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PMID:16049329

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Citation

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

Abstract

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.

Links

PubMed PMC1603568

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MET

acts_upstream_of_or_within

GO:0010828: positive regulation of glucose transmembrane transport

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176227,MGI:MGI:3041135

P

  • regulates_o_occurs_in:(CL:0000169)
  • regulates_o_occurs_in:(EMAPA:32927)

Seeded From UniProt

complete

MOUSE:MET

acts_upstream_of_or_within

GO:0042593: glucose homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176227,MGI:MGI:3041135

P

Seeded From UniProt

complete

MOUSE:MET

acts_upstream_of_or_within

GO:0010828: positive regulation of glucose transmembrane transport

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2176227,MGI:MGI:3041135

P

  • regulates_o_occurs_in:(EMAPA:32927)
  • regulates_o_occurs_in:(CL:0000169)

Seeded From UniProt

complete


See also

References

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