Enhanced Glucose Tolerance in Spontaneously Hypertensive Rats: Pancreatic β-Cell Hyperfunction With Normal Insulin Sensitivity

We used intravenous glucose tolerance tests in vivo and 3-O-methylglucose transport into skeletal muscle in vitro to assess glucose tolerance, pancreatic β-cell function, and insulin action in 9- to 11-wk-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). Body weight was slightly higher in the WKY (P < 0.001), while blood pressure was elevated in the SHR (P < 0.001). Insulin responses to intravenous glucose after 4 or 12 h of fasting in SHR were 2–3 times the responses of WKY rats (P < 0.001). The greater insulin responses in SHR were associated with accelerated glucose disappearance P < 0.001 vs. WKY rats). A direct correlation (r = 0.49, P < 0.05) between the peak plasma insulin responses to glucose and Kg values in SHR suggested that the exaggerated insulin responses contributed to the accelerated glucose disappearance in that group. 3-O-methylglucose transport rates into epitrochlearis muscles in vitro did not differ significantly between SHR and WKY groups in the absence of insulin (P < 0.2) or in the presence of insulin at physiological (600 pM, P > 0.4) or pharmacological (120,000 pM, P > 0.9) concentrations. Thus, compared with WKY rats, SHR had exaggerated insulin responses to glucose, similar insulin-mediated glucose transport into skeletal muscle, and enhanced glucose tolerance. Our findings indicate that young, hypertensive SHR have hyperfunction of pancreatic β-cells that is unrelated to insulin resistance. The resultant nutrient-stimulated hyperinsulinemia could play a role in the development or maintenance of elevated blood pressure in SHR.