Impaired compensatory adaption to B-cell mass reduction in young spontaneously hypertensive rats (SHR)

The aim of this study was to examine the effect of insulin resistance on B-cell function and replication. To this end insulin-resistant spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) as a control were subjected to 90% pancreatectomy (Px) or sham operation at the age of 4 weeks. Islet function and regeneration were examined 4 weeks after surgery. Plasma glucose levels were higher in SHR than in WKY 4 weeks after Px (488 +/- 30 vs. 395 +/- 31 mg/dl; p < 0.01). In sham-operated animals, plasma glucose responses to intravenous injections of glucose (0.5 g/kg body weight) were much higher in WKY than in SHR, while plasma insulin responses were greater in SHR than in WKY. There was no insulin response to glucose in either strain of Px rats. In sham-operated rats, the insulin content of the remnant equivalent pancreas (4.6 +/- 0.8 vs. 3.0 +/- 0.3 micrograms; p < 0.05) and whole pancreas (62.2 +/- 2.8 vs. 53.3 +/- 2.1 micrograms; p < 0.05) were greater in SHR than in WKY. However, the insulin content was lower in SHR than in WKY (1.9 +/- 0.3 vs. 2.5 +/- 0.7 micrograms; p < 0.05) 4 weeks after Px. Fibrotic degeneration of pancreatic islets was greater in Px-SHR than in Px-WKY. These data suggest that the B cells of SHR are more vulnerable to reduction of islet mass than those of WKY. A diminished capacity for islet cell regeneration in SHR may be linked to insulin resistance presented in this animal model of hypertension.