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Glucosensing neurons are specialized cells that use glucose as a signaling molecule to alter their action potential frequency in response to variations in ambient glucose levels. Glucokinase (GK) appears to be the primary regulator of most neuronal glucosensing, but other regulators almost certainly exist. Glucose-excited neurons increase their activity(More)
To evaluate potential mechanisms for neuronal glucosensing, fura-2 Ca(2+) imaging and single-cell RT-PCR were carried out in dissociated ventromedial hypothalamic nucleus (VMN) neurons. Glucose-excited (GE) neurons increased and glucose-inhibited (GI) neurons decreased intracellular Ca(2+) ([Ca(2+)](i)) oscillations as glucose increased from 0.5 to 2.5(More)
To test the hypothesis that glucokinase is a critical regulator of neuronal glucosensing, glucokinase activity was increased, using a glucokinase activator drug, or decreased, using RNA interference combined with calcium imaging in freshly dissociated ventromedial hypothalamic nucleus (VMN) neurons or primary ventromedial hypothalamus (VMH; VMN plus arcuate(More)
Specialized neurons utilize glucose as a signaling molecule to alter their firing rate. Glucose-excited (GE) neurons increase and glucose-inhibited (GI) neurons reduce activity as ambient glucose levels rise. Glucose-induced changes in the ATP-to-ADP ratio in GE neurons modulate the activity of the ATP-sensitive K(+) channel, which determines the rate of(More)
Antecedent insulin-induced hypoglycemia (IIH) reduces adrenomedullary responses (AMR) to subsequent bouts of hypoglycemia. The ventromedial hypothalamus [VMH: arcuate (ARC) + ventromedial nuclei] contains glucosensing neurons, which are thought to be mediators of these AMR. Since type 1 diabetes mellitus often begins in childhood, we used juvenile (4- to(More)
G-protein-coupled bile acid receptor 1 (GPBAR1/TGR5/M-Bar/GPR131) is a cell surface receptor involved in the regulation of bile acid metabolism. We have previously shown that Gpbar1-null mice are resistant to cholesterol gallstone disease when fed a lithogenic diet. Other published studies have suggested that Gpbar1 is involved in both energy homeostasis(More)
Applied previously to momentum and heat fluxes, the present study extends the flux-variance method to latent heat and CO2 fluxes in unstable conditions. Scalar similarity is also examined among temperature (θ ), water vapour (q), and CO2 (c). Temperature is adopted as the reference scalar, leading to two feasible strategies to estimate latent heat and CO2(More)
Glucosensing is a property of specialized neurons in the brain that regulate their membrane potential and firing rate as a function of ambient glucose levels. These neurons have several similarities to and -cells in the pancreas, which are also responsive to ambient glucose levels. Many use glucokinase as a rate-limiting step in the production of ATP and(More)
It is now clearly demonstrated that fatty acids (FAs) may modulate neural control of energy homeostasis and specifically affect both insulin secretion and action. Indeed, pancreatic -cells receive rich neural innervation and FAs induce important changes in autonomic nervous activity. We previously reported that chronic infusion of lipids decreased(More)
We report herein the design and synthesis of a series of potent and selective GPR119 agonists. Our objective was to develop a GPR119 agonist with properties that were suitable for fixed-dose combination with a DPP4 inhibitor. Starting from a phenoxy analogue (1), medicinal chemistry efforts directed toward reducing half-life and increasing solubility led to(More)