Figure 2. (B) Top: schematic of the structure of membrane-targeted SEpHluorin/mCherry chimaera used to measure pH sm . Bottom: confocal images of SEpHluorin (left) and mCherry fluorescence (right) in A431 cells. Bar, 10 µm.

We investigated the effect of oleanolic acid, a plantderived triterpenoid, on insulin secretion and content in pancreatic b-cells and rat islets. Oleanolic acid significantly enhanced insulin secretion at basal and stimulatory glucose concentrations in INS-1 832/13 cells and enhanced acute glucose-stimulated insulin secretion in isolated rat islets. In the cell line the effects of oleanolic acid on insulin secretion were comparable to that of the sulfonylurea tolbutamide at basal glucose levels and with the incretin mimetic Exendin-4 under glucose-stimulated conditions, yet neither Ca 2+ nor cAMP rose in response to oleanolic acid. Chronic treatment with oleanolic acid increased total cellular insulin protein and mRNA levels. These effects may contribute to the anti-diabetic properties of this natural product.

A mutation in pro-EGF causes isolated hypomagnesemia, and monoclonal antibodies targeting the extracellular domain of the EGF receptor (EGFR) affect epithelial Mg 2ϩ transport. The effect of the EGFR tyrosine kinase inhibitor erlotinib on Mg 2ϩ homeostasis, however, remains unknown. Here, we injected C57BL/6 mice with erlotinib for 23 days and observed a small but significant decrease in serum Mg handling but its effect on the systemic Mg 2ϩ concentration seems less potent than that observed with antibody-based EGFR inhibitors. These data suggest that typical human dosages of erlotinib are unlikely to severely affect serum Mg 2ϩ concentrations.

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

In the renal collecting duct, intercalated cells regulate acid-base balance by effluxing protons through the v-H + -ATPase, and bicarbonate via apical pendrin or the basolateral kidney anion exchanger 1 (kAE1). Additionally, collecting duct cells play an essential role in transepithelial absorption of sodium and chloride. Expression of kAE1 in polarized MDCK I cells was previously shown to decrease trans-epithelial electrical resistance (TEER), suggesting a novel role for kAE1 in paracellular permeability. In our study, we not only confirmed that inducible expression of kAE1 in mIMCD3 cells decreased TEER but we also observed (i) increased epithelial absolute permeability to both sodium and chloride, and (ii) that this effect was dependent on kAE1 activity. Further, kAE1 regulated tight junction properties through the tight junction protein claudin-4, a protein with which it physically interacts and colocalizes. These findings unveil a novel interaction between the junctional protein claudin-4 and the kidney anion exchanger, which may be relevant to ion and/or pH homeostasis.