TableEdit

Dai, C, Huh, CG, Thorgeirsson, SS and Liu, Y (2005) Beta-cell-specific ablation of the hepatocyte growth factor receptor results in reduced islet size, impaired insulin secretion, and glucose intolerance. Am. J. Pathol. 167:429-36

Hepatocyte growth factor (HGF) and its c-met receptor consist of a paired signaling system that has been implicated in the regulation of pancreatic beta-cell survival, proliferation, and function. To define the role of HGF/c-met signaling in beta-cell biology in vivo, we have generated conditional knockout mice in which the c-met receptor gene was specifically inactivated in pancreatic beta cells by the Cre-loxP system. Mice with beta-cell-specific deletion of the c-met receptor (betamet-/-) displayed slight growth retardation, mild hyperglycemia, and decreased serum insulin levels at 6 months of age when compared with their control littermates. Deficiency of the c-met receptor in beta cells resulted in a complete loss of acute-phase insulin secretion in response to glucose and an impaired glucose tolerance. Glucose transporter-2 expression was down-regulated in the beta cells of betamet-/- mice. Compared to controls, betamet-/- mice exhibited reduced islet size and decreased insulin content in the pancreas, but displayed normal islet morphology. Therefore, HGF/c-met signaling plays an imperative role in controlling islet growth, in regulating beta-cell function, and in maintaining glucose homeostasis.

PubMed PMC1603568

Animals; Blood Glucose/metabolism; Blotting, Western; Female; Genotype; Glucose Intolerance; Glucose Transporter Type 2; Hyperglycemia/etiology; Insulin/secretion; Integrases; Islets of Langerhans/metabolism; Islets of Langerhans/pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Monosaccharide Transport Proteins/metabolism; Proto-Oncogene Proteins c-met/genetics; Proto-Oncogene Proteins c-met/physiology; Reverse Transcriptase Polymerase Chain Reaction