| First Author | Gu L | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 512 |
| Issue | 4 | Pages | 864-870 |
| PubMed ID | 30929915 | Mgi Jnum | J:300651 |
| Mgi Id | MGI:6442269 | Doi | 10.1016/j.bbrc.2019.03.148 |
| Citation | Gu L, et al. (2019) Glucagon receptor antagonism increases mouse pancreatic delta-cell mass through cell proliferation and duct-derived neogenesis. Biochem Biophys Res Commun 512(4):864-870 |
| abstractText | Pancreatic delta-cells, which produce somatostatin, play an indispensable role in glucose homeostasis by inhibiting glucagon and insulin secretion in a paracrine manner. Recent studies have shown that delta-cells are couple with beta-cells to suppress alpha-cell activity. Under certain circumstances, delta-cells could also be trans-differentiated into insulin-producing beta-cells. Thus, pancreatic islet may benefit from delta-cell hyperplasia. However, an effective way to increase delta-cell mass has been rarely reported. Here, we found that REMD 2.59, a human monoclonal antibody and competitive antagonist of the glucagon receptor, massively boosted delta-cell number and increased plasma somatostatin level in both normoglycemic and type 1 diabetic (T1D) mice. The increased delta-cells were due to both delta-cell proliferation and derivation of duct lining cells. Notably, the enlarged delta-cell mass could reduce beta-cell burdens by inducing FoxO1 nuclear translocation in normoglycemic mice. Moreover, some somatostatin-positive cells were co-localized with C-peptide in T1D mice, suggesting that delta-cells might be a source of the newborn beta-cells. Collectively, these observations suggest that treatment with the glucagon receptor monoclonal antibody can increase pancreatic delta-cell mass by promoting self-replication and inducing duct-derived neogenesis both in normoglycemia and diabetic mice. |
