Characterisation of the abnormal pancreatic D and A cell function in streptozotocin diabetic dogs: Studies with D-glyceraldehyde,dihydroxyacetone, D-mannoheptulose,D-glucose,and L-arginine

Summary Pancreatic D and A cell function is deranged in streptozotocin diabetes. To investigate this, the effect of D-glyceraldehyde, dihydroxyacetone, D-mannoheptulose and glucose variations during arginine stimulation on the release of somatostatin and glucagon from the isolated pancreas of normal and streptozotocin diabetic dogs was studied. Concentrations of the trioses, D-glyceraldehyde (1.25 and 2.5 mmol/l) and dihydroxyacetone (11 mmol/l), which normally stimulate D cells, did not influence the release of somatostatin in the diabetic dog. However, the higher concentration of D-glyceraldehyde (5 mmol/l) suppressed D cell secretion in the diabetic animals at 0 and 8.3 mmol/l glucose. A cell secretion was significantly suppressed at the higher glucose level in response to both 2.5 and 5 mmol/l of the triose. This inhibition may be explained by a non-specific effect induced by the high dose of this triose. The addition of 5 mmol/l mannoheptulose, which normally reduces glucose-induced somatostatin secretion and stimulates glucagon release, did not affect hormone secretion. In both the diabetic and the normal animals, arginine (5 mmol/l) stimulated somatostatin and glucagon secretion. Although arginine was able to stimulate D and A cell secretion in the diabetic dogs, it was however unable to restore the response to changes in glucose concentration between 1.4 and 8.3 mmol/l to normal. These results demonstrate that the abnormal pancreatic D and A cell function in streptozotocin diabetes is characterised by an impaired response to glucose and certain glucose metabolites and probably results from a specific defect in glucose recognition.