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)

Hormonal status was evaluated in TCDD-treated rats and in pair-fed and ad libitum-fed controls in order to separate hormonal changes resulting from the toxic insult of TCDD from those arising from progressive feed deprivation as it occurs in pair-fed controls. TCDD-treated rats received either a usually non-lethal (25 micrograms/kg) or a usually lethal (125 micrograms/kg) dose of TCDD whereas pair-fed and ad libitum-fed controls were given vehicle alone. Animals were terminated at predetermined time intervals and several hormones measured in serum or plasma. In addition, the morphology of the thyroid, pancreas, and pituitary was also examined. In both dosage groups, TCDD-treatment had the following effects: decreased TT4, FT4, insulin, and glucagon; mixed effects upon TT3, FT3, TSH, and GH. Pair-feeding to the non-lethal dose of TCDD had no effect on any of the hormones measured. Pair-feeding to the lethal dose of TCDD had the the following effects: slightly decreased TT4, FT4, TT3, TSH, and insulin; no effect on FT3 and glucagon. It is concluded that the endocrine status of TCDD-treated rats was different from that of pair-fed rats suggesting that some hormonal changes represent responses to an insult other than that due to starvation stress alone. A differential response between TCDD-treated and pair-fed rats was also observable morphologically in the corresponding endocrine glands indicating the importance of this additional control for morphologic observations in instances when reduced feed intake and body weight loss are prominent features of toxicity.
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PMID:Some endocrine and morphological aspects of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 305 89

1. Rates of lipolysis were measured at different concentrations of glucagon in adipocytes prepared from parametrial adipose tissue of fed or starved rats in different reproductive states. All experiments were performed in the presence of a high concentration of adenosine deaminase (1 unit/ml). 2. Maximal rates of lipolysis (elicited by 25 nM-glucagon in each instance) were higher in adipocytes from peak-lactating rats than those from pregnant animals in both the fed and starved states. 3. Of adipocytes from fed animals, those from peak-lactating rats were the most sensitive to glucagon, whereas those from late-pregnant and early-lactating rats were 1-2 orders of magnitude less sensitive. 4. Adipocytes from 24 h-starved rats showed a much smaller stimulation of lipolysis by glucagon, making the assessment of sensitivity difficult. Therefore, rates of lipolysis were also measured in the presence of a maximally anti-lipolytic dose of insulin. The presence of insulin did not alter the relative sensitivities to glucagon of adipocytes from fed animals in different reproductive states, although all dose-response curves were shifted to the right. When lipolysis in adipocytes from starved animals was measured in the presence of insulin, it became evident that starvation for 24 h markedly increased the sensitivity of adipocytes from late-pregnant rats to glucagon, but did not affect that of cells from animals in the other reproductive states. 5. It is concluded that the large changes in sensitivity to glucagon that occurred during the reproductive cycle may enable the modulation of adipose-tissue lipolysis in vivo to satisfy the different metabolic requirements of the animal in the transition from pregnancy to peak lactation.
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PMID:Changes in the sensitivity to glucagon of lipolysis in adipocytes from pregnant and lactating rats. 305 15

