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Although cAMP is well known to regulate exocytosis in many secretory cells, its direct target in the exocytotic machinery is not known. Here we show that cAMP-GEFII, a cAMP sensor, binds to Rim (Rab3-interacting molecule, Rab3 being a small G protein) and to a new isoform, Rim2, both of which are putative regulators of fusion of vesicles to the plasma(More)
cAMP is well known to regulate exocytosis in various secretory cells, but the precise mechanism of its action remains unknown. Here, we examine the role of cAMP signaling in the exocytotic process of insulin granules in pancreatic beta cells. Although activation of cAMP signaling alone does not cause fusion of the granules to the plasma membrane, it clearly(More)
Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in glucose homeostasis, but it is not known how they function in this context. Kir6.2 is the pore-forming subunit of KATP channels in many cell types, including pancreatic β-cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (KATP) channels and(More)
ATP-sensitive potassium (K(ATP)) channels are present in many tissues, including pancreatic islet cells, heart, skeletal muscle, vascular smooth muscle, and brain, in which they couple the cell metabolic state to its membrane potential, playing a crucial role in various cellular functions. The K(ATP) channel is a hetero-octamer comprising two subunits: the(More)
The selective degeneration of dopaminergic (DA) midbrain neurons in the substantia nigra (SN) is a hallmark of Parkinson disease. DA neurons in the neighboring ventral tegmental area (VTA) are significantly less affected. The mechanisms for this differential vulnerability of DA neurons are unknown. We identified selective activation of ATP-sensitive(More)
Epac2, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rap1, is activated by adenosine 3',5'-monophosphate. Fluorescence resonance energy transfer and binding experiments revealed that sulfonylureas, widely used antidiabetic drugs, interact directly with Epac2. Sulfonylureas activated Rap1 specifically through Epac2.(More)
Recently it has been postulated that mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels rather than sarcolemmal K(ATP) (sarcK(ATP)) channels are important as end effectors and/or triggers of ischemic preconditioning (IPC). To define the pathophysiological significance of sarcK(ATP) channels, we conducted functional experiments using Kir6.2-deficient(More)
A 6-bit 3.5-GS/s flash ADC is reported. A load circuit with a clamp diode and a replica-biasing scheme is developed for low-voltage and high-speed operation. An acceleration capacitor is introduced for high-speed overdrive recovery of a comparator. An averaging and interpolation network is employed in this ADC. The interpolation factor is optimized(More)
Physiological and pathophysiological roles of K(ATP) channels have been clarified recently in genetically engineered mice. The Kir6.2-containing K(ATP) channels in pancreatic ss-cells and the hypothalamus are essential in the regulation of glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and are involved in(More)
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, incorporating Kir6.x and sulfonylurea receptor subunits, are weak inward rectifiers that are thought to play a role in neuronal protection from ischemic insults. However, the involvement of Kir6.2-containing KATP channel in hippocampus and neocortex has not been tested directly. To delineate(More)