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Intracellular Ca2+ levels were monitored in single, acutely isolated mouse islets of Langerhans by dual emission Indo-1 fluorometry. High-frequency (3.1 min-1) [Ca2+]i oscillations with a brief rising time (1-2 s) and 10 s half-width ('fast' oscillations) were detected in 11 mM glucose. Raising the glucose concentration to 16.7 mM increased the duration of(More)
Buffered Ca(2+) diffusion in the cytosol of neuroendocrine cells is a plausible explanation for the slowness and latency in the secretion of hormones. We have developed a Monte Carlo simulation to treat the problem of 3-D diffusion and kinetic reactions of ions and buffers. The 3-D diffusion is modeled as a random walk process that follows the path of each(More)
1. Pancreatic beta-cells oscillate synchronously when grouped in islets. Coupling seems essential to maintain this oscillatory behaviour, as isolated cells are unable to oscillate. This allows the islet to be used as a model system for studying the role of coupling in the generation of oscillatory patterns. 2. Pairs of beta-cells were intracellularly(More)
1. The electrical responses of nociceptive (N) lateral and N medial neurons of the leech segmental ganglion to mechanical, chemical, and thermal stimulation of the skin were studied in a superfused ganglion-body wall preparation. 2. Mechanical indentation of the skin > 10 mN evoked in both types of cells a sustained discharge of impulses; afterdischarge was(More)
Glucagon, secreted from pancreatic alpha-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In(More)
Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem(More)
Pancreatic beta cells, tightly organized in the islet of Langerhans, secrete insulin in response to glucose in a calcium-dependent manner. The calcium input required for this secretory activity is thought to be provided by an oscillatory electrical activity occurring in the form of "bursts" of calcium action potentials. The previous observation that islet(More)
Extracellular signalling cues play a major role in the activation of differentiation programmes. Mouse embryonic stem (ES) cells are pluripotent and can differentiate into a wide variety of specialized cells. Recently, protocols designed to induce endocrine pancreatic differentiation in vitro have been designed but little information is currently available(More)
Impaired insulin secretion is a hallmark in both type I and type II diabetic individuals. Whereas type I (insulin-dependent diabetes mellitus) implies ss-cell destruction, type II (non-insulin dependent diabetes mellitus), responsible for 75% of diabetic syndromes, involves diminished glucose-dependent secretion of insulin from pancreatic beta-cells.(More)
S. Bordin and colleagues have proposed that the depolarizing effects of acetylcholine and other muscarinic agonists on pancreatic beta-cells are mediated by a calcium release-activated current (CRAC). We support this hypothesis with additional data, and present a theoretical model which accounts for most known data on muscarinic effects. Additional(More)