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

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 x 10(6) +/- 0.5 x 10(6); 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.(ABSTRACT TRUNCATED AT 250 WORDS)