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 first phase of glucose-induced insulin secretion is generally regarded to represent the release of a finite pool of secretion-ready granules, triggered by the depolarization-induced influx of Ca2+ through L-type Ca2+ channels. However, the experimental induction of insulin secretion by imposed plasma membrane depolarization may be more complicated than(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 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 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)
Because of state-based regulation, single-state insurers are subject to oversight by a unique, domiciliary regulator (i.e., regulatory integration), whereas in the case of multi-state insurers, regulatory responsibilities are spread across several regulators (i.e., regulatory separation). In this study, the author draws upon recent theoretical literature(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)