Beta-cell function and replication in spontaneously hypertensive rats.

We examined beta-cell function and replication in spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Rats were subjected to 90% pancreatectomy (Px) or sham operation at the age of 8 weeks, and islet function and regeneration were examined 4 weeks after surgery. Plasma glucose levels were higher in SHR than in WKY (509 +/- 38 v 325 +/- 109 mg/dL, P < .0001) 1 week after Px and throughout the experimental period. Plasma glucose responses to intravenous injection of glucose (0.5 g/kg body weight) were not different in the sham-operated animals of the two strains, whereas plasma insulin responses were greater in SHR than in WKY. No insulin responses to glucose were observed in either strain of Px rats. The insulin content of the remnant equivalent (6.7 +/- 2.1 v 4.2 +/- 0.4 micrograms, P < .05) and whole pancreas (156.7 +/- 10.7 v 123.8 +/- 23.5 micrograms, P < .01) in sham-operated rats was greater in SHR than in WKY. However, insulin content was lower (P < .05) in Px-SHR (1.0 +/- 0.2 microgram) than in Px-WKY (3.9 +/- 1.7 micrograms). Histological examination showed that fibrotic degeneration of islets was much greater in Px-SHR than in Px-WKY. These data strongly suggest that the beta cells of SHR were more vulnerable to reduction of islet mass than those of WKY. Our data also suggest that hyperinsulinemia and/or insulin resistance in SHR has a deleterious effect on beta-cell replication.