In the pancreas and liver, glucokinase has an important role in regulating glucose homeostasis ( 11). This results in depolarization of the cell and release of hormone via a calcium-dependent mechanism. Metabolism of glucose by glucokinase results in closure of the ATP-sensitive potassium (K ATP) channels. Glucose entry into the cell is via the GLUT-2 transporter ( 15). The mechanism used for the glucose-sensing system is thought to be similar in both β cells and neurons ( 14). Within the β cells and glucose-sensitive neurons glucokinase is part of a glucose-sensing system ( 14). The isoforms have the same kinetic properties but different functions ( 13). The 2 isoforms are produced by the utilization of different promoters. Glucokinase is expressed in 2 isoforms: a hepatic form expressed in the liver and a neuroendocrine form expressed in the pancreas and CNS ( 13). Glucokinase is expressed in the liver, pancreas, and CNS ( 11, 12). Glucokinase is a member of the hexokinase family of enzymes, which phosphorylates glucose to form glucose-6 phosphate ( 11). However, a nontaste-dependent homeostatic mechanism within the hypothalamus or elsewhere in the brain has proved elusive. Evidence suggests that nonhedonic nontaste systems are important in regulating glucose intake ( 9) and that metabolism of glucose is an important factor ( 10). Dopamine is thought to be important in the hedonic response to glucose ( 8). A system regulating glucose intake, driven by hedonic responses generated in the limbic system, has been identified ( 7). The regulation of glucose intake has been studied extensively ( 5, 6). Therefore, a mechanism to detect glucose in food and promote the intake of glucose-rich foods is likely to exist. Although glucose injections into the CNS reduce food intake, glucose is preferred to other types of food by rodents and humans ( 2– 4). It has been suggested that glucose, the brain’s primary fuel source, regulates food intake ( 1). Arcuate nucleus glucokinase activation may represent a CNS mechanism that underlies the oft-described phenomena of the “sweet tooth” and carbohydrate craving. Together, our results suggest that glucokinase activity in the arcuate nucleus specifically regulates glucose intake and that appetite for glucose is an important driver of overall food intake. Additionally, altered glucokinase activity affected release of the orexigenic neurotransmitter neuropeptide Y in response to glucose. Pharmacologic targeting of potential downstream glucokinase effectors revealed that ATP-sensitive potassium channel and P/Q calcium channel activity are required for glucokinase-mediated glucose intake. Moreover, pharmacologic and genetic activation of glucokinase in the arcuate nucleus of rodent models increased glucose ingestion, while decreased arcuate nucleus glucokinase activity reduced glucose intake. In fasted rats, glucokinase activity was specifically increased in the arcuate nucleus but not other regions of the hypothalamus. Here, we determined that glucokinase activity within the hypothalamic arcuate nucleus is involved in regulation of dietary glucose intake. A taste-independent mechanism within the CNS that promotes glucose delivery to the brain has been postulated to maintain glucose homeostasis however, evidence for such a mechanism is lacking. She is currently coordinating a clinical and translational research team at UMIB, and as an endocrinologist she runs a Muldisciplinary Obesity Consultation and a Diabetes and Obesity Clinical Trials Center at Hospital da Luz.The brain relies on a constant supply of glucose, its primary fuel, for optimal function. Bloom, a world reference in gastrointestinal hormones and appetite regulation, where she gained experience in basic research techniques in this area. As a Gulbenkian Foundation Fellow, she was a Visiting Research Fellow at the Department of Metabolic Medicine at Hammersmith Hospital, Imperial College London, directed by Prof. Mariana Monteiro has a particular interest in Diabetes and Obesity, in its clinical and basic research aspects centered on the role of gastro-intestinal hormones in the regulation of glycemic and energy homeostasis. She obtained her PhD in Medicine with a thesis entitled "Mechanisms of gastro-intestinal hormone induced weight loss" from ICBAS, University of Porto, in 2007. She graduated in Medicine in 1996 from the Faculty of Medicine of Porto and completed her specialty in Endocrinology in 2005 at the Hospital de Santo António, Porto. Mariana Monteiro is a Full Professor at the Abel Salazar Institute of Biomedical Sciences (ICBAS) and General Coordinator and Principal Investigator of the Multidisciplinary Biomedical Research Unit (UMÎB) at the University of Porto.
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