| First Author | Qiao L | Year | 2022 |
| Journal | Diabetes | Volume | 71 |
| Issue | 5 | Pages | 978-988 |
| PubMed ID | 35147704 | Mgi Jnum | J:324234 |
| Mgi Id | MGI:7266555 | Doi | 10.2337/db21-0923 |
| Citation | Qiao L, et al. (2022) The Essential Role of Pancreatic alpha-Cells in Maternal Metabolic Adaptation to Pregnancy. Diabetes 71(5):978-988 |
| abstractText | Pancreatic alpha-cells are important in maintaining metabolic homeostasis, but their role in regulating maternal metabolic adaptations to pregnancy has not been studied. The objective of this study was to determine whether pancreatic alpha-cells respond to pregnancy and their contribution to maternal metabolic adaptation. With use of C57BL/6 mice, the findings of our study showed that pregnancy induced a significant increase of alpha-cell mass by promoting alpha-cell proliferation that was associated with a transitory increase of maternal serum glucagon concentration in early pregnancy. Maternal pancreatic GLP-1 content also was significantly increased during pregnancy. Using the inducible Cre/loxp technique, we ablated the alpha-cells (alpha-null) before and during pregnancy while maintaining enteroendocrine L-cells and serum GLP-1 in the normal range. In contrast to an improved glucose tolerance test (GTT) before pregnancy, significantly impaired GTT and remarkably higher serum glucose concentrations in the fed state were observed in alpha-null dams. Glucagon receptor antagonism treatment, however, did not affect measures of maternal glucose metabolism, indicating a dispensable role of glucagon receptor signaling in maternal glucose homeostasis. However, the GLP-1 receptor agonist improved insulin production and glucose metabolism of alpha-null dams. Furthermore, GLP-1 receptor antagonist Exendin (9-39) attenuated pregnancy-enhanced insulin secretion and GLP-1 restored glucose-induced insulin secretion of cultured islets from alpha-null dams. Together, these results demonstrate that alpha-cells play an essential role in controlling maternal metabolic adaptation to pregnancy by enhancing insulin secretion. |
