Here, we investigated the mechanisms linking PAC(1)R to ERK1/2 activation in INS-1E beta-cells and pancreatic islets. PACAP caused a transient (5 min) increase in ERK1/2 phosphorylation via PAC(1)Rs and promoted nuclear translocation of a fraction of cytosolic p-ERK1/2. Both protein kinase A- and Src-dependent pathways mediated this transient ERK1/2 activation. Moreover, PACAP potentiated glucose-induced long-lasting ERK1/2 activation.
Blocking Ca2+ influx abolished glucose-induced AZD1208 ERK1/2 activation and PACAP potentiating effect. Glucose stimulation during KC1 depolarization showed that, in addition to the triggering signal (rise in cytosolic [Ca2+]), the amplifying pathway was also involved in glucose-induced sustained ERK1/2 activation and was required for PACAP potentiation.
The finding that at 30 min glucose-induced p-ERK1/2 was detected in both cytosol and nucleus while the potentiating effect of PACAP was only observed in the cytosol, suggested the involvement of the scaffold protein beta-arrestin. Indeed, beta-arrestin 1 (beta-arr1) depletion (in beta-arr1 GSK2126458 nmr knockout mouse islets or in INS-1E cells by siRNA) completely abolished PACAP potentiation of long-lasting ERK1/2 activation by glucose. Finally, PACAP potentiated glucose-induced CREB transcriptional activity and IRS-2 mRNA expression mainly via the ERK1/2 signaling pathway, and likewise, beta-arr1 depletion reduced the PACAP potentiating effect on IRS-2 expression. These results establish for the first time that PACAP potentiates glucose-induced long-lasting ERK1/2 activation via a beta-arr1-dependent pathway and thus provide new insights concerning the mechanisms of PACAP and glucose actions in pancreatic beta-cells.”
“Colloidal suspensions made up of oppositely charged particles have been shown to self-assemble into substitutionally ordered superlattices. For a given colloidal suspension, the structure of the superlattice formed from self-assembly depends on its composition, charges on the particles, and charge
screening. In this study we have computed the pressure-composition phase diagrams of colloidal suspensions made up of binary mixtures of equal sized and oppositely charged particles interacting via hard core Yukawa potential for varying values GW786034 of charge screening and charge asymmetry. The systems are studied under conditions where the thermal energy is equal or greater in magnitude to the contact energy of the particles and the Debye screening length is smaller than the size of the particles. Our studies show that charge asymmetry has a significant effect on the ability of colloidal suspensions to form substitutionally ordered superlattices. Slight deviations of the charges from the stoichiometric ratio are found to drastically reduce the thermodynamic stability of substitutionally ordered superlattices.