Mouse pancreatic beta-cells exhibit preserved glucose competence after disruption of the glucagon-like peptide-1 receptor gene.
Previous work suggested that glucagon-like peptide 1 (GLP-1) can acutely regulate insulin secretion in two ways, 1) by acting as an incretin, causing amplification of glucose-induced insulin release when glucose is given orally as opposed to intravenous glucose injection; and 2) by keeping the beta-cell population in a glucose-competent state. The observation that mice with homozygous disruption of the GLP-1 receptor gene are diabetic with a diminished incretin response to glucose underlines the first function in vivo. Isolated islets of Langerhans from GLP-1 receptor -/- mice were studied to assess the second function in vitro. Absence of pancreatic GLP-1 receptor function was observed in GLP-1 receptor -/- mice, as exemplified by loss of [125I]GLP-1 binding to pancreatic islets in situ and by the lack of GLP-1 potentiation of glucose-induced insulin secretion from perifused islets. Acute glucose competence of the beta-cells, assessed by perifusing islets with stepwise increases of the medium glucose concentration, was well preserved in GLP-1 receptor -/- islets in terms of insulin secretion. Furthermore, neither islet nor total pancreatic insulin content was significantly changed in the GLP-1 receptor -/- mice when compared with age-and sex-matched controls. In conclusion, mouse islets exhibit preserved insulin storage capacity and glucose-dependent insulin secretion despite the loss of functional GLP-1 receptors. The results demonstrate that the glucose responsiveness of islet beta-cells is well preserved in the absence of GLP-1 receptor signaling.
Flamez
D
D
Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
Van Breusegem
A
A
Scrocchi
L A
LA
Quartier
E
E
Pipeleers
D
D
Drucker
D J
DJ
Schuit
F
F
D000818:Animals; D005260:Female; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D009928:Organ Specificity; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018027:Receptors, Glucagon / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose