Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Glucokinase is one of four glucose phosphorylating enzymes present in rat liver. Its distinctive features are a high K-m for glucose (high-K-m isozyme) and a rather narrow substrate specificity. In contrast, the other three enzymes, collectively called hexokinases or low-K-m isozymes, exhibit low K-m values for glucose and a wider substrate specificity. 2. Glucokinase is present in the liver os mammals (with some exceptions), amphibians and lower reptiles; It is absent from higher reptiles and birds. The presence or absence of glucokinase may represent an evolutionary adaptation to feeding habits and other physiological peculiarities. Differences in the immunological behavior and in the kinetic parameters of glucokinases from different taxa suggest the operation of divergent evolution. 3. The levels of glucokinase in rat liver depend strictly on the supply of carbohydrate in the diet. Glycogen phosphorylase and glycogen synthetase behave similarly, whereas other carbohydrate-metabolizing enzymes depend on the provision of either protein or protein plus carbohydrate. Glucokinase decays with a half-life of 33 hr when rats are starved or fed a carbohydrate-free diet, and is induced by the administration of glucose. The adaptive character is not exhibited by all mammals, indicating evolutionary discrimination within the same class and even within the same single order Rodentia. Enzyme adaptation in the liver may partially explain the condition known as 'hunger diabetes'. 4. The endocrine system plays a paramount role in glucokinase adaptation, since insulin is essential for glucose-dependent glucokinase induction and, on the other hand, glucagon, catecholamines and cyclic AMP prevent the induction. Glucocorticoids and some pituitary hormones modulate the rate of induction. The mechanisms underlying the hormonal regulation of glucokinase levels are not well known. 5. The variations in liver glucokinase correspond to changes in the amount of enzyme protein as assessed by immunochemical titration. This fact agrees with the effects of inhibitors of protein synthesis on glucokinase induction. 6. An antiserum against rat glucokinase reacts with the enzyme from mammals and turtles but not with the amphibian enzyme. It does not react with low-K-m hexokinases from different sources. 7. The saturation function for glucose is sigmoidal in mammalian and amphibian glucokinases but not in glucokinase from lower reptiles. The Hill's coefficient is very constant with values about 1.6. The K0.5 (concentration for half saturation) values in the different species studied vary between 1.5 and 8 mM. These kinetic parameters may be considered as another adaptive feature aimed to give maximal efficiency to the liver uptake of glucose at the changeable concentrations in the blood resulting from variations in the amount of dietary glucose.
Mol Cell Biochem 1975 Feb 28
PMID:Adaptive character of liver glucokinase. 16 20

Hunger and satiety are complex interplay of several factors in human and animal species. Reduced food intake has also been observed under various pathological conditions. Earlier, we have been able to isolate an endogenous glycoprotein from erythrocyte membranes, which causes anorexia in rats. In the present study, a similar anorexigenic proteoglycan from Mung bean sprout membranes has been isolated and purified. The proteoglycan (50 kDa) consisted of 70-85% carbohydrate with galactose, glucose galactosamine and mannose as the main sugars. Protein part on analysis showed higher glutamic acid and serine content. This proteoglycan reduces food intake when injected in rats deprived of food for 96 hr as well as normally fed rats, mice and rabbits without any rebound. The TCA-soluble proteoglycan from different plant sources have also been compared for their anorexigenic activity. The similarities observed among plant and animal cell membrane proteoglycans with satietins isolated from human blood plasma could be due to membrane origin of satietins.
Mol Cell Biochem 1993 Mar 24
PMID:A novel plant membrane proteoglycan which causes anorexia in animals. 848 51

Recently, Branson and coworkers reported a strong association between binge-eating disorder (BED) and variants in the melanocortin-4 receptor gene (MC4R). In the current study, we compared the eating behavior of 43 obese probands with functionally relevant MC4R mutations and of 35 polymorphism carriers (V103I or I251L) with wild-type carriers. The module for eating disorders of the Composite International Diagnostic Interview was used to identify binge-eating behavior. The Three-Factor Eating Questionnaire and the Leeds Food Frequency Questionnaire were used to assess restrained eating, disinhibition, hunger and percent total energy intake as fat. No significant differences between carriers of MC4R variants and wild-type carriers were detected. In particular, we found no evidence for an increased rate of binge-eating behavior in obese carriers of MC4R variants. Our findings do not support the strong association between BED and MC4R carrier status.
Mol Psychiatry 2004 Aug
PMID:Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations. 1503 65

