Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In glucose homeostasis, glucose concentration is sensed by its metabolism through glucokinase (GCK) and oxidative phosphorylation. Because oxidative phosphorylation is an integral part of the sensory system, glucose sensing is necessarily dependent on oxygen pressure. Much of the dependence on oxygen is suppressed by location of glucose sensing cells in tissues with well-regulated blood flow. In healthy individuals the oxygen dependence is primarily observed in response to transient global hypoxia events such as during birth or transition to high altitude. The GCK sensing system is, however, used to control release of both insulin and glucagon, the preeminant hormonal regulators of blood glucose, as well as glucose sensitive neuronal activity. Suppression of oxygen delivery to glucose-sensing cells or interference with regulation of tissue blood flow by either local or systemic causes, stresses the glucose regulatory system. This is true whether the stress is imposed locally, such as by altered oxygen delivery to the pancreas, or globally, as in pulmonary insufficiency or exposure to high altitude. It may be expected that chronic application of this stress predisposes individuals to developing diabetes. Type 2 diabetes is a broad class of diseases characterized by disturbance of glucose homeostasis, i.e., having either hyperglycemia and/or decreased sensitivity to insulin. Given the role of oxidative phosphorylation in glucose sensing, tissue oxygen deprivation may predispose individuals to developing diabetes as well as contributing to the disease itself. This is particularly true in age-related diabetes because the incidence of vascular insufficiency increases markedly with increasing age. NEW & NOTEWORTHY Glucose sensing requires glucose metabolism through glycolysis and oxidative phosphorylation. Dependence of the latter on oxygen concentration imposes an oxygen dependence on glucose sensing. We have used a validated computational model to quantify that dependence. Evidence is presented that tissue oxygenation plays an important role in predisposition of individuals to developing type 2 diabetes and in progression of the disease.
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PMID:Oxygen dependence of glucose sensing: role in glucose homeostasis and related pathology. 3099 Oct 14

Dependence on opioids and the number of opioid overdose deaths are serious and escalating public health problems, but medication-assisted treatments for opioid addiction remain inadequate for many patients. Glucagon-like pepide-1 (GLP-1) is a gut hormone and neuropeptide with actions in peripheral tissues and in the brain, including regulation of blood glucose and food intake. GLP-1 analogs, which are approved diabetes medications, can reduce the reinforcing and rewarding effects of alcohol, cocaine, amphetamine, and nicotine in rodents. Investigations on effects of GLP-1 analogs on opioid reward and reinforcement have not been reported. We assessed the effects of the GLP-1 receptor agonist Exendin-4 (Ex4) on opioid-related behaviors in male mice, i.e., morphine-conditioned place preference (CPP), intravenous self-administration (IVSA) of the short-acting synthetic opioid remifentanil, naltrexone-precipitated morphine withdrawal, morphine analgesia (male and female mice), and locomotor activity. Ex4 treatment had no effect on morphine-induced CPP, withdrawal, or hyperlocomotion. Ex4 failed to decrease remifentanil self-administration, if anything reinforcing effects of remifentanil appeared increased in Ex4-treated mice relative to saline. Ex4 did not significantly affect analgesia. In contrast, Ex4 dose dependently decreased oral alcohol self-administration, and suppressed spontaneous locomotor activity. Taken together, Ex4 did not attenuate the addiction-related behavioral effects of opioids, indicating that GLP-1 analogs would not be useful medications in the treatment of opioid addiction. This difference between opioids and other drug classes investigated to date may shed light on the mechanism of action of GLP-1 receptor treatment in the addictive effects of alcohol, central stimulants, and nicotine.
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PMID:Glucagon-Like Peptide-1 Receptor Agonist Treatment Does Not Reduce Abuse-Related Effects of Opioid Drugs. 3105 14