| First Author | Bauchle CJ | Year | 2021 |
| Journal | Diabetes | Volume | 70 |
| Issue | 8 | Pages | 1717-1728 |
| PubMed ID | 34039628 | Mgi Jnum | J:321877 |
| Mgi Id | MGI:6871826 | Doi | 10.2337/db21-0037 |
| Citation | Bauchle CJ, et al. (2021) Mitochondrial Efflux of Citrate and Isocitrate Is Fully Dispensable for Glucose-Stimulated Insulin Secretion and Pancreatic Islet beta-Cell Function. Diabetes 70(8):1717-1728 |
| abstractText | The defining feature of pancreatic islet beta-cell function is the precise coordination of changes in blood glucose levels with insulin secretion to regulate systemic glucose homeostasis. While ATP has long been heralded as a critical metabolic coupling factor to trigger insulin release, glucose-derived metabolites have been suggested to further amplify fuel-stimulated insulin secretion. The mitochondrial export of citrate and isocitrate through the citrate-isocitrate carrier (CIC) has been suggested to initiate a key pathway that amplifies glucose-stimulated insulin secretion, though the physiological significance of beta-cell CIC-to-glucose homeostasis has not been established. Here, we generated constitutive and adult CIC beta-cell knockout (KO) mice and demonstrate that these animals have normal glucose tolerance, similar responses to diet-induced obesity, and identical insulin secretion responses to various fuel secretagogues. Glucose-stimulated NADPH production was impaired in beta-cell CIC KO islets, whereas glutathione reduction was retained. Furthermore, suppression of the downstream enzyme cytosolic isocitrate dehydrogenase (Idh1) inhibited insulin secretion in wild-type islets but failed to impact beta-cell function in beta-cell CIC KO islets. Our data demonstrate that the mitochondrial CIC is not required for glucose-stimulated insulin secretion and that additional complexities exist for the role of Idh1 and NADPH in the regulation of beta-cell function. |
