carbohydrate metabolism and they act via their receptors, we investigated the role of insulin and glucagon receptors in obese and lean female Zucker rats. Because dietary sucrose is more lipogenic than starch, we also studied the effect of dietary carbohydrates on the receptors. Significant phenotypic effect (obese > lean) was observed on plasma levels of glucose, triglyceride and insulin. Binding of insulin and glucagon to liver plasma membranes was significantly lower in obese rats than in lean rats. Lower insulin binding was due to a lower number of receptors as well as a lower affinity, whereas the lower glucagon binding was due only to a lower receptor number. Insulin binding in lean rats but not in obese rats was lower in sucrose-fed than in starch-fed rats. Diet had no effect on glucagon binding. We propose that in obese Zucker rats, in addition to hyperinsulinemia, impaired glucagon activity as manifested by decreased glucagon binding to target tissues may be an important contributor to the hyperlipemia and obesity.

KEY WORDS: • insulin receptor • glucagon receptor • liver plasma membranes • obesity • Zucker rat • dietary sucrose

¹ To whom reprint requests should be addressed.

Manuscript received 16 September 1986. Revision accepted 3 March 1987.