Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020175 (hunger)
 5,670 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.
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PMID:Adaptive character of liver glucokinase. 16 20

Rats that were made diabetic by the subcutaneous injection of alloxan monohydrate were found to be resistant to the anorexic action of d-amphetamine. This resistance to amphetamine anorexia did not appear attributable to an increased hunger motivation of the diabetic rats, but rather seemed due to a diminished action of the drug in alloxan-injected animals. This conclusion was supported by further experiments indicating that alloxan-injected rats show diminished locomotor activity and stereotyped behavior following amphetamine administration. Furthermore, the amphetamine resistance appears to be the result of the diabetic state, since amphetamine-induced stereotyped behavior could be reinstated in alloxan-injected rats by the administration of protamine zinc insulin for ten days. The results of these investigations suggest that there exists an altered central nervous system response to d-amphetamine in the diabetic rat. These possibility of an abnormal functioning of central catecholamine-containing neurons in such animals is discussed.
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PMID:Further analysis of the resistance of the diabetic rat to d-amphetamine. 56 33

Lipoatrophic diabetes has been produced in rabbits by injection of a fraction prepared from the urine from patients with congenital generalized lipodystrophy. Both these conditions are considered to be hypothalamic syndromes. The animals, and a patient with congenital generalized lipodystrophy and latent diabetes were treated with the dopamine receptor blocker, pimozide, for 4 and 17 months, respectively. The results were discouraging even though the patient got a daily dose of 16 mg pimozide. Fenfluramine has a lowering effect on brain serotonin, and peripheral effects on glucose and triglyceride metabolism. This drug improved the general condition of the rabbits with lipoatrophic diabetes, as well as that of the patient with congenital generalized lipodystrophy. The rabbits became normoglycaemic and insulin sensitive. In the patient a normalization of the urinary excretion of the serotonin metabolite 5-OH-indole acetic acid was observed. His voracious hunger and profuse perspiration were reduced, the hyperkeratotic layer of the skin peeled off, and the pigmentations of the skin decreased. There was observed an improvement of ALAT and ASAT, normalization of the fasting blood glucose, and increased sensitivity to exogenous insulin. After 11 months of 200 mg fenfluramine daily addtitional administration of 2 g clofibrate per day produced normalization of the serum triglyceride concentration and a marked reduction of the resistance to insulin. Three more patients with congenital generalized lipodystriphy, two of whom have manifest diabetes, have now started treatment with fenfluramine and are improving. The rabbits got relapse of their lipoatrophic diabetes when the fenfluramine treatment was stopped. It is suggested that a disturbance in the serotonin metabolism of the central nervous system may be of pathogenetic importance in congenital generalized lipodystrophy.
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PMID:Congenital generalized lipodystrophy and experimental lipoatrophic diabetes in rabbits treated successfully with fenfluramine. 57 33

Congenital generalized lipodystrophy is considered to be a diencephalic syndrome with disturbance of hypothalamic transmitters. After puberty and arrest of growth the patients develop a serious untreatable diabetes mellitus. One of our patients, a girl 15 years of age, developed a lipodystrophic diabetes with fasting blood glucose levels above 300 mg/100 ml, increased serum insulin with insulin resistance, and hyperlipidaemia. Daily administration of fenfluramine gave a dramatic improvement. The voracious hunger and profuse perspiration were reduced, the patient's serum lipids became normal, her blood glucose fell, and her sensitivity to exogenous insulin increased. A normalization of the urinary excretion of the serotonin metabolite, 5-OH-indole acetic acid, was observed.
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PMID:Lipodystrophic diabetes treated with fenfluramine. 61 40

Insulin, a primary metabolic hormone, plays a dominant role in the regulation of food intake. An increase in the level of circulating insulin produced by its prandial release from endogenous stores is associated with the state of satiety. On the other hand, an increase in the insulin level produced by its exogenous administration, as well as by its excessive and prolonged release in certain pathological states or during the period of nocturnal overeating, paradoxically gives rise to the sensation of hunger. This differential effect of endogenous and exogenous insulin is analyzed in view of experimental and clinical evidence concerning the principal mechanisms in the regulation of food intake. These include the interrelation of central and peripheral glucosensitive systems, the involvement of the enteroinsular axis, and the effects on these regulatory mechanisms of the physiological state produced by changes in circulating insulin levels. The essential role of the vagus nerve in mediating the hunger and satiety induced by the lack of excess of glucose for cellular oxidation places the short-term glucostatic control in the periphery where the insulin is primarily acting. A unifying hypothesis concerning the role of insulin in the regulation of good intake is proposed and its clinical implications suggested.
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PMID:The role of insulin in the glucostatic control of food intake. 82 7

