Beta-cell-specific ablation of the hepatocyte growth factor receptor results in reduced islet size, impaired insulin secretion, and glucose intolerance

Am J Pathol. 2005 Aug;167(2):429-36. doi: 10.1016/s0002-9440(10)62987-2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Blotting, Western
  • Female
  • Genotype
  • Glucose Intolerance*
  • Glucose Transporter Type 2
  • Hyperglycemia / etiology
  • Insulin / metabolism*
  • 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


  • Blood Glucose
  • Glucose Transporter Type 2
  • Insulin
  • Monosaccharide Transport Proteins
  • Proto-Oncogene Proteins c-met
  • Cre recombinase
  • Integrases