Insulin and obesity in the zucker genetically obese rat “Fatty”

Abstract

Insulin status and functional activity have been studied during the life of the Zucker “fatty” rat (an obese mutant). Serum immunoreactive insulin (IRI) is normal at 2 weeks when fattening is beginning, rises to a peak of 400 μ-U/ml at 15 weeks while fattening proceeds rapidly, then drops to near 200 μU/ml in older rats. This was observed with two normal diets and a high protein diet. When fattening is reversed by fasting adult “fatties,” IRI remains abnormally high until body lipid has returned to normal (79 days). Blood sugar, basally and after a glucose load, is normal in young and old “fatties,” and is barely above normal at peak IRI. Sugar falls to below 50 mg/100 ml with prolonged fasting. Amino nitrogen tends to be slightly low, free fatty acids (FFA) are very high, in “fatties.” There is a developing resistance of diaphragm to glucose uptake in vivo, both basally and after injected insulin. The role of elevated FFA in this resistance to glucose uptake by muscle is not known. Basal glucose uptake in vivo per g of adipose tissue remains approximately normal in “fatties” the insulin stimulated response is excessive in young rats, subnormal in older “fatties”. However, basal uptake per fat cell is probably well above normal even in older “fatties”, and is comparable to that of the normal fat cell stimulated with insulin. There is no evidence of biological ineffectiveness of insulin in controlling sugar. Peripheral resistance to glucose uptake (muscle) is countered by peripheral receptiveness to glucose (adipose tissue). Degree of obesity, and relative fat cell size, are correlated with serum IRI elevation, suggesting a causal relation, with some indication that obesity precedes hyperinsulinemia. Whether, and how, obesity could cause increased output of insulin is not known. © 1972 by The Endocrine Society.