EXHAUSTION OF BLOOD-GLUCOSE RESPONSE AND ENHANCEMENT OF INSULIN-RESPONSE AFTER REPEATED GLUCAGON INJECTIONS IN TYPE-2 DIABETES - POTENTIATION BY PROGRESSIVE HYPERGLYCEMIA

Aims: To investigate the hyperglycemic and insulinemic response to rep eated glucagon injections in Type-2 (non-insulin-dependent) diabetic p atients. Methods: In overnight fasted Type-2 diabetic patients, three i.v. glucagon (1 mg) injections were given as a bolus at two-hour inte rvals. In the hour preceding each glucagon injection, 6 patients recei ved saline and they were tested at near-baseline blood glucose levels, while 8 patients received a glucose-controlled glucose infusion and t hey were tested at increasing blood glucose levels (7.5 +/- 0.2, 12.9 +/- 0.5 and 18.7 +/- 0.7 mmol/l). Blood samples were collected at 0, 3 , 5, 10, 15, 30 and 60 min after each glucagon injection. Results: In the patients tested at near-baseline blood glucose levels, the blood g lucose rise induced by glucagon was smaller after repeated injections. By contrast, the B-cell response to glucagon was well preserved. In t he patients tested at increasing blood glucose levels, the blood gluco se response to glucagon was abolished after repeated injections. By co ntrast, the B-cell response was significantly potentiated. The respect ive areas under the curve of plasma insulin levels in response to gluc agon were 563 +/- 72, 1047 +/- 154 and 1844 +/- 305 m U x 30 min/l (p < 0.001). Conclusion: In Type-2 (non-insulin-dependent) diabetic patie nts, repeated glucagon injections, even when administered in a short ( 4 h) period of time, do not exhaust the B-cell. Endogenous insulin sec retion is even potentiated at increasing blood glucose levels. By cont rast, the hyperglycemic response to glucagon is significantly abolishe d, particularly at high blood glucose levels.