Increase in somatostatin to glucagon ratio in islets of alloxan-diabetic dogs: effect of insulin-induced euglycemia

Abstract

We have previously shown that acute insulin-induced normalization of glycemia in alloxan-diabetic (A-D) dogs results in marked inhibition of total pancreatic glucagon content, but normalization of somatostatin content. We suggested that this glucagon deficiency might account for A-cell unresponsiveness in diabetes. To examine these changes in detail at the islet level, morphometric and immunologic analyses were carried out on pancreata from four normal (N), four hyperglycemic A-D dogs (HD), and four A-D dogs after acute normalization of glycemia with insulin (ND). The total number of islets per pancreas (3.9 × 106 ± 0.5 × 106; determined from the number of islets per square millimetre) was reduced by 60% (p < 0.001) in HD, and this was not affected by acute normalization of glycemia. Insulin content per islet was 1247 ± 205 pg in N, and this was reduced in both HD and ND to 2 and 5%, respectively (p < 0.001). Similarly, insulin-containing B-cell area was 76 ± 1% of the total islet area in N, and was unmeasurable in HD and ND. Glucagon content per islet was 89 ± 6 pg in N, and this was increased by 215% (p < 0.001) in HD, but was normalized in ND. The A-cell area increased concomitantly by 170% from 17 ±1 to 46 ± 2% (p < 0.01) of islet area in HD, and remained elevated in ND. In contrast, somatostatin content per islet was 3.0 ± 1.1 pg in N, but was increased by 567% (p < 0.01) in HD and fell to 200% (p = ns) of N in ND. D-cell area increased by 55% in HD, from 11.5 ± 0.8 to 17.8 ± 0.9% (p < 0.01), and remained elevated at 15.6 ± 1.1% (p < 0.01) in ND. The ratio of somatostatin to glucagon content in the islet was therefore 0.03 ± 0.01 in N, and this was increased by 167 (p = ns) and 333% (p < 0.05) in HD and ND, respectively. We speculate that the increase in the islet somatostatin to glucagon ratio in normoglycemic diabetic dogs may play a role in the suppression of glucagon responses in diabetes.Key words: islet, glucagon, somatostatin, diabetes, insulin-induced euglycemia.