Glucose intolerance and reduced islet blood flow in transgenic mice expressing the FRK tyrosine kinase under the control of the rat insulin promoter
2007 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 292, no 4, E1183-E1190 p.Article in journal (Refereed) Published
The FRK tyrosine kinase has previously been shown to transduce β-cell cytotoxic signals in response to cytokines and streptozotocin and to promote β-cell proliferation and an increased β-cell mass. We therefore aimed to further evaluate the effects of overexpression of FRK tyrosine kinase in β-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 β-cell mass is increased. The data suggest that long-term expression of active FRK in β-cells causes an in vivo insulin-secretory defect, which may be the consequence of islet vascular abnormalities that yield a decreased islet blood flow.
Place, publisher, year, edition, pages
2007. Vol. 292, no 4, E1183-E1190 p.
β-cells, Insulin secretion
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-13519DOI: 10.1152/ajpendo.00168.2006ISI: 000245361800024PubMedID: 17179392OAI: oai:DiVA.org:uu-13519DiVA: diva2:41289