Michael Willenborg

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OBJECTIVE The β-cell metabolism of glucose and of some other fuels (e.g. α-ketoisocaproate) generates signals triggering and acutely amplifying insulin secretion. As the pathway coupling metabolism with amplification is largely unknown, we aimed to narrow down the putative amplifying signals. MATERIALS/METHODS An experimental design was used which(More)
The role of plasma membrane depolarization as a determinant of the initial phase of insulin secretion was investigated. NMRI mouse islets and beta-cells were used to measure the kinetics of insulin secretion, ATP and ADP content, membrane potential, and cytosolic free Ca(2+) concentration ([Ca(2+)](i)). The depolarization of metabolically intact beta-cells(More)
Depolarization by a high K(+) concentration is a widely used experimental tool to stimulate insulin secretion. The effects occurring after the initial rise in secretion were investigated here. After the initial peak a fast decline occurred, which was followed by a slowly progressive decrease in secretion when a strong K(+) depolarization was used. At 40 mM(More)
The question whether K⁺ depolarization is an appropriate experimental substitute for the physiological nutrient-induced depolarization of the β-cell plasma membrane was investigated using primary mouse β-cells and islets. At basal glucose 40 mM K⁺ induced a massive monophasic response, whereas 15 mM K⁺ had only a minimal insulinotropic effect, even though(More)
This study examines the conditions under which financial restatements lead corporate boards to dismiss independent auditors and how the market responds to those dismissal announcements. We find that auditors are dismissed at higher than normal rates after restatements, but in contrast to prior research on CEO/CFO turnover, we find no evidence of(More)
We study going-concern (GC) reporting in Belgium to examine the effects associated with a shift toward rules-based audit standards. Beginning in 2000, a major revision in Belgian GC audit standards took effect. Among its changes, auditors must ascertain whether their clients are in compliance with two ‘‘financial-juridical criteria’’ for board of directors’(More)
The contribution of ATP-sensitive K(+) channel (K(ATP) channel)-dependent and -independent signaling to the insulinotropic characteristics of imidazolines was explored using perifused mouse islets and beta-cells. Up to a concentration of 100 muM efaroxan had no insulinotropic effect in the presence of a basal glucose concentration, but enhanced the effect(More)
The K(+) channel blocker, TEA is known to increase action potential amplitude and insulin secretion of mouse beta-cells when added to a nutrient secretagogue. In the presence of a maximally effective sulfonylurea concentration (2.7 microM glipizide) the nutrient secretagogue alpha-ketoisocaproic acid (KIC, 10mM) strongly increased insulin secretion (about(More)
Cytosolic alpha-ketoglutarate is a potential signalling compound at late steps of stimulus-secretion-coupling in the course of insulin secretion induced by glucose and other fuels. This hypothesis is mainly based on the insulin-releasing effect of the membrane permeable ester dimethyl alpha-ketoglutarate which enters the beta-cell and is cleaved to produce(More)
The kinetics of insulin secretion, not just the total amount, is of decisive relevance for the physiological regulation of glucose homeostasis. Thus to characterize the relevant features of the secretory response to an insulinotropic stimulus a method is needed which is able to resolve the temporal response pattern, in particular to distinguish the first(More)