Exhaustion of blood glucose response and enhancement of insulin response after repeated glucagon injections in type-2 diabetes: potentiation by progressive hyperglycemia.
OBJECTIVE
To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients.


METHODS
In overnight fasted Type-2 diabetic patients, three i.v. glucagon (1 mg) injections were given as a bolus at two-hour intervals. In the hour preceding each glucagon injection, 6 patients received saline and they were tested at near-baseline blood glucose levels, while 8 patients received a glucose-controlled glucose infusion and they 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 glucose rise induced by glucagon was smaller after repeated injections. By contrast, the B-cell response to glucagon was well preserved. In the patients tested at increasing blood glucose levels, the blood glucose response to glucagon was abolished after repeated injections. By contrast, the B-cell response was significantly potentiated. The respective areas under the curve of plasma insulin levels in response to glucagon were 563 +/- 72, 1047 +/- 154 and 1844 +/- 305 m U x 30 min/l (p < 0.001).


CONCLUSIONS
In Type-2 (non-insulin-dependent) diabetic patients, repeated glucagon injections, even when administered in a short (4 h) period of time, do not exhaust the B-cell. Endogenous insulin secretion is even potentiated at increasing blood glucose levels. By contrast, the hyperglycemic response to glucagon is significantly abolished, particularly at high blood glucose levels.
Castillo
M J
MJ
Department of Medicine, C.H.U.-Liège, Belgium.
Scheen
A J
AJ
Paolisso
G
G
Lefebvre
P J
PJ
D000368:Aged; D000704:Analysis of Variance; D001402:B-Lymphocytes / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000473:pathology*; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005765:Gastrointestinal Agents; D007328:Insulin; D005934:Glucagon