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)

The data presented concern the chemistry and biology of cardiotrop peptides and proteins isolated by us from the hypothalamus. The molecular mechanisms of the effect of neurohormone "C" (NC) as well as of a new cardiotrop hexapeptide from cattle hypothalamus are discussed. In in vitro studies on homogenates NC has been found to inhibit greatly not only 3'--5'-cyclo-AMP phosphodiesterase activity of brain and heart but also 3'--5'-cyclo-GMP phosphodiesterase activity. NC has been shown to be bound to specific proteins and to the regulatory unit of cyclo-AMP-dependent histone kinase of brain. It seems to compete with cyclo-AMP for the same proteins and is considered to be a regulator of intracellular cyclic nucleotides. NC has been shown to be combined to specific proteins in brain with non covalent bonds. A new cardiotrop hexapeptide has been shown to be present in bovine hypothalamus and its chemical structure has been found to be Tyr-Leu-Gly-Arg-Pro-Gly-amide. The acetylated form of this hexapeptide, which may be also present in brain, is much more active. The radioimmunochemical experiments carried out with antiserum 744 (from prof. Schally) by us have confirmed the existence of this hexapeptide and other fragments of LH-RH in the bovine hypothalamus. The effect of this hexapeptide on cardiac function and metabolism has been compared with a number of polypeptides (luliberin fragments). The hexapeptide has been shown to have not only cardiotropic but also a hypoglycaemic effect. It enhances the secretion of insulin and counteracts the inhibitory action of somatostatin on the insular apparatus. The hexapeptide produces significant changes in the activities of phosphorylase a and b as well as in that of phosphoprotein phosphatases. It reduces the amount of kinines in blood. Certain fractions of substance P, have been shown to have cardiotrop actitivty--they increase the rate of blood leaving the heart. The organotrop effects of a number of peptide neurohormones are discussed in connection with the hexapeptide. The results obtained have shown that the mechanisms underlying the effects of the cardioactive substances found by us are quite different. The data presented show that in brain a number of chemical factors (mainly peptides) are formed, which are involved in the regulation of heart function.
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PMID:[Chemistry and biology of hypothalamic cardioactive proteins and peptides]. 22 93

We studied the effect of adrenergic blockade on hepatic venous hyperglycemia and the activation of a hepatic glycogenolytic enzyme, phosphorylase-a, in response to cerebral cholinergic activation. Neostigmine was injected into the third cerebral ventricle of bilaterally adrenodemedullectomized (ADMX) rats, while somatostatin and insulin were administered intravenously. Hepatic venous plasma glucose concentrations and hepatic phosphorylase-a activity were measured. Intracerebroventricular injection of neostigmine (5 x 10(-8) mol) caused increases in hepatic venous glucose concentrations and hepatic phosphorylase-a activity. Both of these changes were prevented by intraperitoneal (IB) pretreatment with phentolamine (5 x 10(-7), 1 x 10(-6) mol) without the intervention of insulin secretion, but not by pretreatment with the alpha-adrenoreceptor antagonist phenoxybenzamine (1 x 10(-6) mol), the beta-adrenoreceptor antagonist propranolol (1 x 10(-6) mol), the alpha 1-antagonists prazosin or bunazosin (1 x 10(-6) mol), the alpha 2-antagonist yohimbine (1 x 10(-6) mol), or prazosin (5 x 10(-7) mol) plus yohimbine (5 x 10(-7) mol). These results suggest that phentolamine prevented brain-mediated hepatic glycogenolysis by a mechanism that may not be classified pharmacologically as involving either alpha 1- or alpha 2-receptors.
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PMID:Effects of adrenergic blockers on central nervous system-mediated hyperglycemia in fed rats. 135 Mar 17

The effect of hyperglycemia on whole body substrate utilization and the metabolic profile of skeletal muscle has been investigated. Eight glucose-tolerant men were infused with somatostatin (S) for 190 min. During the last 120 min of S infusion, glucose was infused to achieve a steady-state plasma level of 26 mmol/l. Biopsies were obtained from the quadriceps femoris muscle immediately before and 35 and 120 min after induction of hyperglycemia. Steady-state glucose disposal during hyperglycemia averaged (+/- SE) 33.8 +/- 3.2 mumol.kg fat-free mass-1.min-1, and approximately 70% of the glucose disposal was accounted for by skeletal muscle. Intracellular glucose increased from 0.9 +/- 0.2 mmol/kg dry wt during S to 9.5 +/- 2.5 during hyperglycemia (P less than 0.01). It was estimated that approximately 35% of the glucose taken up by muscle during 120 min of hyperglycemia was not phosphorylated. Muscle contents of alpha-D-glucose 1,6-diphosphate, D-glucose 6-phosphate, ATP, ADP, and AMP (both of which are based on the phosphocreatine-to-creatine ratio), which have been shown to inhibit hexokinase in vitro, did not change significantly during hyperglycemia, nor were there any significant changes in any of the other postphosphofructokinase intermediates, D-fructose 2,6-diphosphate, and citrate. Hyperglycemia did not alter the fractional activities of glycogen synthase or phosphorylase, nor total phosphorylase activity. However, hyperglycemia resulted in a 55% increase in glycogen synthase-specific activity (P less than 0.01). It is concluded that hyperglycemia results in a marked increase in muscle glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperglycemia induces accumulation of glucose in human skeletal muscle. 167 95

