| First Author | Chen NG | Year | 1995 |
| Journal | Endocrinology | Volume | 136 |
| Issue | 2 | Pages | 505-11 |
| PubMed ID | 7835283 | Mgi Jnum | J:22634 |
| Mgi Id | MGI:70494 | Doi | 10.1210/endo.136.2.7835283 |
| Citation | Chen NG, et al. (1995) Enhanced sensitivity of pancreatic islets from preobese 2-week-old ob/ob mice to neurohormonal stimulation of insulin secretion. Endocrinology 136(2):505-11 |
| abstractText | Insulin secretion from perifused islets of preobese, 2-week-old, genetically obese (ob/ob) mice and their lean littermates was examined to identify early-onset abnormalities in regulation of insulin secretion by ob/ob mice. The ob/ob mice were slightly hyperinsulinemic (+20%) and hypoglycemic (-12%) at 2 weeks of age. Pancreatic islet size, DNA content, and insulin content were similar in ob/ob and lean mice. The responsiveness of islets to glucose, as determined by 20 mM glucose-induced insulin secretion, and the sensitivity of islets to glucose, as determined by the glucose threshold for insulin secretion, were unaffected by phenotype, but two insulin secretagogues that potentiate glucose-induced insulin secretion via activation of the phospholipase-C signal transduction pathway (i.e. acetylcholine, and cholecystokinin) were more effective in stimulating insulin secretion from islets of ob/ob mice than from islets of lean mice. Both responsiveness and sensitivity to acetylcholine and cholecystokinin potentiation of glucose-induced insulin secretion were enhanced in islets from ob/ob mice. Further, glucose-dependent insulinotropic polypeptide, which stimulates glucose-induced insulin secretion via activation of adenylate cyclase, interacted with acetylcholine to further augment differences in insulin secretion between islets from ob/ob and lean mice. The signal transduction pathway common to acetylcholine and cholecystokinin, and cross-talk between this pathway and the glucose-dependent insulinotropic polypeptide signal transduction pathway are loci for early-onset defects in control of insulin secretion from islets of ob/ob mice. |
