| First Author | Huang WQ | Year | 2017 |
| Journal | Front Physiol | Volume | 8 |
| Pages | 835 | PubMed ID | 29204121 |
| Mgi Jnum | J:321311 | Mgi Id | MGI:6819042 |
| Doi | 10.3389/fphys.2017.00835 | Citation | Huang WQ, et al. (2017) Abnormal CFTR Affects Glucagon Production by Islet alpha Cells in Cystic Fibrosis and Polycystic Ovarian Syndrome. Front Physiol 8:835 |
| abstractText | Glucagon, produced by islet alpha cells, functions to increase blood glucose. Abnormal glucose levels are often seen in cystic fibrosis (CF), a systematic disease caused by mutations of the CF transmembrane conductance regulator (CFTR), and in polycystic ovarian syndrome (PCOS), an endocrine disorder featured with hyperandrogenism affecting 5-10% women of reproductive age. Here, we explored the role of CFTR in glucagon production in alpha cells and its possible contribution to glucagon disturbance in CF and PCOS. We found elevated fasting glucagon levels in CFTR mutant (DF508) mice compared to the wildtypes. Glucagon and prohormone convertase 2 (PC2) were also upregulated in CFTR inhibitor-treated or DF508 islets, as compared to the controls or wildtypes, respectively. Dihydrotestosterone (DHT)-induced PCOS rats exhibited significantly lower fasting glucagon levels with higher CFTR expression in alpha cells compared to that of controls. Treatment of mouse islets or alphaTC1-9 cells with DHT enhanced CFTR expression and reduced the levels of glucagon and PC2. The inhibitory effect of DHT on glucagon production was blocked by CFTR inhibitors in mouse islets, and mimicked by overexpressing CFTR in alphaTC1-9 cells with reduced phosphorylation of the cAMP/Ca(2+) response element binding protein (p-CREB), a key transcription factor for glucagon and PC2. These results revealed a previously undefined role of CFTR in suppressing glucagon production in alpha-cells, defects in which may contribute to glucose metabolic disorder seen in CF and PCOS. |
