Glucagon receptor antagonism increases mouse pancreatic δ-cell mass through cell proliferation and duct-derived neogenesis.
Biochem Biophys Res Commun
; 512(4): 864-870, 2019 05 14.
Article
em En
| MEDLINE
| ID: mdl-30929915
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 ß-cells to suppress α-cell activity. Under certain circumstances, δ-cells could also be trans-differentiated into insulin-producing ß-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 ß-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 ß-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.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Glucagon
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Células Secretoras de Somatostatina
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Hipoglicemiantes
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Anticorpos Monoclonais
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article