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- 7Chan, Catherine B.
- 7Wheeler, Michael B.
- 4Koshkin, Vasilij
- 2Dai, Feihan F.
- 2Joseph, Jamie W.
- 2Saleh, Monique C.
Inhibition of Kv2.1 voltage-dependent K+ channels in pancreatic ß-cells enhances glucose-dependent insulin secretionDownload
Chan, Catherine B., Wang, Jianli, Sakellaropoulos, George, Tsushima, Robert G., Joseph, Jamie W., Smukler, Simon R., Sewing, Sabine, Saleh, Monique C., Wang, Jing, Salapatek, Anne Marie F., Wheeler, Michael B., MacDonald, Patrick E.
Voltage-dependent (Kv) outward K+ currents repolarize β-cell action potentials during a glucose stimulus to limit Ca2+ entry and insulin secretion. Dominant-negative “knockout” of Kv2 family channels enhances glucose-stimulated insulin secretion. Here we show that a putative Kv2.1 antagonist...
Excessive free fatty acid (FFA) exposure represents a potentially important diabetogenic condition that can impair insulin secretion from pancreatic β-cells. Because mitochondrial oxidative phosphorylation is a main link between glucose metabolism and insulin secretion, in the present work we...
The characterization of mitochondrial permeability transition (MPT) in clonal pancreatic beta cells: Multiple modes and regulationDownload
Mitochondrial permeability transition (MPT), which contributes substantially to the regulation of normal mitochondrial metabolism, also plays a crucial role in the initiation of cell death. It is known that MPT is regulated in a tissue-specific manner. The importance of MPT in the pancreatic...
Chronic exposure to elevated free fatty acids (lipotoxicity) induces uncoupling protein (UCP2) in the pancreatic β-cell, and therefore a causal link between UCP2 and β-cell defects associated with obesity may exist. Recently, we showed that lipid treatment in vivo and in vitro in UCP2(–/–)...
The insulin receptor (IR) and its signaling appear to be essential for insulin secretion from pancreatic β-cells. However, much less is known about the role of the IR in α-cells. To assess the role of the IR in glucagon and insulin secretion, we engineered adeno-viruses for high efficiency small...
A member of the neuronal Ca2+-sensor protein family visinin-like-protein-1 (vilip-1) is expressed in pancreatic β-cells and regulates insulin secretion and biosynthesisDownload
Visinin-like protein-1 (VILIP-1) is a member of the neuronal Ca2+ sensor protein family that modulates Ca2+-dependent cell signaling events. VILIP-1, which is expressed primarily in the brain, increases cAMP formation in neural cells by modulating adenylyl cyclase, but its functional role in...
Limited mitochondrial permeabilization is an early manifestation of palmitate-induced lipotoxicity in pancreatic ß-cellsDownload
Involvement of the mitochondrial permeability transition (MPT) pore in early stages of lipotoxic stress in the pancreatic β-cell lines MIN6 and INS-1 was the focus of this study. Both long term (indirect) and acute (direct) effects of fatty acid (FA) application on β-cell susceptibility to...