Active Reaction Sites for Oxygen Reduction in La0.9Sr0.1,MnO3/YSZ Electrodes

Active reaction sites for 02 reduction in La0.~Sr01MnO3 electrode have been characterized by addressing the origin of the cathodic polarization effects on this electrode material. Cathodic polarization (up to - 1.2 V vs. Pt reference electrode} had several effects on O2 reduction kinetics. First, the O2 reduction rate was favorably increased when the perovskite electrode was cathodically polarized. Second, in situ x-ray photoelectron spectroscopy results indicated that the Mn ions are electrochemically reduced and concomitantly the oxygen stoichiometry decreases. Reduction of Mn ions was further demonstrated in the cyclic voltammogram traced under nitrogen atmosphere. Third, hysteresis in cathodic currents was observed in the cyclic voltammograms of the perovskite/YSZ/Pt system, and the hysteresis phenomena were more prominent at higher O~ pressure. We interpreted these findings to mean that the internal and/or external surface oxide vacancies participate in the O2 reduction reaction. However, it has been explained from the Po2-dependent hysteresis phenomena that, even though those surface sites are active in the O2 reduction~ their activity is less than that of the three-phase boundary sites since additional diffusional processes are required for the former sites. Consequently, the three-phase boundary sites are the major reaction sites at lower O2 pressure, which leads to a small hysteresis. However, at higher 02 pressure, the surface sites also participate in the reaction, resulting in a larger hysteresis.Funding for this work was provided by the R&D Management Center for Energy and Resources (Korea). S. M. Oh gratefully acknowledges the financial support from the Alexander yon Humboldt Foundation

Reversible changes in pancreatic islet structure and function produced by elevated blood glucose

Diabetes is characterized by hyperglycaemia due to impaired insulin secretion and aberrant glucagon secretion resulting from changes in pancreatic islet cell function and/or mass. The extent to which hyperglycaemia per se underlies these alterations remains poorly understood. Here we show that β-cell-specific expression of a human activating KATP channel mutation in adult mice leads to rapid diabetes and marked alterations in islet morphology, ultrastructure and gene expression. Chronic hyperglycaemia is associated with a dramatic reduction in insulin-positive cells and an increase in glucagon-positive cells in islets, without alterations in cell turnover. Furthermore, some β-cells begin expressing glucagon, whilst retaining many β-cell characteristics. Hyperglycaemia, rather than KATP channel activation, underlies these changes, as they are prevented by insulin therapy and fully reversed by sulphonylureas. Our data suggest that many changes in islet structure and function associated with diabetes are attributable to hyperglycaemia alone and are reversed when blood glucose is normalized

Unperturbed islet α-cell function examined in mouse pancreas tissue slices

Critical investigation into α-cell biology in health and diabetes has been sparse and at times inconsistent because of the technical difficulties with employing conventional strategies of isolated islets and dispersed single cells. An acute pancreas slice preparation was developed to overcome the enzymatic and mechanical perturbations inherent in conventional islet cell isolation procedures. This preparation preserves intra-islet cellular communication and islet architecture in their in situ native state. α-Cells within tissue slices were directly assessed by patch pipette and electrophysiologically characterized. The identity of the patched cells was confirmed by biocytin dye labelling and immunocytochemistry. α-Cells in mouse pancreas slices exhibited well-described features of INa (excitable at physiological membrane potential), IKATP, small cell size, low resting membrane conductance, and inducible low and high voltage-activated ICa, the latter correlating with exocytosis determined by capacitance measurements. In contrast to previous reports, our large unbiased sampling of α-cells revealed a wide range distribution of all of these parameters, including the amount of KATP conductance, Na+ and Ca2+ current amplitudes, and capacitance changes induced by a train of depolarization pulses. The proposed pancreas slice preparation in combination with standard patch-clamping technique allowed large sampling and rapid assessment of α-cells, which revealed a wide distribution in α-cell ion channel properties. This specific feature explains the apparent inconsistency of previous reports on these α-cell ion channel properties. Our innovative approach will enable future studies into elucidating islet α-cell dysregulation occurring during diabetes

Tolbutamide Controls Glucagon Release From Mouse Islets Differently Than Glucose: Involvement of KATP Channels From Both -Cells and -Cells

We evaluated the role of ATP-sensitive K⁺ (K(ATP)) channels, somatostatin, and Zn²⁺ in the control of glucagon secretion from mouse islets. Switching from 1 to 7 mmol/L glucose inhibited glucagon release. Diazoxide did not reverse the glucagonostatic effect of glucose. Tolbutamide decreased glucagon secretion at 1 mmol/L glucose (G1) but stimulated it at 7 mmol/L glucose (G7). The reduced glucagon secretion produced by high concentrations of tolbutamide or diazoxide, or disruption of K(ATP) channels (Sur1(-/-) mice) at G1 could be inhibited further by G7. Removal of the somatostatin paracrine influence (Sst(-/-) mice or pretreatement with pertussis toxin) strongly increased glucagon release, did not prevent the glucagonostatic effect of G7, and unmasked a marked glucagonotropic effect of tolbutamide. Glucose inhibited glucagon release in the absence of functional K(ATP) channels and somatostatin signaling. Knockout of the Zn²⁺ transporter ZnT8 (ZnT8(-/-) mice) did not prevent the glucagonostatic effect of glucose. In conclusion, glucose can inhibit glucagon release independently of Zn²⁺, K(ATP) channels, and somatostatin. Closure of K(ATP) channels controls glucagon secretion by two mechanisms, a direct stimulation of α-cells and an indirect inhibition via somatostatin released from δ-cells. The net effect on glucagon release results from a balance between both effects