Phosphorus is the sixth most abundant element in the body after oxygen, hydrogen, carbon, nitrogen, and calcium. It comprises about 1% of the total body weight of humans. Eighty-five percent of it is stored in the bone in the form of hydroxyapatite crystal; 14% is in the soft tissues in the form of energy-storing bonds with nucleotides (ATP, GTP), nucleic acids in chromosomes and ribosomes, 2,3-DPG in the red blood cells, and phospholipids in the cells' membranes. Less than 1% is in the extracellular fluids. Phosphate balance is maintained by multiple systems. The gut is responsible for the absorption of two thirds of the 4-30 mg/kg/day of phosphate intake. Absorption sites are all along the gut; in humans the most active site is the jejunum. The kidney filters 90% of the plasma phosphate and reabsorbs it in the tubuli. In states of hypophosphatemia the kidney can reabsorb the filtered phosphates very efficiently, reducing the amount excreted in the urine virtually to zero. The healthy kidney can excrete high loads of phosphate and rid the body of phosphate overload. Through the vitamin D-PTH axis the endocrine system regulates the phosphate balance by influencing the kidney, gut, and bone. Other hormones, including thyroid, insulin, glucagon, glucocorticosteroid, and thyrocalcitonin, play a lesser role in regulation of phosphate metabolism. Because of the complex control of phosphate homeostasis, various clinical conditions may lead to hypophosphatemia. These include nutritional repletion, gastrointestinal malabsorption, use of phosphate binders, starvation, diabetes mellitus, and increased urinary losses due to tubular dysfunction. The clinical picture of phosphate depletion is manifested in different organs and is due mainly to the fall in intracellular levels of ATP and decreased availability of oxygen to the tissues, secondary to 2,3-DPG depletion. The various manifestations of phosphate depletion are listed in Table 2. The treatment of hypophosphatemia consists of administering enteral or parenteral phosphate salts. An important aspect of dealing with the potentially serious effects of phosphate depletion is to prevent the depletion from happening in the first place. Hyperphosphatemia can occur in renal failure, hemolysis, tumor lysis syndrome, and rhabdomyolysis. The treatment of hyperphosphatemia usually consists of fluid administration (in the absence of kidney failure). In chronic hyperphosphatemia, phosphate binders such as aluminum and magnesium salts can reduce the phosphate load. The use of these phosphate binders is limited by their potential side effects.
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PMID:Consequences of phosphate imbalance. 306 Jan 61

Chicks of king penguin (Aptenodytes patagonica), while only 3-4 months old, tolerate 4-6 months of fasting when they are abandoned by their parents during the subantarctic winter. The body mass of nine chicks, which were followed during this natural winter fast, was 13.1 kg at capture and 3.4 kg after 150 days of fasting, a 74% decrease. The longer phase II (129 days) was marked by lipid mobilization and protein sparing, as indicated by a continuous increase in plasma levels of free fatty acids, glycerol, and beta-hydroxybutyrate, whereas plasma alanine, uric acid, and urea remained stable at low values. In phase III, by contrast, plasma concentrations of lipid-derived metabolites decreased, while plasma alanine, uric acid, and urea increased markedly, indicating an increase in protein utilization. Plasma insulin concentration did not significantly change during either phase II or phase III. Plasma glucagon remained constant during phase II and at the beginning of phase III but increased 2.6 times afterward. Plasma corticosterone increased only slightly during the first 4 months of the fast but reached very high values at the end of phase II and the beginning of phase III (4.7 times basal values); moreover, it further increased 3.1 times before phase III was stopped. Altogether, these data accord with the idea that the outstanding resistance of king penguin chicks to starvation is due to the ability to extensively prolong the situation of protein sparing, which seems to require the maintenance of low plasma concentrations of corticosterone and insulin for up to 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma hormone levels in relation to lipid and protein metabolism during prolonged fasting in king penguin chicks. 306 Mar 95

The existence of a co-ordinated response to stress of a variety of causes has clearly been established. Basically, this consists of an elevation in energy expenditure and an increased breakdown of skeletal muscle protein. In addition, glucose level in the plasma increases as a result of increased synthesis and decreased uptake of glucose into cells. Release of fatty acid into the plasma is also increased, and an elevation in the proportion of energy derived from oxidation of fatty acids is observed. This response is qualitatively very different from that seen in simple starvation, where a progressive reduction in energy expenditure and a reduction in the synthesis of glucose allows fat to become the major energy-producing substrate and also allows sparing of body protein stores. The mechanisms responsible for this altered pattern of metabolism are probably primarily hormonal in nature, with adrenaline, cortisol and glucagon being the major catabolic stimulants. Some evidence exists, however, for alteration in intracellular pathway metabolism. Within the past decade a new class of mediators of the stress response, the cytokines, has been recognized. These substances are protein products of circulating monocytes and the way in which they integrate into the control of the stress response has not been completely elucidated. At present there is evidence that they can stimulate production of catabolic hormones, and also they may well have direct effects in enhancing protein catabolism in muscle. At present the main method for modification of the stress response remains the provision of energy and amino acid, either intravenously or enterally. In the present state of our knowledge, 30-40 kcal kg-1 day-1 would appear to be adequate for most patients, with half provided as fat. Amino acids 3 g kg-1 day-1 will provide adequate nitrogen. It must be said, however, that the most effective method of modifying the stress response is removal of the source of stress by surgery, antibiotics or other primary therapy.
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PMID:The metabolic and nutritional effects of injury and sepsis. 307 81

