Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In normal human subjects, when plasma insulin, glucagon and growth hormone were 'clamped' at basal concentrations (by infusion of somatostatin plus replacement infusion of these hormones), infusion of Intralipid and heparin increased plasma free fatty acid (FFA) concentrations to approx. 1.3 mM, and ketone body production increased 4-5 fold to approx. 11 mumol . kg -1 . min-1. Hyperglucagonaemia did not further increase ketogenesis. In conditions of combined insulin and glucagon deficiency (by infusion of somatostatin without insulin and glucagon), administration of Intralipid and heparin increased plasma FFA concentrations to approx. 2.2 mM but a further increase in ketone body production did not accompany this increase. In these conditions hyperglucagonaemia increased ketogenesis by 2-3 fold the increment seen in control studies. Infusion of adrenaline (epinephrine) in conditions in which insulin secretion was not inhibited caused only a transient increase in plasma FFA concentrations and in ketone body production. These data indicate: (1) that in humans increased FFA availability can markedly augment ketogenesis in the absence of insulin deficiency and without hyperglucagonaemia; (2) that glucagon can increase ketone body production during insulin deficiency but not in its absence; and (3) that insulin deficiency may be accompanied by increased ketogenesis only because of a lack of its restraint on lipolysis and because of the action of glucagon. Glucagon may be important in determining the magnitude of ketone body production for a given degree of FFA availability and insulin deficiency, and may be necessary for attainment of maximal rates of ketogenesis. Adrenaline increases ketone body production in humans, but whether this is primarily due to a direct effect on the liver or is mediated through enhancement of lipolysis remains to be determined.
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PMID:Effects of free fatty acids, insulin, glucagon and adrenaline on ketone body production in humans. 704 39

Synthetic human beta-endorphin increased plasma glucose concentration when administered intracisternally in chronically cannulated, conscious, unrestrained, adult male rats. This hyperglycemic effect of beta-endorphin was blocked by prior systemic administration of naloxone, supporting mediation of the effect at opioid receptors in brain. Adrenal denervation blocked the beta-endorphin-induced increase in plasma glucose, supporting a thesis that this effect is mediated at least in part by increased epinephrine secretion. The hyperglycemic response to intracerebral beta-endorphin was also blocked by either intracerebral hemicholinium-3 or somatostatin, supporting both a cholinergic link and a somatostatin neuron in the brain mechanism regulating endorphin-induced stimulation of sympathetic outflow.
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PMID:beta-Endorphin-induced hyperglycemia is mediated by increased central sympathetic outflow to adrenal medulla. 724 53

Morphological analysis of hormone content and functional assessment of hormone secretion were conducted in beta TC-6 cells, an insulin-secreting cell line derived from transgenic mice expressing the large T-antigen of simian virus 40 (SV40) in pancreatic beta-cells. We observed by immunohistochemistry and confocal microscopy that beta TC-6 cells contain abundant insulin and small amounts of glucagon and somatostatin (SRIF). Glucagon usually co-localized with insulin, whereas cells containing SRIF did not contain insulin or glucagon. Static incubation and perifusion experiments demonstrated that beta TC-6 cells at passage 30-45 secrete insulin in response to glucose. In static incubations, maximal stimulation was achieved for glucose concentrations > 2.8 mmol/l glucose, and the half-maximal effect was observed at 0.5 mmol/l. Maximal stimulation was four times greater than HIT-T15 cells at passage 72-81, although HIT cells had a greater response over their basal levels. The magnitude of the insulin response to glucose in perifusion was 1,734 +/- 384 pmol.l-1. min and was 4.6-fold greater in the presence of 3-isobutyl-1-methylxanthine. Low amounts of glucagon were released in response to amino acids. Epinephrine (EPI), and to a lesser extent SRIF, inhibited phasic glucose-induced insulin secretion. A major portion of these inhibitory effects was mediated by pertussis toxin-sensitive substrates. Immunoblots detected the presence of the G-proteins Gi alpha 2, Gi alpha 3, and Go alpha 2. These results indicate that beta TC-6 cells are a glucose-responsive cell line in which insulin exocytosis is physiologically regulated by EPI and SRIF through Gi/Go-mediated mechanisms.
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PMID:Morphological and functional characterization of beta TC-6 cells--an insulin-secreting cell line derived from transgenic mice. 753 32