Calling male toads were tested behaviourally for their prey catching responses to wormlike stimuli and assigned to groups of non-hungry and hungry depending on their prey catching motivation before being prepared for visual unit, massed unit and slow potential shift (SPS) recording from the optic tectum. Control recordings to visual stimuli were made before recording the effects of application of isotonic solutions containing concentrations of 0-41 mM K(+). Application of solution was followed by presentation of the visual stimulus while the solution still bathed the tectum. The best tectal responses were made to large square visual stimuli in the non-hungry toads, perhaps because recordings were made in the breeding season. Responses of the tectum to solution addition were significant in the concentration range of 7-17 mM K(+). Hungry toads showed an earlier, smaller response than non-hungry (sexually motivated) animals. When the visual stimulus was presented, there were unit and massed unit responses at all bathing solution concentrations, which were larger in non-hungry animals. These experiments revealed that toads motivated to feed respond earlier than non-hungry toads to application of artificial CSF to the tectum, though non-hungry toads responded best to the subsequent visual stimulus.
Comp Biochem Physiol A Mol Integr Physiol 2004 Apr
PMID:Tectal responses to potassium loads and subsequent visual stimuli in the toad, Bufo bufo. 1512 74

Hypothalamic neurons that produce the peptide transmitters hypocretins/orexins have attracted much recent attention. They provide direct and predominantly excitatory inputs to all major brain areas except the cerebellum, with the net effect of stimulating wakefulness and arousal. These inputs are essential for generating sustained wakefulness in mammals, and defects in hypocretin signalling result in narcolepsy. In addition, new roles for hypocretins/orexins are emerging in reward-seeking, learning, and memory. Recent studies also indicate that hypocretin/orexin neurons can alter their intrinsic electrical activity according to ambient fluctuations in the levels of nutrients and appetite-regulating hormones. These intriguing electrical responses are perhaps the strongest candidates to date for the elusive neural correlates of after-meal sleepiness and hunger-induced wakefulness. Hypocretin/orexin neurons may thus directly translate rises and falls in body energy levels into different states of consciousness.
J Cell Mol Med
PMID:Metabolic state signalling through central hypocretin/orexin neurons. 1636 91

In the battle to treat the pandemic of obesity, one therapeutic strategy is to block endogenous signals that stimulate appetite and control body weight. One such molecule is ghrelin, a gut peptide that is the only known orexigenic hormone and is a likely contributor to mealtime hunger. The relative importance of ghrelin in long-term body-weight regulation (and thus its promise as an anti-obesity target) is uncertain, however, because genetic and pharmacologic blockade of ghrelin signaling have yielded variable results to date. Using a novel approach of vaccinating rats against their own ghrelin, Zorilla et al. report that animals with high ghrelin-specific antibody titers displayed restricted body weight, without evidence of non-specific inflammation following the vaccine. These results favor a meaningful role for ghrelin in energy homeostasis, hinting at a possible new anti-obesity approach. More broadly, the work of Zorilla et al. supports the feasibility of vaccinations directed against specific autologous targets--immunopharmacotherapy that could potentially be developed to target a wide array of medical conditions.
Mol Interv 2006 Oct
PMID:Prospects for an anti-ghrelin vaccine to treat obesity. 1703 64

