Insulin Resistance and Hypertension: Glucose Intolerance, Hyperinsulinemia, and Elevated Free Fatty Acids in the Lean Spontaneously Hypertensive Rat

Abstract

Recent evidence suggests that insulin resistance may be a feature of essential hypertension in humans. However, there is some dispute over suitable animal models. To clarify these issues, we performed oral glucose tolerance tests in lean spontaneously hypertensive rats (SHR) as well as in age-matched normotensive rats from the parent Wistar-Kyoto (WKY) strain. In response to feeding, SHR were significantly hyperglycemic and hyperinsulinemic compared to WKY. In addition, free fatty acids were significantly higher throughout the oral glucose tolerance tests in SHR compared to WKY. Furthermore, this apparent insulin resistance occurred despite the fact that SHR were significantly leaner than age-matched WKY. When growth curves were compared for the two strains fed ad libitum, both SHR and WKY gained weight appropriately during the period of observation, although SHR were significantly lighter throughout. It is concluded that SHR express insulin resistance in terms of glucose and fatty acid metabolism, and therefore are a suitable model for insulin resistance and essential hypertension in non-obese humans. Further studies are needed to clarify the pathophysiologic defects leading to insulin resistance in these animals.