Search Results
You are looking at 1 - 1 of 1 items for
- Author: Geng Tian x
- Refine by access: All content x
Search for other papers by Ida Alenkvist in
Google Scholar
PubMed
Search for other papers by Oleg Dyachok in
Google Scholar
PubMed
Search for other papers by Geng Tian in
Google Scholar
PubMed
Search for other papers by Jia Li in
Google Scholar
PubMed
Search for other papers by Saba Mehrabanfar in
Google Scholar
PubMed
Search for other papers by Yang Jin in
Google Scholar
PubMed
Search for other papers by Bryndis Birnir in
Google Scholar
PubMed
Search for other papers by Anders Tengholm in
Google Scholar
PubMed
Search for other papers by Michael Welsh in
Google Scholar
PubMed
The Src homology-2 domain containing protein B (SHB) has previously been shown to function as a pleiotropic adapter protein, conveying signals from receptor tyrosine kinases to intracellular signaling intermediates. The overexpression of Shb in β-cells promotes β-cell proliferation by increased insulin receptor substrate (IRS) and focal adhesion kinase (FAK) activity, whereas Shb deficiency causes moderate glucose intolerance and impaired first-peak insulin secretion. Using an array of techniques, including live-cell imaging, patch-clamping, immunoblotting, and semi-quantitative PCR, we presently investigated the causes of the abnormal insulin secretory characteristics in Shb-knockout mice. Shb-knockout islets displayed an abnormal signaling signature with increased activities of FAK, IRS, and AKT. β-catenin protein expression was elevated and it showed increased nuclear localization. However, there were no major alterations in the gene expression of various proteins involved in the β-cell secretory machinery. Nor was Shb deficiency associated with changes in glucose-induced ATP generation or cytoplasmic Ca2 + handling. In contrast, the glucose-induced rise in cAMP, known to be important for the insulin secretory response, was delayed in the Shb-knockout compared with WT control. Inhibition of FAK increased the submembrane cAMP concentration, implicating FAK activity in the regulation of insulin exocytosis. In conclusion, Shb deficiency causes a chronic increase in β-cell FAK activity that perturbs the normal insulin secretory characteristics of β-cells, suggesting multi-faceted effects of FAK on insulin secretion depending on the mechanism of FAK activation.
