| First Author | Cheng-Xue R | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 5 | Pages | 1612-22 |
| PubMed ID | 23382449 | Mgi Jnum | J:208552 |
| Mgi Id | MGI:5563702 | Doi | 10.2337/db12-0347 |
| Citation | Cheng-Xue R, et al. (2013) Tolbutamide controls glucagon release from mouse islets differently than glucose: involvement of K(ATP) channels from both alpha-cells and delta-cells. Diabetes 62(5):1612-22 |
| abstractText | We evaluated the role of ATP-sensitive K(+) (K(ATP)) channels, somatostatin, and Zn(2)(+) in the control of glucagon secretion from mouse islets. Switching from 1 to 7 mmol/L glucose inhibited glucagon release. Diazoxide did not reverse the glucagonostatic effect of glucose. Tolbutamide decreased glucagon secretion at 1 mmol/L glucose (G1) but stimulated it at 7 mmol/L glucose (G7). The reduced glucagon secretion produced by high concentrations of tolbutamide or diazoxide, or disruption of K(ATP) channels (Sur1(-/-) mice) at G1 could be inhibited further by G7. Removal of the somatostatin paracrine influence (Sst(-/-) mice or pretreatement with pertussis toxin) strongly increased glucagon release, did not prevent the glucagonostatic effect of G7, and unmasked a marked glucagonotropic effect of tolbutamide. Glucose inhibited glucagon release in the absence of functional K(ATP) channels and somatostatin signaling. Knockout of the Zn(2)(+) transporter ZnT8 (ZnT8(-/-) mice) did not prevent the glucagonostatic effect of glucose. In conclusion, glucose can inhibit glucagon release independently of Zn(2)(+), K(ATP) channels, and somatostatin. Closure of K(ATP) channels controls glucagon secretion by two mechanisms, a direct stimulation of alpha-cells and an indirect inhibition via somatostatin released from delta-cells. The net effect on glucagon release results from a balance between both effects. |
