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Diabetes 52:365-371, 2003
© 2003 by the American Diabetes Association, Inc.
Role of Endogenous Glucagon-Like Peptide-1 in Islet Regeneration After Partial Pancreatectomy
1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
2 Division of Endocrinology, Department of Pediatrics, the Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
3 Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
4 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
5 Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
A reduction in ß-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 ß-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 ß-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 ß-cell mass was not diminished. In pancreatectomized mice, persistent glucose intolerance was noted, but this was not further exacerbated by Ex9-39. Accordingly, ß-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 ß-cell mass regeneration. The recovery of ß-cell mass differed markedly in the BALB/c and CD1 control mice, indicating a significant role of genetic background in the regulation of ß-cell mass. These studies point to a role for endogenous GLP-1 in ß-cell regeneration after Ppx in mice.
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