THE VMH-DIETARY OBESE RAT - A NEW MODEL OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS

A model of non-insulin-dependent diabetes mellitus (NIDDM) has been de veloped in adult rats by combining bilateral electrolytic lesions of t he ventromedial hypothalamus (VMH) and high fat-high sucrose diets. VM H-dietary obese rats showed fasting hyperinsulinemia (greater than or equal to 540 pM) and hypertriglyceridemia(greater than or equal to 180 mg/dl) generally within 3 wk on the protocol. Pasting hyperglycemia ( greater than or equal to 10 mM) was observed in the majority of animal s in seven consecutive experiments. Hyperglycemic animals showed impai red glucose tolerance despite high prevailing insulin levels. Pancreat ic islets isolated from VMH-dietary obese rats showed a loss of insuli n secretory response to glucose by week 5, before the onset of hypergl ycemia. Islets from hyperglycemic rats no longer responded to an incre ase in glucose concentration and failed to suppress insulin release no rmally in response to 15 nM norepinephrine or to a decrease in glucose concentration. This model mimics the major characteristics of obesity -associated human NIDDM as well as several stages of its progression, rendering it useful for studying the etiology of the metabolic and sec retory defects in the syndrome.