| First Author | Vlacich G | Year | 2010 |
| Journal | Islets | Volume | 2 |
| Issue | 5 | Pages | 308-17 |
| PubMed ID | 21099329 | Mgi Jnum | J:177239 |
| Mgi Id | MGI:5294526 | Doi | 10.4161/isl.2.5.13058 |
| Citation | Vlacich G, et al. (2010) Pim3 negatively regulates glucose-stimulated insulin secretion. Islets 2(5):308-17 |
| abstractText | Pancreatic beta-cell response to glucose stimulation is governed by tightly regulated signaling pathways which have not been fully characterized. A screen for novel signaling intermediates identified Pim3 as a glucose-responsive gene in the beta cell, and here, we characterize its role in the regulation of beta-cell function. Pim3 expression in the beta-cell was first observed through microarray analysis on glucose-stimulated murine insulinoma (MIN6) cells where expression was strongly and transiently induced. In the pancreas, Pim3 expression exhibited similar dynamics and was restricted to the beta cell. Perturbation of Pim3 function resulted in enhanced glucose-stimulated insulin secretion, both in MIN6 cells and in isolated islets from Pim3-/- mice, where the augmentation was specifically seen in the second phase of secretion. Consequently, Pim3-/- mice displayed an increased glucose tolerance in vivo. Interestingly, Pim3-/- mice also exhibited increased insulin sensitivity. Glucose stimulation of isolated Pim3-/- islets resulted in increased phosphorylation of ERK1/2, a kinase involved in regulating beta-cell response to glucose. Pim3 was also found to physically interact with SOCS6 and SOCS6 levels were strongly reduced in Pim3-/- islets. Overexpression of SOCS6 inhibited glucose-induced ERK1/2 activation, strongly suggesting that Pim3 regulates ERK1/2 activity through SOCS6. These data reveal that Pim3 is a novel glucose-responsive gene in the beta cell that negatively regulates insulin secretion by inhibiting the activation of ERK1/2, and through its effect on insulin sensitivity, has potentially a more global function in glucose homeostasis. |