Induction of cytosolic aspartate aminotransferase (cAspAT) was observed in rat liver on administration of a high-protein diet, or glucagon and during fasting. The enzyme activity in the liver of rats given 80% protein diet or glucagon injection during starvation increased to 2- to 2.4-fold that in the liver of rats maintained on 20% protein diet, with about 2-fold increases in the levels of hybridizable cAspAT mRNA, measured by blot analysis using the cloned rat cAspAT cDNA as a probe. No increase in the enzyme was detected in kidney, heart, brain, or skeletal muscle. The activity of mitochondrial aspartate aminotransferase (mAspAT) did not increase. Induction of cAspAT was observed when glucose metabolism tended toward gluconeogenesis. The physiological function of the induction of cAspAT is considered to be to increase the supply of oxaloacetate as a substrate for cytosolic phosphoenolpyruvate carboxykinase (PEPCK) [EC 4.1.1.32] for gluconeogenesis.
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PMID:Rat cytosolic aspartate aminotransferase: regulation of its mRNA and contribution to gluconeogenesis. 318 50

Chicks of the king penguin (Aptenodytes patagonica) can tolerate a fast of 4-6 months during the subantarctic winter. The aim of this work was to study their initial response to food deprivation. Nine chicks were starved for 18 days. Two phases of starvation were defined according to changes in the specific daily loss in body mass: it decreased by 92% in phase I (6.6 +/- 0.3 days) and remained steady and low in phase II. Phase I was marked by a large decline in protein utilization, indicated by decreases in plasma levels of alanine (58%), uric acid (89%) and urea (76%) together with a decrease in circulating corticosterone (60%) and thyroxine (75%). In phase I, plasma insulin concentration decreased (61%) in some birds, but did not change in others; plasma pancreatic glucagon was stable whereas gut-glucagon decreased by 75%. Free fatty acids and beta-hydroxybutyrate concentrations gradually rose during the fast to 5 to 6 times pre-fast levels. Glycemia remained unchanged. Phase II was characterized by no change in plasma concentrations of protein-derived metabolites and by no or little change in circulating hormone levels. From comparison with previous data, we conclude that there are similar early adjustments to food deprivation in king penguin chick, rat and man: (1) a decrease in resting metabolic rate, (2) a decrease in protein utilization, and (3) mobilization of fat stores. The key adaptations to long-term fasting in these species are therefore effectiveness in protein sparing and ability to prolong this situation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early changes in plasma hormones and metabolites during fasting in king penguin chicks. 322 Sep 86

1. A permeabilized isolated rat liver cell preparation was developed to achieve selective permeabilization of the cell membrane to metabolites and to allow the assay of mitochondrial overt carnitine palmitoyltransferase (CPT I) activity in situ. By performing the digitonin-induced permeabilization in the presence of fluoride and bivalent-metal-cation sequestrants, it was possible to demonstrate that the activity of other enzymes, which are regulated by reversible phosphorylation, was preserved during the procedure and subsequent washing of cells before assay. 2. CPT activity at a sub-optimal palmitoyl-CoA concentration was almost totally (approximately 90%) inhibited by malonyl-CoA, indicating that mitochondrial CPT I was largely measured in this preparation. 3. The palmitoyl-CoA-saturation and malonyl-CoA-inhibition curves for CPT activity in permeabilized cells were very similar to those obtained previously for the enzyme in isolated liver mitochondria. Moreover, starvation and diabetes had the same effects on enzyme activity, affinity for palmitoyl-CoA and malonyl-CoA sensitivity of CPT I in isolated cells as found in isolated mitochondria. These physiologically induced changes persisted through the cell preparation and incubation period. 4. Neither incubation of cells with glucagon or insulin nor incubation with pyruvate and lactate before permeabilization resulted in alterations of these parameters of CPT I in isolated cells. 5. The results are discussed in relation to the temporal relationships of changes in the activity and properties of CPT I in vivo in relation to the effects of insulin and glucagon on fatty acid metabolism in vivo.
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PMID:Use of a selectively permeabilized isolated rat hepatocyte preparation to study changes in the properties of overt carnitine palmitoyltransferase activity in situ. 328 53