We observed in the HIT cell, a clonal insulin-secreting cell line, that epinephrine and somatostatin lower insulin mRNA levels and intracellular insulin content in addition to the well-recognized effect of these hormones to inhibit insulin secretion. To determine whether these inhibitory hormones might regulate insulin synthesis at the level of insulin gene transcription, we studied HIT cell expression of a human insulin-chloramphenicol acetyl transferase (CAT) reporter gene in the presence of glucose, epinephrine, and somatostatin. HIT cell expression of this human insulin-CAT reporter gene was responsive to glucose in a concentration-dependent manner, increasing threefold as the glucose concentration increased from 0.4 to 11 mM. Epinephrine significantly inhibited insulin-CAT reporter gene expression (61 +/- 5% of control), an effect mediated specifically by the human insulin gene promoter/enhancer sequence. Somatostatin significantly inhibited expression of the human insulin-CAT reporter gene (65 +/- 4% of control) and, to a lesser extent, expression of a control reporter gene, pRSVCAT (78 +/- 4% of control). Thus, somatostatin may inhibit insulin gene transcription by insulin gene-specific effects as well as more general effects on gene expression. Both epinephrine and somatostatin inhibited expression of the human insulin-CAT reporter gene in a concentration-dependent manner that paralleled inhibition of insulin secretion. These studies indicate that epinephrine and somatostatin lower HIT cell insulin mRNA levels in part by inhibiting insulin gene transcription. Thus, hormonal inhibition of insulin secretion may be coupled with inhibition of insulin synthesis, thereby allowing the beta-cell to match insulin supply to secretory demand.
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PMID:Regulation of human insulin gene transcription by glucose, epinephrine, and somatostatin. 790 98

Cysteamine, a specific somatostatin depleter, was given to male rats to clarify its role in relation to the renin-angiotensin-aldosterone (RAA) axis and glomerulosa cell growth. Rats received seven daily sc injections of cysteamine at doses of 50 or 150 mg/kg body weight (BW). Their adrenal weights and whole cortical thickness increased, but zona glomerulosa thickness decreased dose-responsively. Plasma renin activity (PRA) and aldosterone concentration (PAC) decreased. Similar results were observed in rats on a low or high salt diet and receiving daily doses of 150 mg/kg BW of cysteamine. In hypophysectomized rats, however, cysteamine given for seven days at daily doses of 100 mg/kg BW did not change either PRA or PAC. Adrenal weight did not change either too. Our results indicate that cysteamine suppresses the RAA axis and glomerulosa cell growth, probably through pituitary factors.
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PMID:Effects of cysteamine, a somatostatin depleter, on the renin-angiotensin-aldosterone axis and glomerulosa cell growth in rats. 795 74

To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity. 836 97

Adrenaline and somatostatin inhibit insulin secretion via pertussis toxin (PTX)-sensitive mechanisms. Since glucose-stimulated release involves inhibition of ATP-sensitive K+ (K+ATP) channels and activation of Ca2+ influx, we took advantage of the glucose-sensitive, insulin-secreting cell line INS-1 to investigate whether inhibitors of insulin release modulate membrane voltage and K+ATP channel activity in cell-attached patch-clamp experiments. We found that adrenaline, through alpha2-adrenoceptors, and somatostatin counteracted glucose-induced depolarization and action potentials. As expected, these effects were mediated via PTX-sensitive G proteins since PTX pretreatment of the cells eliminated the effects of adrenaline and somatostatin on membrane voltage. When INS-1 cells were activated by adding both the K+ATP channel inhibitor tolbutamide and the adenylyl cyclase activator forskolin, adrenaline and somatostatin still repolarized the plasma membrane. Single-channel measurements in the cell-attached mode revealed that tolbutamide closed a 40 to 70 pS K+ channel which was neither reopened by adrenaline nor by somatostatin. In parallel cell preparations, insulin secretion was measured by radioimmunoassay. Insulin release induced by glucose, forskolin and tolbutamide was abolished by adrenaline. In contrast, somatostatin attenuated insulin secretion by only 30%. After comparing the potency of adrenaline and somatostatin on membrane voltage and on insulin secretion, it is concluded that the repolarizing effect of adrenaline on membrane voltage is not sufficient to explain its potent inhibitory effect on insulin secretion.
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PMID:Adrenaline-, not somatostatin-induced hyperpolarization is accompanied by a sustained inhibition of insulin secretion in INS-1 cells. Activation of sulphonylurea K+ATP channels is not involved. 866 72

