| First Author | Fang Y | Year | 2024 |
| Journal | Cell Metab | Volume | 36 |
| Issue | 6 | Pages | 1237-1251.e4 |
| PubMed ID | 38513648 | Mgi Jnum | J:361382 |
| Mgi Id | MGI:7621050 | Doi | 10.1016/j.cmet.2024.02.012 |
| Citation | Fang Y, et al. (2024) Cytosolic pH is a direct nexus in linking environmental cues with insulin processing and secretion in pancreatic beta cells. Cell Metab |
| abstractText | Pancreatic beta cells actively respond to glucose fluctuations through regulating insulin processing and secretion. However, how this process is elaborately tuned in circumstance of variable microenvironments as well as beta cell-intrinsic states and whether its dysfunction links to metabolic diseases remain largely elusive. Here, we show that the cytosolic pH (pHc) in beta cells is increased upon glucose challenge, which can be sensed by Smad5 via its nucleocytoplasmic shuttling. Lesion of Smad5 in beta cells results in hyperglycemia and glucose intolerance due to insulin processing and secretion deficiency. The role of Smad5 in regulating insulin processing and secretion attributes to its non-canonical function by regulating V-ATPase activity for granule acidification. Genetic mutation of Smad5 or administration of alkaline water to mirror cytosolic alkalization ameliorated glucose intolerance in high-fat diet (HFD)-treated mice. Collectively, our findings suggest that pHc is a direct nexus in linking environmental cues with insulin processing and secretion in beta cells. |