The continuous turnover of intracellular protein and other macromolecules is a basic cellular process that serves, among other functions, to regulate cytoplasmic content and provide amino acids for ongoing oxidative and biosynthetic reactions during nutrient deprivation. The intensity of breakdown and pattern of regulation, though, vary widely among cells. Rat hepatocytes, for example, exhibit high absolute rates of proteolysis and regulatory effects that diminish during starvation, while corresponding responses in skeletal and cardiac muscle move in the opposite direction. It is also becoming apparent that effects of insulin and other acute regulatory agents on muscle breakdown are limited to nonmyofibrillar components. The latter may be sequestered and degraded within autophagic vacuoles, whereas myofibrillar proteins require an initial attack by calcium-dependent proteases in the cytosol. By contrast, most if not all of the breakdown of resident (long-lived) proteins as well as RNA in the hepatocyte can be explained by lysosomal mechanisms. The uptake of cytoplasmic components by lysosomes can be divided into two major categories, macroautophagy and micro- or basal autophagy. The first is induced by amino acid or insulin/serum deprivation. In the hepatocyte, amino acids alone can regulate this process almost instantaneously over two thirds of the full range of proteolysis, 4.5% to 1.5% per hour. Glucagon, cyclic AMP, and beta-agonists also stimulate macroautophagy in hepatocytes but have opposite effects in skeletal and cardiac myocytes. Basal autophagy differs from the macro type in that the cytoplasmic "bite" is smaller and sequestration is not acutely regulated. It is, however, adaptively decreased during starvation in parallel with absolute rates of basal turnover. Since endoplasmic reticulum comprises an appreciable fraction of the vacuolar content, volume sequestration would be compatible with the known heterogeneity of individual protein turnover if some proteins (or altered proteins) selectively bind to membranes. The amino acid control of macroautophagy in the hepatocyte is accomplished by a small group of direct inhibitors (Leu, Tyr/Phe, Gln, Pro, Met, Trp, and His) and the permissive effect of alanine whereas only leucine is involved in myocytes and adipocytes. Of unusual interest is the fact that the inhibitory amino acid group alone evokes responses in perfused livers that are identical to those of a complete plasma mixture at 0.5 and 4 times normal plasma levels but loses effectiveness almost completely at normal concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intracellular protein catabolism and its control during nutrient deprivation and supply. 330 Jul 46

In winter, hibernating mammals enter a long phase of lethargy which is characterized by low body temperature, depressed metabolism and minimal release of metabolic substrates from endogenous fuel stores. Periodically, they spontaneously warm themselves to regain the euthermic state. These arousals are, by contrast, times of high release and consumption of endogenous substrates. Insulin and glucagon may contribute to the control of both contrasting metabolic periods. The secretion and metabolic effects of these two hormones were investigated in two hibernators: the hedgehog (Erinaceus europaeus) and the edible dormouse (Glis glis). During lethargy, blood glucose, insulin and glucagon concentrations were low. In vivo and in vitro studies showed that the secretion of both hormones was markedly depressed by low temperatures. Insulin secretion was not stimulated by glucose, although glucagon secretion remained reactive to arginine. Blood glucose was not regulated by insulin but pharmacological doses of glucagon increased blood glucose concentrations. The tissues were found to be highly insulin-resistant, preventing the fall of blood glucose and consequently limiting the depletion of glucidic substrates during the long periods of starvation. During arousal, blood glucose, insulin and glucagon levels increased at the end of rewarming while glucose turnover gradually increased above a body temperature of 15 degrees C. The effects of glucagon and insulin on glucose metabolism increased markedly beyond this stage. Thus the metabolic effect of both hormones are temperature-dependent. Insulin and glucagon allow an increase in glucose availability for the active metabolic processes which occur during arousal.
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PMID:[Regulation of endocrine pancreas secretions (insulin and glucagon) during the periodic lethargy-waking cycle of the hibernating mammal]. 330 41


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