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 g lycemia 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 detai l at the islet level, morphometric and immunologic analyses were carri ed out on pancreata from four normal (N), four hyperglycemic A-D dogs (HD), and four A-D dogs after acute normalization of glycemia with ins ulin (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 ac ute 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%, respe ctively (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 N D. Glucagon content per islet was 89 +/- 6 pg in N, and this was incre ased by 215 % (p < 0.00 1) 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 incre ased 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 there fore 0.03 +/- 0.01 in N, and this was increased by 167 (p = ns) and 33 3 % (p < 0.05) in HD and ND, respectively. We speculate that the incre ase in the islet somatostatin to glucagon ratio in normoglycemic diabe tic dogs may play a role in the suppression of glucagon responses in d iabetes.