The nuclear receptors peroxisome proliferator-activated receptors (PPARs) are known for their critical role in the metabolic syndrome. Here, we show that they are direct regulators of the family of pyruvate dehydrogenase kinase (PDK) genes, whose products act as metabolic homeostats in sensing hunger and satiety levels in key metabolic tissues by modulating the activity of the pyruvate dehydrogenase complex. Mis-regulation of this tightly controlled network may lead to hyperglycemia. In human embryonal kidney cells we found the mRNA expression of PDK2, PDK3 and PDK4 to be under direct primary control of PPAR ligands, and in normal mouse kidney tissue Pdk2 and Pdk4 are PPAR targets. Both, treatment of HEK cells with PPARbeta/delta-specific siRNA and the genetic disruption of the Pparbeta/delta gene in mouse fibroblasts resulted in reduced expression of Pdk genes and abolition of induction by PPARbeta/delta ligands. These findings suggest that PPARbeta/delta is a key regulator of PDK genes, in particular the PDK4/Pdk4 gene. In silico analysis of the human PDK genes revealed two candidate PPAR response elements in the PDK2 gene, five in the PDK3 gene and two in the PDK4 gene, but none in the PDK1 gene. For seven of these sites we could demonstrate both PPARbeta/delta ligand responsiveness in context of their chromatin region and simultaneous association of PPARbeta/delta with its functional partner proteins, such as retinoidXreceptor, co-activator and mediator proteins and phosphorylated RNA polymerase II. In conclusion, PDK2, PDK3 and PDK4 are primary PPARbeta/delta target genes in humans underlining the importance of the receptor in the control of metabolism.
J Mol Biol 2007 Sep 14
PMID:Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of the peroxisome proliferator-activated receptor beta/delta. 1766 20

Accumulating anatomical, functional, and behavioral studies reveal that the cerebellum is involved in the regulation of various visceral functions including feeding control. Cerebellar lesions may induce alterations in feeding behavior and decreases in body weight. Although the exact mechanisms underlying the cerebellar regulation of food intake is still unclear, a series of studies have demonstrated that there are neural pathways directly and/or indirectly connecting the cerebellum with several important centers for feeding control, such as the hypothalamus. Electrophysiological data suggest that via the direct cerebellohypothalamic projections, the cerebellar outputs may reach, converge, and be integrated with some critical feeding signals including gastric vagal afferents, CCK, leptin, and glycemia on single hypothalamic neurons. Furthermore, recent functional imaging studies provide substantial evidences that hunger, satiation, and thirst are accompanied with a cerebellar activation. Here we describe that the cerebellum may be much more than a movement coordinator and actively participate in feeding control, i.e., it may act as an essential node linking somatic and visceral systems and help to generate an integrated and coordinated somatic-visceral response in feeding behavior.
Cell Mol Neurobiol 2008 Jun
PMID:The cerebellum in feeding control: possible function and mechanism. 1802 85

Laboratory studies consistently demonstrate extended lifespan in animals on calorie restriction (CR), where total caloric intake is reduced by 10-40% but adequate nutrition is otherwise maintained. CR has been further shown to delay the onset and severity of chronic diseases associated with aging such as cancer, and to extend the functional health span of important faculties like cognition. Less understood are the underlying mechanisms through which CR might act to induce such alterations. One theory postulates that CR's beneficial effects are intimately tied to the neuroendocrine response to low energy availability, of which the arcuate nucleus in the hypothalamus plays a pivotal role. Neuropeptide Y (NPY), a neurotransmitter in the front line of the arcuate response to low energy availability, is the primary hunger signal affected by CR and therefore may be a critical mechanism for lifespan extension.
Mol Cell Endocrinol 2009 Feb 05
PMID:Hungry for life: How the arcuate nucleus and neuropeptide Y may play a critical role in mediating the benefits of calorie restriction. 1904 66

With the global increase in the epidemic of obesity and type 2 diabetes with a concomitant increase in atherosclerotic disease, an investigation into the effects of various macronutrients and food products has become necessary. Such investigation will allow us to better understand the relationship between the intake of various macronutrients and the pathogenesis of mechanisms underlying the regulation of insulin sensitivity and resistance, oxidative stress and inflammation, the regulation of hunger and satiety and atherogenesis. This review covers the first decade of work in this area relating the intake of usual foods and diets to their immediate and long term outcomes. The review also covers the exciting novel area of anti-inflammatory effects of certain foods. Hopefully, a comprehensive understanding of these actions of macronutrients and their long term effects will allow us to formulate food combinations which will lead to healthy eating habits and improvement in our overall health status.
Exp Mol Med 2010 Apr 30
PMID:Macronutrient intake induces oxidative and inflammatory stress: potential relevance to atherosclerosis and insulin resistance. 2020 Apr 75


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