The available pharmacological treatments for portal hypertension are reviewed. Vasoconstrictor treatments include vasopressin (VP), the synthetic VP analogue tGLVP, combined nitroglycerin (NTG)-VP, somatostatin (SRIF), SRIF analogues and non-selective beta-blockers. Vasodilator treatments include short- and long-acting organic nitrates. Infusions of VP > 1.0 U/min can cause severe side-effects. tGLVP can control variceal bleeding and improve survival and causes fewer complications than VP.SRIF is as effective as tGLVP in controlling bleeding and improving survival and has minimal side effects. Beta-blockers are effective in preventing the first variceal haemorrhage and are well tolerated.
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PMID:Pharmacological treatment of portal hypertension. 881 85

The in-depth study of the pathophysiology of portal hypertension is the basis for a correct medical treatment. The backward-flow theory of portal hypertension stresses the importance of increased hepatic vascular resistance, while the forward-flow theory of portal hypertension underscores generalized vasodilation, the hyperdynamic circulation and increased portal inflow. The role of expanded plasma volume has been emphasized in recent studies. The aim of drug therapy is to normalize each one of these components. Vasoconstrictor agents, i.e. vasopressin, triglycyl-lysin-vasopressin, non selective beta-blockers, somatostatin and octreotide, try to normalize the increased portal inflow and to decrease porto-collateral blood flow. Venous vasodilators, e.g. nitrates, mainly act by decreasing portal blood outflow resistance. Spironolactone has been proposed to decrease plasma volume. The use of a combination of a vasoconstrictor agent and a vasodilator or spironolactone has been proposed to increase the efficacy of medical treatment.
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PMID:[Physiopathologic basis of medical therapy of portal hypertension in cirrhosis]. 900 19

The adverse effects of diabetes on the circulatory, visual, renal, and peripheral nervous system are commonly recognized and have been extensively studied. The effects of decreased insulin secretion or resistance to insulin action on endocrine glands have not been as carefully documented. Both clinical and animal research have demonstrated that diabetes mellitus is commonly associated with altered thyroid, adrenal and gonadal function. Some of these changes are reversed with insulin replacement therapy, but endocrine function is not always restored to normal even with rigorous glycemic control. Patients with poorly controlled diabetes exhibit basal and stimulated growth hormone (GH) hypersecretion, while patients with good metabolic control still present with diurnal and exercise-induced GH hypersecretion. In contrast, diabetes suppresses GH secretion in the rat. It is unclear why GH secretion is altered, but clinical and experimental evidence exists for diabetes-associated changes in GH-releasing hormone and somatostatin release as well as for changes in the pituitary response to these hypothalamic hormones. The thyroid hormones, T3 and T4, are usually suppressed in both humans and experimental animals with diabetes. This effect of diabetes appears to involve changes in hypothalamic thyrotropin-releasing hormone (TRH) secretion as well as changes in pituitary thyrotropin (TSH) release and direct effects at the level of the thyroid gland. Adrenal cortical function is often enhanced in diabetes, most likely due to alterations in glucocorticoid feedback responses. There is much conflicting data on adrenal medullary function in diabetes; responses to stress and exercise, however, are often abnormal. Finally, male and female reproductive function is often disrupted in diabetes. Data from animal studies suggest that the major cause is altered hypothalamic LHRH secretion secondary to diabetes-induced changes in hypothalamic neurotransmitter metabolism.
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PMID:The effect of diabetes mellitus on endocrine and reproductive function. 901 56


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