Insulin requirement for the antihyperglycaemic effect of metformin.
1. Insulin-dependent diabetic BB/S rats with little or no endogenous insulin were used to determine whether insulin is required for the acute antihyperglycaemic effect of metformin (dimethylbiguanide). 2. Metformin (250 mg kg-1, intrajejunally) did not lower the hyperglycaemia in BB/S rats in the absence of exogenous insulin, but metformin increased by 69% (P < 0.05) the blood glucose-lowering effect of exogenous insulin. 3. Metformin (250 mg kg-1, intrajejunally) improved glucose disposal in rats with a normal insulin response to an intravenous glucose challenge. Plasma glucose disappearance was increased from 0.7 +/- 0.1 to 2.5 +/- 0.1% min-1 (P < 0.05). 3. When the insulin response to glucose was suppressed with somatostatin and diazoxide, metformin improved glucose disposal to a similar extent to that in rats with a normal insulin response. Plasma glucose disappearance was increased from 0.24 +/- 0.02 to 1.0 +/- 0.1% min-1 (P < 0.01). 5. The results indicate that insulin is required for the acute antihyperglycaemic effect of metformin, but the extent of this effect is not proportional to the prevailing insulin concentration.
Bailey
C J
CJ
Department of Pharmaceutical and Biological Sciences, Aston University, Birmingham.
Mynett
K J
KJ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D005947:Glucose / Q000008:administration & dosage; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007328:Insulin / Q000494:pharmacology* / Q000502:physiology*; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D008687:Metformin; D005947:Glucose