Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:034761 (insulin)
 211,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An assay of lipolytic activity in human adipose tissue is described, in which native homogenates of the adipose tissue yield the enzyme, as well as the triglyceride substrate, and the emulsifying phospholipids. The lipolytic activity in the presence of serum is characterized mainly as lipoprotein lipase activity by a pH-optimum of 8.0, by the fact that serum is necessary for full activity, and that it is inhibited by 1 M NaCl and by protamine. At serum concentrations of higher than 50% a marked inhibition of the lipolysis is observed. Noradrenaline, insulin, and heparin have no effect on the serum-stimulated lipolytic activity.
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PMID:Assay and characterization of serum-stimulated lipolytic activity in homogenates of human adipose tissue. 1 66

The intraaxonal transport of noradrenaline and tyrosine hydroxylase was studied in the sciatic nerves of diabetic, obese and appropriate control mice. Noradrenaline and tyrosine hydroxylase accumulated proximal to a constriction applied to the nerves. Noradrenaline concentration in the non-constricted sciatic nerves did not differ significantly in nondiabetic and diabetic mice (0.67 +/- 0.04 and 0.58 +/- 0.01 ng/cm respectively); in obese mice and lean littermates the noradrenaline concentration was 0.47 +/- 0.05 ng/cm and 0.46 +/- 0.01 ng/cm. After nine hours of constriction the concentration of noradrenaline increased in the axons of nondiabetic (1.15 +/- 0.06 ng/cm), in obese (0.90 +/- 0.08 ng/cm) and lean mice (1.10 +/- 0.07 ng/cm) but remained low (0.68 +/- 0.07 ng/cm) in diabetic mice.--Administration of insulin (10 U/kg/day) to diabetic mutants completely reversed the decrease in NA accumulation. NA accumulated only in the nerve segment proximal (1 cm) to a constriction and was transported distally at an apparent velocity of 0.75 mm/hr in control axons. The difference of NA accumulation between diabetic and nondiabetic control indicate a reduced rate of axoplasmic flow in the noradrenergic axons of diabetic animals.
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PMID:Axoplasmic transport of noradrenaline in the sciatic nerves of spontaneously diabetic mice. 3 48

In fat cells isolated from the parametrial adipose tissue of rats, the addition of purified adenosine deaminase increased lipolysis and cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation. Adenosine deaminase markedly potentiated cyclic AMP accumulation due to norepinephrine. The increase in cyclic AMP due to adenosine deaminase was as rapid as that of theophylline with near maximal effects seen after only a 20-sec incubation. The increases in cyclic AMP due to crystalline adenosine deaminase from intestinal mucosa were seen at concentrations as low as 0.05 mug per ml. Further purification of the crystalline enzyme preparation by Sephadex G-100 chromatography increased both adenosine deaminase activity and cyclic AMP accumulation by fat cells. The effects of adenosine deaminase on fat cell metabolism were reversed by the addition of low concentrations of N6-(phenylisopropyl)adenosine, an analog of adenosine which is not deaminated. The effects of adenosine deaminase on cyclic AMP accumulation were blocked by coformycin which is a potent inhibitor of the enzyme. These findings suggest that deamination of adenosine is responsible for the observed effects of adenosine deaminase preparations. Protein kinase activity of fat cell homogenates was unaffected by adenosine or N6-(phenylisopropyl)adenosine. Norepinephrine-activated adenylate cyclase activity of fat cell ghosts was not inhibited by N6-(phenylisopropyl)adenosine. Adenosine deaminase did not alter basal or norepinephrine-activated adenylate cyclase activity. Cyclic AMP phosphodiesterase activity of fat cell ghosts was also unaffected by adenosine deaminase. Basal and insulin-stimulated glucose oxidation were little affected by adenosine deaminase. However, the addition of adenosine deaminase to fat cells incubated with 1.5 muM norepinephrine abolished the antilipolytic action of insulin and markedly reduced the increase in glucose oxidation due to insulin. These effects were reversed by N6-(phenylisopropyl)adenosine. Phenylisopropyl adenosine did not affect insulin action during a 1-hour incubation. If fat cells were incubated for 2 hours with phenylisopropyl adenosine prior to the addition of insulin for 1 hour there was a marked potentiation of insulin action. The potentiation of insulin action by prior incubation with phenylisopropyl adenosine was not unique as prostaglandin E1, and nicotinic acid had similar effects.
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PMID:Effects of adenosine deaminase on cyclic adenosine monophosphate accumulation, lipolysis, and glucose metabolism of fat cells. 16 37

