Matches in UGent Biblio for { ?s ?p beta-Cells from rodents and humans express different receptors recognizing hormones of the secretin-glucagon family, which-when activated-synergize with glucose in the control of insulin release. We have recently reported that isolated islets from mice homozygous for a GLP-1 receptor null mutation (GLP-1R-/-) exhibit a well-preserved insulin-secretory response to glucose. This observation can be interpreted in two different ways: 1) the presence of GLP-1R is not essential for the secretory response of isolated islets to glucose alone; 2) beta-cells in GLP-1R-/- pancreases underwent compensatory changes in response to the null mutation. To explore these possibilities, we studied islets horn control GLP-1R+/+ mice in the absence or presence of 1 mu mol/l exendin (9-39)amide, a specific and potent GLP-1R antagonist. Exendin (9-39)amide (15-min exposure) reduced glucose-induced insulin secretion from both perifused and statically incubated GLP-1R+/+ islets by 50% (P < 0.05), and reduced islet cAMP production in parallel (P < 0.001), Furthermore, GLP-1R-/- islets exhibited: 1) reduced cAMP accumulation in the presence of 20 mmol/l glucose (knockout islets versus control islets, 12 +/- 1 vs. 27 +/- 3 fmol.islet(-1).15 min(-1) P < 0.001) and exaggerated acceleration of cAMP production by 10 nmol/l glucose-dependent insulinotropic peptide (GIP) (increase over 20 mmol/l glucose by GIP in knockout islets versus control islets: 66 +/- 5 vs, 14 +/- 3 fmol.islet(-1).15 min(-1) P < 0.001); 2) increased mean cytosolic [Ca2+] ([Ca2+](c)) at 7, 10, and 15 mmol/l glucose in knockout islets versus control islets; and 3) signs of asynchrony of [Ca2+], oscillations between different islet subregions. In conclusion, disruption of GLP-1R signaling is associated with reduced basal but enhanced GIP-stimulated cAMP production and abnormalities in basal and glucose-stimulated [Ca2+](c). These abnormalities suggest that GLP-1R signaling is an essential upstream component of multiple beta-cell signaling pathways.. }
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- aggregation abstract "beta-Cells from rodents and humans express different receptors recognizing hormones of the secretin-glucagon family, which-when activated-synergize with glucose in the control of insulin release. We have recently reported that isolated islets from mice homozygous for a GLP-1 receptor null mutation (GLP-1R-/-) exhibit a well-preserved insulin-secretory response to glucose. This observation can be interpreted in two different ways: 1) the presence of GLP-1R is not essential for the secretory response of isolated islets to glucose alone; 2) beta-cells in GLP-1R-/- pancreases underwent compensatory changes in response to the null mutation. To explore these possibilities, we studied islets horn control GLP-1R+/+ mice in the absence or presence of 1 mu mol/l exendin (9-39)amide, a specific and potent GLP-1R antagonist. Exendin (9-39)amide (15-min exposure) reduced glucose-induced insulin secretion from both perifused and statically incubated GLP-1R+/+ islets by 50% (P < 0.05), and reduced islet cAMP production in parallel (P < 0.001), Furthermore, GLP-1R-/- islets exhibited: 1) reduced cAMP accumulation in the presence of 20 mmol/l glucose (knockout islets versus control islets, 12 +/- 1 vs. 27 +/- 3 fmol.islet(-1).15 min(-1) P < 0.001) and exaggerated acceleration of cAMP production by 10 nmol/l glucose-dependent insulinotropic peptide (GIP) (increase over 20 mmol/l glucose by GIP in knockout islets versus control islets: 66 +/- 5 vs, 14 +/- 3 fmol.islet(-1).15 min(-1) P < 0.001); 2) increased mean cytosolic [Ca2+] ([Ca2+](c)) at 7, 10, and 15 mmol/l glucose in knockout islets versus control islets; and 3) signs of asynchrony of [Ca2+], oscillations between different islet subregions. In conclusion, disruption of GLP-1R signaling is associated with reduced basal but enhanced GIP-stimulated cAMP production and abnormalities in basal and glucose-stimulated [Ca2+](c). These abnormalities suggest that GLP-1R signaling is an essential upstream component of multiple beta-cell signaling pathways.".