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)

HMG CoA reductase, which catalyzes the reaction, HMG CoA + 2 NADAPH2 leads to mevalonate + CoA-SH + 2 NADP, is considered to be the rate-limiting enzyme on cholesterol biosynthetic pathway. Since a degree in activity of this enzyme is almost proportional to the rate of cholesterol synthesis from acetate, elucidation of factors that regulate reductase activity would provide insight into the control mechanisms on the cholesterol biosynthesis. In the present study, attempts were made to establish standard assay conditions of HMG CoA reductase activiy, and to qualify the factors affecting the activity of the enzyme. The results obtained were as follows: (1) As standard assay conditions of HMG CoA reductase activity, 85, muM were chosen for substrate concentration, 25-80 mug for microsomal enzyme protein, and 20 min for incubation time in a final volume of 0.1 ml. (2) HMG CoA reductase activity of rat liver microsomes was exhibited diurnal variation. The level of reductase activity at night was 4 fold higher than that of at daytime. (3) Either ATP or insulin administration stimulated hepatic HMG CoA reductase activity. But, cyclic AMP had no effect on reductase activity. The stimulatory effect of ATP or insulin on reductase activity was inhibited by a preadministration of glucagon. These results suggested that an interplay of hormone might regulate reductase activity and consequently cholesterol biosynthesis. (4) HMG CoA reductase activity was increased by preincubation of microsomes with cytosol. Presence of ATP or Mg++ intensified this effect. When digested by trypsin or degenerated by heat treatment, cytosol lost the stimulating activity. These results suggested as existence of protein factors in cytosol, which might modulate the enzyme interconversion from inactive to active forms.
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PMID:[Studies on the regulatory factors of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) activity]. 18 33

1. The subcellular distribution of adenine nucleotides, acetyl-CoA, CoA, glutamate, 2-oxoglutarate, malate, oxaloacetate, pyruvate, phosphoenolpyruvate, 3-phosphoglycerate, glucose 6-phosphate, aspartate and citrate was studied in isolated hepatocytes in the absence and presence of glucagon by using a modified digitonin procedure for cell fractionation. 2. In the absence of glucagon, the cytosol contains about two-thirds of cellular ATP, some 40-50% of ADP, acetyl-CoA, citrate and phosphoenolpyruvate, more than 75% of total 2-oxoglutarate, glutamate, malate, oxaloacetate, pyruvate, 3-phosphoglycerate and aspartate, and all of glucose 6-phosphate. 3. In the presence of glucagon the cytosolic space shows an increase in the content of malate, phosphoenolpyruvate and 3-phosphoglycerate by more than 60%, and those of aspartate and glucose 6-phosphate rise by about 25%. Other metabolites remain unchanged. After glucagon treatment, cytosolic pyruvate is decreased by 37%, whereas glutamate and 2-oxoglutarate decrease by 70%. The [NAD(+)]/[NADH] ratios calculated from the cytosolic concentrations of the reactants of lactate dehydrogenase and malate dehydrogenase were the same. Glucagon shifts this ratio and also that of the [NADP(+)]/[NADPH] couple towards a more reduced state. 4. In the mitochondrial space glucagon causes an increase in the acetyl-CoA and ATP contents by 25%, and an increase in [phosphoenolpyruvate] by 50%. Other metabolites are not changed by glucagon. Oxaloacetate in the matrix is only slightly decreased after glucagon, yet glutamate and 2-oxoglutarate fall to about 25% of the respective control values. The [NAD(+)]/[NADH] ratios as calculated from the [3-hydroxybutyrate]/[acetoacetate] ratio and from the matrix [malate]/[oxaloacetate] couple are lowered by glucagon, yet in the latter case the values are about tenfold higher than in the former. 5. Glucagon and oleate stimulate gluconeogenesis from lactate to nearly the same extent. Oleate, however, does not produce the changes in cellular 2-oxoglutarate and glutamate as observed with glucagon. 6. The changes of the subcellular metabolite distribution after glucagon are compatible with the proposal that the stimulation of gluconeogenesis results from as yet unknown action(s) of the hormone at the mitochondrial level in concert with its established effects on proteolysis and lipolysis.
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PMID:Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate. 19 59

The effect of tolbutamide on pyridine nucleotides and insulin secretion stimulated by aminophylline, 3,5-AMP-dibutyrate or glucagon was studied in pancreatic islets of rats previously treated with 6-aminonicotinamide (6-AN), an inhibitor of pyridine nucleotide synthesis. After being incubated for 60 min in a Krebs-Ringer-Bicarbonate-Buffer in the absence of glucose, pancreatic islets of rats i.p. injected with 35 mg/kg of 6-AN 6 hrs before pancreas removal contained about 30% less NADP and NADPH than did islets of control rats. No changes of NDA or NADH were observed in islets of 6-AN-treated animals. Addition of 16.5 mM glucose led to an increase of NADH, NADPH and a decrease of NADP in islets of both groups of animals; NAD levels remained unchanged. In vitro addition of tolbutamide to islets of control rats did not affect the levels of NADPH or NADP in the presence of 5.5 mM glucose. When 16.5 mM glucose were present, a decrease of NADPH and an increase of NADP was obvious. No effect of tolbutamide on insular NADPH or NADP was observed in islets of rats previously treated with 6-AN be it in the presence of 5.5 or 16.5 mM glucose. In islets of 6-AN-treated rats insulin release in response to aminophylline or 3,5-AMP-dibutyrate in the presence of 5.5 mM glucose was significantly depressed, when compared to islets of untreated controls. Addition of tolbutamide increased insulin release due to aminophylline, 3,5-AMP-dibutyrate or glucagon islets of controls. Tolbutamide alone was without effect. In islets of 6-AN-treated rats aminophylline, 3,5-AMP-dibutyrate or glucagon stimulated insulin release only when tolbutamide was present. Our data suggest that there is no direct interference of tolbutamide with pyridine nucleotides of pancreatic islets, and that tolbutamide increases the secretory response of the beta-cell to aminophylline, 3,5-AMP-dibutyrate or glucagon when insulin release due to these agents is inhibited during decrease of insular NADP and NADPH, caused by 6-AN.
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PMID:Effect of tolbutamide on aminophylline-, 3,5-AMP-dibutyrate- or glucagon-induced insulin release from pancreatic islets after impairment of pyridine nucleotide metabolism caused by 6-aminonicotinamide (6-AN). 24 43

The effects of various nucleosides and nucleotides upon glucagon secretion from the isolated perfused rat pancreas were studied. Increasing glucagon secretion was found with increasing concentrations of exogenous cyclic AMP (2 X 10(-4) M, 2 X 10(-3) M and 1 X 10(-2) M). Stimulation of alpha cell secretion was also found with 2 X 10(-3) M 2'AMP, 3'AMP, 5'AMP, ADP, Adenosine, NADP, and NADPH. One X 10(-3) M cyclic GMP elicited significant glucagon secretion. The pattern of glucagon release was similar in all cases with peak secretion occurring during the 30- to 90-s time period following initiation of the stimulus. No significant increase of glucagon secretion was found in response to ATP, guanosine, 2'GMP, 3'GMP, 5'GMP, GTP, xanthosine, inosine, adenine, xanthine, thymidine, cytidine, ribose, nicotinamide, and uric acid. On the basis of the above results, the structural requirement for stimulation of glucagon secretion appears to be adenine linked to ribose, with phosphate groups being unnecessary. The conclusion of this study is that a new class of compounds capable of stimulating glucagon secretion has been identified, and important questions are thus raised about the mechanism of the action of exogenous cyclic AMP.
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PMID:Nucleotide and nucleoside stimulation of glucagon secretion. 110 53

Clofibrate induces hypertrophy and hyperplasia and marked changes in the activities of various enzymes in rat liver. We examined the effects of treatment of rats with clofibrate on enzyme induction and on rates of metabolic flux in hepatocytes isolated from the periportal and perivenous zones of the liver. Clofibrate induced the activities of carnitine acetyltransferase (90-fold), carnitine palmitoyltransferase (3-fold) and NADP-linked malic enzyme (3-fold) to the same level in periportal as in perivenous hepatocytes, suggesting that these enzymes were induced uniformly throughout the liver acinus. Increased rates of palmitate metabolism and ketogenesis after clofibrate treatment were associated with: a more oxidised mitochondrial redox state; diminished responsiveness to glucagon and loss of periportal/perivenous zonation. Despite the marked liver enlargement and hyperplasia caused by clofibrate, the normal periportal/perivenous zonation of alanine aminotransferase and gluconeogenesis was preserved in livers of clofibrate-treated rats, indicating that clofibrate-induced hyperplasia does not disrupt the normal acinar zonation of these metabolic functions.
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PMID:Clofibrate induces carnitine acyltransferases in periportal and perivenous zones of rat liver and does not disturb the acinar zonation of gluconeogenesis. 277 85

L-Lysine-2-oxoglutarate reductase (EC 1.5.1.8, NADP) in the liver of adult rats increased 4-5 times when the animals were treated with alloxan. In diabetic rats injection of insulin or adrenalectomy prevented the increase in enzyme activity. The activity of the similar enzyme in kidney was not changed by these treatments. The enzyme activity in primary cultured adult rat hepatocytes was also induced by addition of dexamethasone and glucagon together, and glucagon could be replaced by dibutyryl cyclic AMP. Insulin inhibited the induction. The hormonal induction was also inhibited by actinomycin D and by cycloheximide. During development of rats, fetal liver showed very low activity, but the activity appeared on day 1 after birth and then increased rapidly, reaching the adult level by day 5. The activity of the kidney enzyme increased more slowly and reached adult level 1 month after birth. Intra-uterine injection of glucagon caused precocious induction of the liver enzyme in fetuses. These results indicate that the activity of L-lysine-2-oxoglutarate reductase in the adult liver and in part in neonatal liver also, in controlled by both glucagon and glucocorticoid.
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PMID:Induction of L-lysine-2-oxoglutarate reductase by glucagon and glucocorticoid in developing and adult rats: in vivo and in vitro studies. 701 89

Oxidative decarboxylation is the first irreversible step in the degradation of leucine. The effect of streptozotocin diabetes on this reaction was studied in cell-free rat liver preparations, using [1-14C]alpha-ketoisocaproate as substrate. Diabetes increased the branched-chain ketoacid dehydrogenase (BCKD) activity (per g liver or per mg protein) of homogenates, but the ratios of homogenate BCKD activity to other mitochondrial markers remained unchanged. A cytosolic branched-chain ketoacid decarboxylase activity (15-22% of homogenate activity), which did not require NAD, CoA, or NADP, was also increased in diabetics. Insulin treatment of diabetics normalized enzyme activity in all fractions. The apparent Km of BCKD in homogenates was 43-45 microM; diabetes increased the apparent Vmax from 165 nmol x min-1 x g tissue-1 to 260 nmol x min-1 x g-1. In contrast, the Km for cytosolic alpha-ketoisocaproate decarboxylation was 270 microM in controls, and diabetes resulted in both a lower Km (210 microM) and a higher Vmax. Adrenalectomy did not affect activity in homogenates from controls, but partially reversed the diabetes-associated increase. Glucagon pretreatment of controls did not affect activity. In summary, distinct mitochondrial and cytosolic enzymes decarboxylate alpha-ketoisocaproate in liver. The increased hepatic capacity of diabetic rats to degrade the carbon skeleton of leucine is attributed mainly to a relative increase in mitochondrial mass.
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PMID:Effects of diabetes on oxidative decarboxylation of branched-chain keto acids. 743 56

1. The concentration and oxidoreduction state of the liver nicotinamide nucleotides of rats subjected to a number of hormonal treatments have been measured. 2. Adrenalectomy decreases the NADP(+) content by 80% but has little effect on NAD(+), NADH or NADPH. High doses of cortisone produce similar changes, but more physiological doses (5mug. daily) tend to increase the NADP(+) content. 3. Glucagon treatment of normal rats lowered the NADH and NADP(+) concentrations but did not affect the total amounts present. Growth hormone increased the concentrations and total amounts of NAD(+) and NADH but significantly decreased the concentrations and total amounts of NADP(+) and NADPH. 4. Measurements have been made of a number of enzymes in the livers of adrenalectomized and glucagon-treated rats that could affect the oxidoreduction state of NADP. The activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase are not affected by adrenalectomy or treatment with cortisone or glucagon. Nor does adrenalectomy affect the activity of NADPH-cytochrome c oxidoreductase or NADPH-glutathione oxidoreductase. The hepatic content of glutathione is, however, decreased 50% by adrenalectomy. 5. Measurements of the oxidation of [1-(14)C]glucose and [6-(14)C]glucose by liver slices from adrenalectomized rats showed that glucose oxidation was substantially normal, although phenazine methosulphate caused a smaller stimulation of the oxidation of C-1 of [1-(14)C]glucose in slices from the livers of adrenalectomized rats than it did with slices from controls. The hepatic synthesis of lipids from [1-(14)C]glucose was marginally increased in adrenalectomized rats. 6. The additional NADP(+) found when liver is extracted with 0.02n-sulphuric acid-0.1m-sodium sulphate is less affected than the NADP(+) extracted with 0.1n-hydrochloric acid in adrenalectomized or glucagon-treated rats. Hooded Norway rats appear to have less of this extra form of NADP(+) than albino rats. 7. An attempt has been made to correlate the observed changes in the nicotinamide nucleotides with metabolic patterns prevailing in different hormonal conditions.
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PMID:THE EFFECT OF DIFFERENT HORMONAL CONDITIONS ON THE CONCENTRATION AND OXIDOREDUCTION STATE OF THE NICOTINAMIDE NUCLEOTIDES OF RAT LIVER. 1433 53