HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/E1183    most recent 00168.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Annerén, C. Articles by Jansson, L. Search for Related Content PubMed PubMed Citation Articles by Annerén, C. Articles by Jansson, L.

Glucose intolerance and reduced islet blood flow in transgenic mice expressing the FRK tyrosine kinase under the control of the rat insulin promoter

¹Department of Medical Cell Biology, Uppsala University, Uppsala; and ²Department of Cell and Molecular Medicine, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden

Submitted 7 April 2006 ; accepted in final form 8 December 2006

The FRK tyrosine kinase has previously been shown to transduce -cell cytotoxic signals in response to cytokines and streptozotocin and to promote -cell proliferation and an increased -cell mass. We therefore aimed to further evaluate the effects of overexpression of FRK tyrosine kinase in -cells. A transgenic mouse expressing kinase-active FRK under control of the insulin promoter (RIP-FRK) was studied with regard to islet endocrine function and vascular morphology. Mild glucose intolerance develops in RIP-FRK male mice of at least 4 mo of age. This effect is accompanied by reduced glucose-stimulated insulin secretion in vivo and reduced second-phase insulin secretion in response to glucose and arginine upon pancreas perfusion. Islets isolated from the FRK transgenic mice display a glucose-induced insulin secretory response in vitro similar to that of control islets. However, islet blood flow per islet volume is decreased in the FRK transgenic mice. These mice also exhibit a reduced islet capillary lumen diameter as shown by electron microscopy. Total body weight and pancreas weight are not significantly affected, but the -cell mass is increased. The data suggest that long-term expression of active FRK in -cells causes an in vivo insulin-secretory defect, which may be the consequence of islet vascular abnormalities that yield a decreased islet blood flow.

-cells; insulin secretion