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Obesity is an epidemic in Western society, and causes rapidly accelerating rates of type 2 diabetes and cardiovascular disease. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a 'fuel gauge' to monitor cellular energy status. We investigated the potential role of AMPK in the hypothalamus in the(More)
Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function. Leptin stimulates the oxidation of fatty acids and the uptake of glucose, and prevents the accumulation of lipids in nonadipose tissues, which can lead to functional impairments known as "lipotoxicity". The(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 K(ATP) channels in many cell types, including pancreatic beta-cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (K(ATP))(More)
Hypothalamic neurons containing orexin (hypocretin) are activated during motivated behaviors and active waking. We show that injection of orexin-A into the ventromedial hypothalamus (VMH) of mice or rats increased glucose uptake and promoted insulin-induced glucose uptake and glycogen synthesis in skeletal muscle, but not in white adipose tissue, by(More)
Metabolic regulation in mammals requires communication between multiple organs and tissues. The rise in the incidence of obesity and associated metabolic disorders, including type 2 diabetes, has renewed interest in interorgan communication. We used mouse models to explore the mechanism whereby obesity enhances pancreatic beta cell mass, pathophysiological(More)
We studied the effects of microinjection of leptin into the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) on glucose uptake in peripheral tissues in unanesthetized rats. The rate of glucose uptake was assessed in vivo by 2-[3H]deoxyglucose incorporation. Single injection of leptin into VMH increased glucose uptake in brown adipose tissue(More)
We have investigated the adrenergic control of mitogen-activated protein kinase (MAPK) activity in brown adipocytes. Cold exposure in rats led to an activation of MAPK in brown adipose tissue, as determined by the gel mobility shift assay and in-gel kinase assay. In contrast, no activation was seen after surgical sympathetic denervation of the tissue. The(More)
The effects of L-glutamate and insulin on glycogen synthesis in astrocytes were examined. L-Glutamate and insulin both stimulated glycogen synthesis in primary cultures of rat astrocytes in a dose-dependent manner, as measured by the incorporation of 14C from [14C]glucose into glycogen. D-Aspartate also increased the incorporation of 14C into glycogen. When(More)
Ghrelin, an orexigenic hormone, directly activates neuropeptide (NPY) neurons in the hypothalamic arcuate nucleus (ARC), and thereby stimulates food intake. The hypothalamic level of AMP-activated protein kinase (AMPK), an intracellular energy sensor, is activated by peripheral and central administration of ghrelin. We examined whether ghrelin regulates(More)
OBJECTIVE TRPM2 is a Ca²(+)-permeable nonselective cation channel activated by adenosine dinucleotides. We previously demonstrated that TRPM2 is activated by coapplication of heat and intracellular cyclic adenosine 5'-diphosphoribose, which has been suggested to be involved in intracellular Ca²(+) increase in immunocytes and pancreatic β-cells. To clarify(More)