help button home button Am J Pathol JNCI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dai, C.
Right arrow Articles by Liu, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dai, C.
Right arrow Articles by Liu, Y.
(American Journal of Pathology. 2005;167:429-436.)
© 2005 American Society for Investigative Pathology

ß-Cell-Specific Ablation of the Hepatocyte Growth Factor Receptor Results in Reduced Islet Size, Impaired Insulin Secretion, and Glucose Intolerance

Chunsun Dai*, Chang-Goo Huh{dagger}, Snorri S. Thorgeirsson{dagger} and Youhua Liu*

From the Department of Pathology,* University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and Laboratory of Experimental Carcinogenesis,{dagger} Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Hepatocyte growth factor (HGF) and its c-met receptor consist of a paired signaling system that has been implicated in the regulation of pancreatic ß-cell survival, proliferation, and function. To define the role of HGF/c-met signaling in ß-cell biology in vivo, we have generated conditional knockout mice in which the c-met receptor gene was specifically inactivated in pancreatic ß cells by the Cre-loxP system. Mice with ß-cell-specific deletion of the c-met receptor (ßmet–/–) 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 ß 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 ß cells of ßmet–/– mice. Compared to controls, ßmet–/– 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 ß-cell function, and in maintaining glucose homeostasis.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
M. Johansson, G. Mattsson, A. Andersson, L. Jansson, and P.-O. Carlsson
Islet Endothelial Cells and Pancreatic {beta}-Cell Proliferation: Studies in Vitro and during Pregnancy in Adult Rats
Endocrinology, May 1, 2006; 147(5): 2315 - 2324.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
J.-L. Xia, C. Dai, G. K. Michalopoulos, and Y. Liu
Hepatocyte Growth Factor Attenuates Liver Fibrosis Induced by Bile Duct Ligation
Am. J. Pathol., May 1, 2006; 168(5): 1500 - 1512.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-Y. Lee, M. Ristow, X. Lin, M. F. White, M. A. Magnuson, and L. Hennighausen
RIP-Cre Revisited, Evidence for Impairments of Pancreatic beta-Cell Function
J. Biol. Chem., February 3, 2006; 281(5): 2649 - 2653.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
Y. Li, X. Wen, B. C. Spataro, K. Hu, C. Dai, and Y. Liu
Hepatocyte Growth Factor Is a Downstream Effector that Mediates the Antifibrotic Action of Peroxisome Proliferator-Activated Receptor-{gamma} Agonists
J. Am. Soc. Nephrol., January 1, 2006; 17(1): 54 - 65.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the American Society for Investigative Pathology.