| First Author | Saleh M | Year | 2021 |
| Journal | J Biol Chem | Volume | 297 |
| Issue | 5 | Pages | 101235 |
| PubMed ID | 34582892 | Mgi Jnum | J:331906 |
| Mgi Id | MGI:7386960 | Doi | 10.1016/j.jbc.2021.101235 |
| Citation | Saleh M, et al. (2021) beta-cell Smad2 null mice have improved beta-cell function and are protected from diet-induced hyperglycemia. J Biol Chem 297(5):101235 |
| abstractText | Understanding signaling pathways that regulate pancreatic beta-cell function to produce, store, and release insulin, as well as pathways that control beta-cell proliferation, is vital to find new treatments for diabetes mellitus. Transforming growth factor-beta (TGF-beta) signaling is involved in a broad range of beta-cell functions. The canonical TGF-beta signaling pathway functions through intracellular smads, including smad2 and smad3, to regulate cell development, proliferation, differentiation, and function in many organs. Here, we demonstrate the role of TGF-beta/smad2 signaling in regulating mature beta-cell proliferation and function using beta-cell-specific smad2 null mutant mice. beta-cell-specific smad2-deficient mice exhibited improved glucose clearance as demonstrated by glucose tolerance testing, enhanced in vivo and ex vivo glucose-stimulated insulin secretion, and increased beta-cell mass and proliferation. Furthermore, when these mice were fed a high-fat diet to induce hyperglycemia, they again showed improved glucose tolerance, insulin secretion, and insulin sensitivity. In addition, ex vivo analysis of smad2-deficient islets showed that they displayed increased glucose-stimulated insulin secretion and upregulation of genes involved in insulin synthesis and insulin secretion. Thus, we conclude that smad2 could represent an attractive therapeutic target for type 2 diabetes mellitus. |
