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Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized(More)
Insulin secretion in normal B-cells is pulsatile, a consequence of oscillations in the cell membrane potential (MP) and cytosolic calcium activity ([Ca(2+)](c)). We simultaneously monitored glucose-induced changes in [Ca(2+)](c) and in the mitochondrial membrane potential DeltaPsi, as a measure for ATP generation. Increasing the glucose concentration from(More)
Glucocorticoid excess induces hyperglycemia, which may result in diabetes. The present experiments explored whether glucocorticoids trigger apoptosis in insulin-secreting cells. Treatment of mouse beta-cells or INS-1 cells with the glucocorticoid dexamethasone (0.1 micromol/l) over 4 days in cell culture increased the number of fractionated nuclei from 2 to(More)
Diabetes mellitus type 1 and 2 (T1DM and T2DM) are complex multifactorial diseases. Loss of beta-cell function caused by reduced secretory capacity and enhanced apoptosis is a key event in the pathogenesis of both diabetes types. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment of beta-cell function(More)
SUR1(ABCC8)−/− mice lacking functional KATP channels are an appropriate model to test the significance of KATP channels in beta-cell function. We examined how this gene deletion interferes with stimulus-secretion coupling. We tested the influence of metabolic inhibition and galanin, whose mode of action is controversial. Plasma membrane potential (Vm) and(More)
Extracellular recording of the glucose-induced electrical activity of mouse islets of Langerhans on microelectrode arrays (MEAs) is an innovative and powerful tool to address beta-cell (patho-)physiology. In a dual approach we tested whether this technique can detect concentration-dependent drug effects as well as characterize alterations in beta-cell(More)
The membrane potential (V m) of beta-cells oscillates at glucose concentrations between ~6 and 25 mM, i.e. burst phases with action potentials alternate with silent interburst phases generating so-called slow waves. The slow waves drive oscillations of the cytosolic Ca2+ concentration ([Ca2+]c) and insulin secretion. The length of the bursts correlates with(More)
OBJECTIVE Ca(2+)-regulated K(+) channels are involved in numerous Ca(2+)-dependent signaling pathways. In this study, we investigated whether the Ca(2+)-activated K(+) channel of intermediate conductance SK4 (KCa3.1, IK1) plays a physiological role in pancreatic beta-cell function. RESEARCH DESIGN AND METHODS Glucose tolerance and insulin sensitivity were(More)
Islets or beta cells from Sur1 −/− mice were used to determine whether changes in plasma membrane potential (V m) remain coupled to changes in cytosolic Ca2+ ([Ca2+]i) in the absence of KATP channels and thus provide a triggering signal for insulin secretion. The study also sought to elucidate whether [Ca2+]i influences oscillations in V m in sur1−/− beta(More)
In a previous study, we demonstrated that a creatine kinase (CK) modulates KATP channel activity in pancreatic beta cells. To explore phosphotransfer signalling pathways in more detail, we examined whether KATP channel regulation in beta cells is determined by a metabolic interaction between adenylate kinase (AK) and CK. Single channel activity was measured(More)