The major glucagon-like peptide-1 metabolite, GLP-1-(9-36)-amide, does not affect glucose or insulin levels in mice.
Glucagon-like peptide-1 (GLP-1), a future treatment for type 2 diabetes, is efficiently degraded by the enzyme dipeptidyl peptidase IV (DPP IV), yielding the major metabolite GLP-1-(9-36)-amide. In this study, we examined the potential glucose lowering effect of GLP-1-(9-36)-amide in mice and found that GLP-1-(9-36)-amide (3 and 10 nmol/kg) did not affect insulin secretion or glucose elimination when administered intravenously together with glucose (1 g/kg). This was observed both in normal mice and in transgenic mice having a complete disruption of the signalling from the GLP-1 receptor. Furthermore, after blocking insulin secretion, using diazoxide (25 mg/kg), no effect on insulin-independent glucose disposal of GLP-1-(9-36)-amide was observed. Therefore, GLP-1-(9-36)-amide does not affect glucose disposal in mice either in the presence or absence of intact GLP-1-receptors or in the presence or absence of stimulated insulin levels. This suggests that the GLP-1 metabolite is not involved in the regulation of glucose homeostasis.
Rolin
Bidda
B
Research and Development, Novo Nordisk A/S, Måløv, Denmark. bidr@novonordisk.com
Deacon
Carolyn F
CF
Carr
Richard D
RD
Ahrén
Bo
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003981:Diazoxide / Q000494:pharmacology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood* / Q000502:physiology; D007515:Islets of Langerhans / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists; D018027:Receptors, Glucagon / Q000187:drug effects / Q000235:genetics
D001786:Blood Glucose; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D015221:Potassium Channels; D018027:Receptors, Glucagon; C114437:glucagon-like peptide-1 (9-36)-amide; D052216:Glucagon-Like Peptide 1; D003981:Diazoxide