In addition to established gastrointestinal hormones--secretin, cholecystokinin-pancreozymin (CCK-PZ), gastrin, and glucagon---some 30 polypeptides with gastrointestinal actions can be listed. New aspects of these substances include the following: Gastrin and vasoactive intestinal peptide (VIP) can be also encountered in the central nervous system and may act as transmitters. CCK-PZ-serum concentrations are found markedly elevated in patients with exocrine pancreatic insufficiency; this may provide the opportunity to establish a realtively simple screening test. Moreover, there is evidence that serum-CCK-PZ levels serve as satiety signal. Secretin secretion is said to be enhanced in hunger and then to act as a lipolytic hormone. In addition to enteroglucagon, a gastrintestinal peptide identical to pancreatic glucagon has been detected. Gastric inhibitory polypeptide (GIP) inhibits gastric secretion and motility (enterogastrone activity) and together with glucose it stimulates insulin release (incretin activity). Motilin increases lower esophageal sphincter pressure, enhances gastric pepsin secretion and slows down gastric evacuation. Serum levels of pancreatic polypeptide may be found elevated as a diagnostic index in patients with endocrine peptide tumors of the pancreas. Recently, the potential importance of local (paracrine) actions of gastrointestinal polypeptides has been amphasized. Predominantly paracrine activity is exhibited by some prototype hormones, e.g. somatostatin, substance P, bombesian, and the non-polypeptide compounds, prostaglandins.
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PMID:[New views on gastrointestinal hormones]. 85 99

Karyometric measurements in rats which for 30 days had received a glucose diet or a glucose diet supplemented with thiamine showed the following decrease in nuclear size in contrast to no treated controls. (see article) In both experimental groups there was a 30% loss of weight during the course of the experiment. The different decreases in nuclear volume in the examined organs cannot be explained only by a relative state of hunger. The very large decrease in activity in the fasciculated zone of the adrenal cortex is explained as an adaptation mechanism favouring glucose oxidation by insulin, and the relative increase in activity in the adrenal medulla as an adaptation mechanism to accomplish an elevated lipolysis.
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PMID:[Karyometric studies of the pancreas and adrenal glands of the albino-rat fed an unbalanced glucose diet or a glucose diet supplemented with thiamine]. 109 41

The effect of insulin injection on transmission of neural activity within the olfactory system of the anesthetized male rat was investigated at the single unit level. It was found that insulin changed the response to odors of approximately 27% of olfactory bulb units and 21% of amygdala units tested. Many of the changes were in the direction of an increase in response magnitude, but there were some reversals in response direction and other complex changes. There was no evidence of a selective facilitation of responses to food odor as compared to non-food odors. Control observations of the response of thalamic somatosensory units to tactual stimulation showed no effects of insulin. These results suggest that hypothalamic hunger mechanisms may normally interact with olfactory mechanisms to augment and otherwise change the response of some olfactory system units to various odors.
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PMID:Effects of insulin injection on responses of olfactory bulb and amygdala single units to odors. 118 87

A protein-sparing modified fast (PSMF), which is a total fast modified by the intake of 1.2-1.4 gm. protein per kilogram ideal body weight (IBW), fluids ad libitum, and vitamin and mineral supplementation, allows effective control of carbohydrate metabolism and hunger. It reduces serum glucose and insulin concentrations in obese diabetic patients and increases free fatty acid and ketone body concentrations; ketonuria appears within 24-72 hours. When this fast was applied to seven obese adult-onset diabetics who were receiving 30-100 units of insulin per day, insulin could be discontinued after 0-19 days (mean, 6.5). In the three patients who had extensive nitrogen-balance studies, balance could be maintained chronically by 1.3 gm. protein per kilogram IBW, despite the gross caloric inadequacy of the diet. The PSMF was tolerated well in an outpatient setting after the initial insulin-withdrawal phase had occurred in the hospital. Significant improvements in blood pressure, lipid abnormalities, parameters of carbohydrate metabolism, and cardiorespiratory, symptoms were associated with weight loss and/or the PSMF. For diabetics with some endogenous insulin reserve, the PSMF offers significant advantages for weight reduction, including preservation of lean body mass (as reflected in nitrogen balance) and withdrawal of exogenous insulin.
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PMID:Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast. 127 1

Sodium excretion and the blood levels of aldosterone, renin, atrial natriuretic peptide (ANP), and insulin were investigated in 9 women with obesity of alimentary-constitutional type during hunger therapy and resumed nutrition. It has been assumed that restricted sodium excretion with the kidneys during fasting is mainly caused by activation of the renin-angiotensin-aldosterone system, with ANP contributing to it, insulin not playing the major role in this process.
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PMID:[Hormonal regulation of sodium excretion by the kidneys during hunger therapy of obese patients]. 138 80


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