Role of H₂-receptors in gastrogenic hyperglycemia and hyperinsulinemia in dogs

Recent studies have demonstrated that an acidified liver meal stimulates insulin release and raises plasma glucose levels. To examine the mechanism of these changes, a liver extract test meal at either pH7 or at pH2 was instilled into the stomach of dogs with a bisected pylorus and a gastric fistula during the infusion of either cimetidine, a specific H₂-receptor antagonist, or a saline control. In response to the meal at pH2 insulin, glucagon and glucose levels rose significantly and were not significantly changed by the infusion of cimetidine. In response to the liver meal at pH7 a late rise in plasma glucagon levels was observed while plasma insulin and glucose did not change significantly; however, during the infusion of cimetidine a significant rise in plasma insulin and glucose levels occurred. The present data suggest that H₂-receptors participate in an inhibitory mechanism with respect to the insulin and glucose response during the gastric phase of a neutral meal, but they do not seem to be involved in the rise in insulin and glucose observed in response to an acidified gastric meal.