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Glucagon receptor antagonism increases mouse pancreatic δ-cell mass through cell proliferation and duct-derived neogenesis.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2019 May 14; Vol. 512 (4), pp. 864-870. Date of Electronic Publication: 2019 Mar 28. - Publication Year :
- 2019
-
Abstract
- Pancreatic δ-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 δ-cells are couple with β-cells to suppress α-cell activity. Under certain circumstances, δ-cells could also be trans-differentiated into insulin-producing β-cells. Thus, pancreatic islet may benefit from δ-cell hyperplasia. However, an effective way to increase δ-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 δ-cell number and increased plasma somatostatin level in both normoglycemic and type 1 diabetic (T1D) mice. The increased δ-cells were due to both δ-cell proliferation and derivation of duct lining cells. Notably, the enlarged δ-cell mass could reduce β-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 δ-cells might be a source of the newborn β-cells. Collectively, these observations suggest that treatment with the glucagon receptor monoclonal antibody can increase pancreatic δ-cell mass by promoting self-replication and inducing duct-derived neogenesis both in normoglycemia and diabetic mice.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Animals, Newborn
Cell Proliferation drug effects
Cell Shape
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Experimental pathology
Diabetes Mellitus, Type 1 drug therapy
Diabetes Mellitus, Type 1 metabolism
Diabetes Mellitus, Type 1 pathology
Glucagon blood
Humans
Insulin blood
Mice, Inbred C57BL
Somatostatin blood
Somatostatin-Secreting Cells drug effects
Antibodies, Monoclonal pharmacology
Hypoglycemic Agents pharmacology
Receptors, Glucagon antagonists & inhibitors
Somatostatin-Secreting Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 512
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 30929915
- Full Text :
- https://doi.org/10.1016/j.bbrc.2019.03.148