PI3K-C2 alpha Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation

Insulin resistance is a syndrome that affects multiple insulin target tissues, each having different biological functions regulated by insulin. A remaining question is to mechanistically explain how an insulin target cell/tissue can be insulin resistant in one biological function and insulin sensitive in another at the same time. Here, we provide evidence that in pancreatic beta cells, knockdown of PI3K-C2 alpha expression results in rerouting of the insulin signal from insulin receptor (IR)-B/PI3K-C2 alpha/PKB-mediated metabolic signaling to IR-B/Shc/ERK-mediated mitogenic signaling, which allows the beta cell to switch from a highly glucose-responsive, differentiated state to a proliferative state. Our data suggest the existence of IR-cascade-selective insulin resistance, which allows rerouting of the insulin signal within the same target cell. Hence, factors involved in the rerouting of the insulin signal represent tentative therapeutic targets in the treatment of insulin resistance.11108Ysciescopu

Measurement of spin asymmetries in the electron impact ionisation of alkali atoms

Baum G, Moede M, Raith W, Schröder W. Measurement of spin asymmetries in the electron impact ionisation of alkali atoms. J.Phys. B. 1985;18(3):531-538

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Re-routing of insulin signalling in response to knockdown of PI3K-C2alpha promotes pancreatic beta cell proliferation

11Nsciescopu

Syntaxin 1 interacts with the L(D) subtype of voltage-gated Ca(2+) channels in pancreatic β cells

Interaction of syntaxin 1 with the α(1D) subunit of the voltage-gated L type Ca(2+) channel was investigated in the pancreatic β cell. Coexpression of the enhanced green fluorescent protein-linked α(1D) subunit with the enhanced blue fluorescent protein-linked syntaxin 1 and Western blot analysis together with subcellular fractionation demonstrated that the α(1D) subunit and syntaxin 1 were colocalized in the plasma membrane. Furthermore, the α(1D) subunit was coimmunoprecipitated efficiently by a polyclonal antibody against syntaxin 1. Syntaxin 1 also played a central role in the modulation of L type Ca(2+) channel activity because there was a faster Ca(2+) current run-down in cells incubated with antisyntaxin 1 compared with controls. In parallel, antisyntaxin 1 markedly reduced insulin release in both intact and permeabilized cells, subsequent to depolarization with K(+) or exposure to high Ca(2+). Exchanging Ca(2+) for Ba(2+) abolished the effect of antisyntaxin 1 on both Ca(2+) channel activity and insulin exocytosis. Moreover, antisyntaxin 1 had no significant effects on Ca(2+)-independent insulin release trigged by hypertonic stimulation. This suggests that there is a structure–function relationship between the α(1D) subunit of the L type Ca(2+) channel and the exocytotic machinery in the pancreatic β cell