TY - JOUR
T1 - The major glucagon-like peptide-1 metabolite, GLP-1-(9-36)-amide, does not affect glucose or insulin levels in mice.
AU - Rolin, Bidda
AU - Deacon, Carolyn F
AU - Carr, Richard D
AU - Ahrén, Bo
N1 - Keywords: Animals; Blood Glucose; Diazoxide; Female; Glucagon-Like Peptide 1; Hypoglycemic Agents; Injections, Intravenous; Insulin; Islets of Langerhans; Mice; Mice, Transgenic; Peptides; Potassium Channels; Receptors, Glucagon
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
U2 - 10.1016/j.ejphar.2004.05.013
DO - 10.1016/j.ejphar.2004.05.013
M3 - Journal article
C2 - 15212985
SN - 0014-2999
VL - 494
SP - 283
EP - 288
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -