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release. 17 62

Isolated adipocytes, incubated in the presence of extracellular 32Pi to steady state 32P incorporation into cellular phosphopeptides, were exposed to hormones for 5 min. Epinephrine (10(-6) M) stimulated 32P incorporation into at least 12 major phosphopeptides, distributed in the cytoplasm, endoplasmic reticulum, and plasma membrane. Quantitatively pre-eminent among these were peptides of molecular weight 123,000 and 69,000, each located both in the cytoplasm and endoplasmic reticulum. The effect of epinephrine (10(-7) M) on 32P incorporation into these two peptides was augmented by theophylline (10(-3) M) in a synergistic fashion. Norepinephrine, dibutyryl N6,O2'-dibutyryl adenosine 3':5'-monophosphate, adrenocorticotropic hormone (ACTH) (synthetic 1 to 24 fragment), and glucagon mimicked the effect of epinephrine. Insulin modified adipocyte peptide phosphorylation in two ways. When present as the sole hormone, insulin (100 microunits/ml) consistently and selectively stimulated the 32P incorporation into a peptide of molecular weight 123,000 (endoplasmic reticulum, cytoplasm) without significant alteration in the 32P content of any other major peptide. A second effect of insulin was evident when epinephrine (10(-6) M) was present simultaneously. Insulin significantly inhibited the epinephrine-stimulated phosphorylation of the molecular weight 69,000 (endoplasmic reticulum, cytoplasm) and 26,000 (plasma membrane) peptides. Nevertheless, persistence of insulin-stimulated phosphorylation of the 123,000 peptide in the presence of epinephrine was shown by a 32P content of this peptide that was greater in the presence of both hormones than with either individually. These findings indicate that in intact adipocytes: (a) epinephrine acutely alters the phosphorylation of a large number of adipocyte peptides, partly at least, via activation of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase; (b) insulin opposes several epinephrine-stimulated phosphorylations in a manner consitent with its ability to lower epinephrine-stimulated intracellular cyclic AMP accumulation in adipocytes; and (c) insulin, in addition, exerts a unique stimulatory effect on adipocyte peptide phosphorylation that is independent of its effects on cyclic AMP metabolism and may be medicated by the generation of an as yet undefined intracellular "messenger" unique to insulin.
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PMID:Effects of epinephrine and insulin on phosphopeptide metabolism in adipocytes. 17 55

The regulation of glycogen metabolism in C-6 astrocytoma and C-1300 neuroblastoma cells in culture has been investigated. Two modes of control of glycogen metabolism appear to be operative. The regulation of intracellular glycogen concentrations and the predominant forms of glycogen phosphorylase and glycogen synthase vary with (a) the available energy supply, and (b) altered intracellular concentration of cyclic adenosine 3':5'-monophosphate (cyclic AMP). Both cell lines respond to glucose in the medium; when glucose levels are high, glycogen is synthesized, glycogen phosphorylase a decreases, and glycogen synthase a increases. When glucose in the medium decreases to a critical level, the phosphorylase a increases and glycogen concentrations in the cells decrease in aprallel with the medium glucose. The critical glucose concentration is 2.5 mM for the astrocytoma cells and 4 mM for the neuroblastoma cells. Insulin promotes the conversion of phosphorylase to the b form and synthase to the a form in both cell lines. All of these changes occur without alteration in the intracellular cyclic AMP concentrations. When cyclic AMP concentrations are increased in either cell line, phosphorylase a is increased, synthase a is decreased, and glycogen concentrations decrease. Isobutyl methylxanthine is effective in promoting glycogenolysis in both cell lines. Norepinephrine is effective with the astrocytoma cells, and prostaglandin E1 is effective with the neuroblastoma cells.
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PMID:Regulation of glycogen metabolism in astrocytoma and neuroblastoma cells in culture. 17 53

1. Adrenaline and noradrenaline have been infused into the fetal sheep to produce plasma concentrations comparable to those seen during hypoxia. The effects have been compared with those of isoprenaline and methoxamine and the sensitivity to beta- and alpha-adrenergic antagonists has been followed. 2. Adrenaline caused an alpha-mediated increase in blood glucose that is associated with a fall in plasma insulin concentration. It also caused a beta-mediated increase in plasma lactate, free fatty acid and amino acid concentrations. 3. Noradrenaline was much less effective than adrenaline at eliciting metabolic responses. It had not cause a significant change in plasma glucose concentration, although this was associated with a small increase in plasma insulin concentration. It caused a small rise in the concentration of lactate and free fatty acids in fetal plasma but had no effect on plasma amino acids. 4. The beta- and alpha-adrenergic antagonists propranolol and phentolamine alone were without effect on any of the plasma metabolites or hormones assayed. Isoprenaline increased plasma glucose, lactate, free fatty acid, alanine and insulin concentrations, while methoxamine only increased plasma glucose and lactate, and this was associated with a fall in insulin concentration. 5. The concentration of ACTH in fetal plasma was increased by adrenaline and to a lesser extent by noradrenaline and methoxamine; these were blocked by phentolamine. Isoprenaline also caused a small increase in ACTH. There were no corticosteroid changes associated with the increase in ACTH. 6. The results have been discussed in relation to the adrenergic and pancreatic control of metabolism in the fetal sheep.
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PMID:The metabolic and endocrine effects of circulating catecholamines in fetal sheep. 21 88

Incubation of rat hepatocytes for 3 hours in a sterol-free medium containing 1.5% albumin resulted in efflux of cellular sterol into the medium and an increased activity of 3-hydroxy-3-methylglutaryl CoA reductase. The secretion of cholesterol was inhibited when cells were incubated with glucagon, norepinephrine, or dibutyryl cyclic AMP. Glucagon and dibutyryl cyclic AMP also inhibited the induction of HMG-CoA reductase. Norepinephrine treatment resulted in a decrease in the synthesis and secretion of proteins but caused an increase in reductase activity. Insulin treatment had no effect either on reductase activity or on sterol efflux from rat hepatocytes.
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PMID:The effect of glucagon, norepinephrine, and dibutyryl cyclic AMP on cholesterol efflux and on the activity of 3-hydroxy-3-methylglutaryl CoA reductase in rat hepatocytes. 22 Mar 51

Severly obese subjects and sex- and age-matched controls underwnet physical training during a 6-wk period. Evidence of training was shown in all subjects by increased aerobic power. Before training the obese subjects were characterized by the following abberations: decreased glucose tolerance, hyperinsulinemia, elevated blood glycerol and plasma free fatty acids, and a blunted plasma growth hormone response during glucose tolerance. Noradrenaline output was elevated, a finding of potential interest for the explanation of increased lipolysis, blood pressure, and heart size in obesity. With training the following changes were found:In the controls there was evidence for the beginning of a decrease of adipose tissue mass. In the obese, however, body weight, body fat, or fat cell size did not decrease during training. Plasma insulin decreased, and a corresponding increase of plasma glycerol was seen. Glucose tolerance was not changed, and this, together with decreased plasma insulin, indicated an increase insulin sensitivity of the periphery. Changes in noradrenaline or growth hormone during training could not explain this increased sensitivity. Urinary cortisol output was found to decrease after training in the obese; this might be interpreted as a decrease in cortisol secretion allowing a more effective insulin action on the periphery.
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PMID:Physical training in human hyperplastic obesity. IV. Effects on the hormonal status. 31 26

The rate of insulin, glucagon, and somatostatin secretion was measured from isolated rat islets maintained in a perifusion system. The effect of norepinephrine (NE) was simultaneously determined on the release rate of all three hormones. Norepinephrine was employed at an acute dose of 10 micrometers and in graded doses from 1 nM to 10 micrometers in the presence of high (22 mM) and low (1.4 mM) glucose conditions, insulin secretion was maximally inhibited at 10 micrometers NE concentration and was significantly depressed at 100 mM NE concentration. Under both high and low glucose conditions, glucagon release was maximally stimulated at 10 micrometers NE concentration and was significantly elevated at 10 nM NE concentration. Under high and low glucose conditions, somatostatin release was inhibited by 10 micrometers NE concentration and was significantly depressed at 100 nM NE concentration. During the initial maximal stimulation of glucagon, NE inhibition of somatostatin and insulin was prevented, possibly by the high level of glucagon released. A paracrine effect of glucagon on beta and delta cells is proposed.
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PMID:Effect of norepinephrine on insulin, glucagon, and somatostatin secretion in isolated perifused rat islets. 38 55


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