Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy

DD De Leon, S Deng, R Madani, RS Ahima… - Diabetes, 2003 - Am Diabetes Assoc
Diabetes, 2003Am Diabetes Assoc
A reduction in β-cell mass is an important causative factor in type 1 and type 2 diabetes.
Glucagon-like peptide-1 (GLP-1) and the long-acting agonist exendin 4 (Ex-4) expand β-cell
mass by stimulating neogenesis and proliferation. In the partial pancreatectomy (Ppx)
model, exogenous Ex-4 promotes islet regeneration, leading to sustained improvement in
glucose tolerance. In this study, we investigate the potential role of endogenous GLP-1 in
islet growth. We examined β-cell mass regeneration after 70% Ppx in mice receiving the …
A reduction in β-cell mass is an important causative factor in type 1 and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) and the long-acting agonist exendin 4 (Ex-4) expand β-cell mass by stimulating neogenesis and proliferation. In the partial pancreatectomy (Ppx) model, exogenous Ex-4 promotes islet regeneration, leading to sustained improvement in glucose tolerance. In this study, we investigate the potential role of endogenous GLP-1 in islet growth. We examined β-cell mass regeneration after 70% Ppx in mice receiving the GLP-1 antagonist Ex9-39 and in GLP-1R−/− mice. In Ex9-39–treated sham-operated mice, persistent fasting hyperglycemia was observed, but β-cell mass was not diminished. In pancreatectomized mice, persistent glucose intolerance was noted, but this was not further exacerbated by Ex9-39. Accordingly, β-cell mass recovery of Ppx mice was not impaired by Ex9-39. In contrast, GLP-1R−/− CD1 mice showed worse glucose intolerance after Ppx compared with wild-type CD1 Ppx mice, and this correlated with a significant defect in β-cell mass regeneration. The recovery of β-cell mass differed markedly in the BALB/c and CD1 control mice, indicating a significant role of genetic background in the regulation of β-cell mass. These studies point to a role for endogenous GLP-1 in β-cell regeneration after Ppx in mice.
Am Diabetes Assoc