Increased insulin secretion and normalization of glucose tolerance by cholinergic agonism in high fat-fed mice.
Increased insulinotropic activity by the cholinergic agonist carbachol exists in insulin-resistant high fat-fed C57BL/6J mice. We examined the efficiency and potency of carbachol to potentiate glucose-stimulated insulin secretion and to improve glucose tolerance in these animals. Intravenous administration of carbachol (at 15 and 50 nmol/kg) markedly potentiated glucose (1 g/kg)-stimulated insulin secretion in mice fed both a control and a high-fat diet (for 12 wk), with a higher relative potentiation in high fat-fed mice measured as increased (1-5 min) acute insulin response and area under the 50-min insulin curve. Concomitantly, glucose tolerance was improved by carbachol. In fact, carbachol normalized glucose-stimulated insulin secretion and glucose tolerance in mice subjected to a high-fat diet. Carbachol (>100 nmol/l) also potentiated glucose-stimulated insulin secretion from isolated islets with higher efficiency in high fat-fed mice. In contrast, binding of the muscarinic receptor antagonist [N-methyl-(3)H]scopolamine to islet muscarinic receptors and the contractile action of carbachol on ileum muscle strips were not different between the two groups. We conclude that carbachol normalizes glucose tolerance in insulin resistance.
Ahrén
B
B
Department of Medicine, Lund University, S-205 02 Malmö, Sweden. Bo.Ahren@medforsk.mas.lu.se
Sauerberg
P
P
Thomsen
C
C
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002217:Carbachol / Q000378:metabolism / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012016:Reference Values
D001786:Blood Glucose; D018679:Cholinergic Agonists; D004041:Dietary Fats; D007328:Insulin; D002217:Carbachol; D005947:Glucose