Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy.
A reduction in beta-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 beta-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 beta-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 beta-cell mass was not diminished. In pancreatectomized mice, persistent glucose intolerance was noted, but this was not further exacerbated by Ex9-39. Accordingly, beta-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 beta-cell mass regeneration. The recovery of beta-cell mass differed markedly in the BALB/c and CD1 control mice, indicating a significant role of genetic background in the regulation of beta-cell mass. These studies point to a role for endogenous GLP-1 in beta-cell regeneration after Ppx in mice.
De León
Diva D
DD
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Deng
Shaoping
S
Madani
Reza
R
Ahima
Rexford S
RS
Drucker
Daniel J
DJ
Stoffers
Doris A
DA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005215:Fasting; D005934:Glucagon / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006706:Homeostasis; D006943:Hyperglycemia / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010180:Pancreatectomy; D010446:Peptide Fragments / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011498:Protein Precursors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018027:Receptors, Glucagon / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012038:Regeneration; D013997:Time Factors
D001786:Blood Glucose; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon