| First Author | Nomura M | Year | 2014 |
| Journal | Diabetologia | Volume | 57 |
| Issue | 1 | Pages | 157-66 |
| PubMed ID | 24068386 | Mgi Jnum | J:206493 |
| Mgi Id | MGI:5550345 | Doi | 10.1007/s00125-013-3062-2 |
| Citation | Nomura M, et al. (2014) SMAD2 disruption in mouse pancreatic beta cells leads to islet hyperplasia and impaired insulin secretion due to the attenuation of ATP-sensitive K+ channel activity. Diabetologia 57(1):157-66 |
| abstractText | AIMS/HYPOTHESIS: The TGF-beta superfamily of ligands provides important signals for the development of pancreas islets. However, it is not yet known whether the TGF-beta family signalling pathway is required for essential islet functions in the adult pancreas. METHODS: To identify distinct roles for the downstream components of the canonical TGF-beta signalling pathway, a Cre-loxP system was used to disrupt SMAD2, an intracellular transducer of TGF-beta signals, in pancreatic beta cells (i.e. Smad2beta knockout [KO] mice). The activity of ATP-sensitive K(+) channels (KATP channels) was recorded in mutant beta cells using patch-clamp techniques. RESULTS: The Smad2betaKO mice exhibited defective insulin secretion in response to glucose and overt diabetes. Interestingly, disruption of SMAD2 in beta cells was associated with a striking islet hyperplasia and increased pancreatic insulin content, together with defective glucose-responsive insulin secretion. The activity of KATP channels was decreased in mutant beta cells. CONCLUSIONS/INTERPRETATION: These results suggest that in the adult pancreas, TGF-beta signalling through SMAD2 is crucial for not only the determination of beta cell mass but also the maintenance of defining features of mature pancreatic beta cells, and that this involves modulation of KATP channel activity. |
