AJP - Regulatory, Integrative and Comparative Physiology, Vol 266, Issue 3 921-R928, Copyright © 1994 by American Physiological Society
The VMH-dietary obese rat: a new model of non-insulin-dependent diabetes mellitus
K. V. Axen, X. Li, K. Fung and A. Sclafani
Department of Health and Nutrition Sciences, Brooklyn College of City University of New York 11210.
A model of non-insulin-dependent diabetes mellitus (NIDDM) has been
developed in adult rats by combining bilateral electrolytic lesions of the
ventromedial hypothalamus (VMH) and high fat-high sucrose diets.
VMH-dietary obese rats showed fasting hyperinsulinemia (> or = 540 pM)
and hypertriglyceridemia (> or = 180 mg/dl) generally within 3 wk on the
protocol. Fasting hyperglycemia (> or = 10 mM) was observed in the
majority of animals in seven consecutive experiments. Hyperglycemic animals
showed impaired glucose tolerance despite high prevailing insulin levels.
Pancreatic islets isolated from VMH-dietary obese rats showed a loss of
insulin secretory response to glucose by week 5, before the onset of
hyperglycemia. Islets from hyperglycemic rats no longer responded to an
increase in glucose concentration and failed to suppress insulin release
normally 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 secretory defects in the syndrome.