In rats, oral administration of BAY K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate), a dihydropyridine derivative, Ca2+-channel activator, lowers fasting glycaemia and improves glucose tolerance to carbohydrate loading without elevating peripheral plasma insulin. To study the hypoglycaemic mechanism of this compound, we have examined its effects on glucose production by isolated rat hepatocytes and on hormone secretion by the perfused rat pancreas. Incorporation of BAY K 8644 (0.2-10 microM) into the hepatocyte incubation medium failed to significantly modify glycogenolysis, gluconeogenesis or L-lactate production. Hepatocyte glycogen phosphorylase a (EC 2.4.1.1) activity and fructose 2,6-bisphosphate levels were also unaffected by BAY K 8644. In the perfused rat pancreas, BAY K 8644 markedly stimulated insulin release without modifying glucagon or somatostatin output. Thus, the possibility that this compound exerts its hypoglycaemic effect by provoking insulin secretion should be further investigated.
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PMID:In vitro effects of BAY K 8644, a dihydropyridine derivative with hypoglycaemic properties, on hepatic glucose production and pancreatic hormone secretion. 245 69

The influence of brain cholinergic activation on hepatic glycogenolysis and gluconeogenesis was studied in fed and 48-hour fasted rats. Neostigmine was injected into the third cerebral ventricle and hepatic venous plasma glucose, glucagon, insulin, and epinephrine were measured. The activity of hepatic phosphorylase-a and phosphoenolpyruvate-carboxykinase (PEP-CK) was also measured. Experimental groups: 1, intact rats; 2, rats infused with somatostatin through the femoral vein; 3, bilateral adrenodemedullated (ADMX) rats; 4, somatostatin infused ADMX rats; 5, 5-methoxyindole-2-carboxylic acid (MICA) was injected intraperitoneally 30 minutes before injection of neostigmine into the third cerebral ventricle of intact rats. MICA treatment completely suppressed the increase in hepatic glucose in fasted rats, but had no effect in fed rats. Phosphorylase-a activity was not changed in fasted rats, but increased in fed rats, intact rats, somatostatin-infused rats, somatostatin-infused ADMX rats, and ADMX rats in that order. PEP-CK was not changed in fed rats, but increased at 60 and 120 minutes after neostigmine injection into the third cerebral ventricle in fasted rats. We conclude that, in fed states, brain cholinergic activation causes glycogenolysis by epinephrine, glucagon, and direct neural innervation. In fasted states, on the other hand, gluconeogenesis is dependent on epinephrine alone to increase hepatic glucose output.
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PMID:Central nervous system control of glycogenolysis and gluconeogenesis in fed and fasted rat liver. 257 6

Somatostatin has no effect on epinephrine (adrenaline)-stimulated hepatic glucose output in the isolated perfused rat liver, which suggests that the peptide does not inhibit the phosphorylase enzyme system.
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PMID:Failure of somatostatin to inhibit epinephrine (adrenaline)-stimulated hepatic glucose output in vitro. 610 3

Effect of somatostatin on liver glycogen metabolism and lipid metabolism were studied in rats in vivo. Somatostatin infused at a rate of 100 ng/min/100 g wt. into the femoral vein resulted in a marked decrease in the blood glucose concentration. The content of glycogen in the liver and the concentration of insulin in the portal vein were also decreased during somatostatin infusion. Glucose was infused at a constant rate of 1.25 mg/min/100 g wt. in combination with somatostatin to prevent the somatostatin-induced hypoglycemia. Under this condition, significant increase in liver glycogen was observed without significant changes in the blood glucose level. The liver glycogen synthase activity did not change significantly during infusion of somatostatin and/or glucose. In contrast, the glycogen phosphorylase activity was markedly inhibited by infusion of somatostatin plus glucose. Liver glycogen phosphorylase was inversely correlated with the blood glucose level. However, there was no correlation between the phosphorylase activity and blood glucose concentration during somatostatin infusion. Infusion of somatostatin alone caused an increase in the blood free fatty acid and a marked decrease in the blood ketone bodies. Glucose-induced decrease in the blood free fatty acids and ketone bodies were partially overcome by the simultaneous infusion of somatostatin. On the basis of these findings, possible physiological roles of somatostatin in regulation of carbohydrate metabolism were discussed.
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PMID:Effects of somatostatin on liver glycogen and fat metabolism in vivo. 614 5

In this report we describe a novel in vitro phenomenon involving the interaction of insulin with purified protein phosphatases. Evidence is presented that porcine insulin is capable of activating and binding to rabbit skeletal muscle protein phosphatases in vitro. Its effects were examined on four rabbit skeletal muscle protein phosphatases. Two of these, phosphatases C-I and C-II, are of Mr approximately 35,000 and are the dissociated forms of protein phosphatase. The two other phosphatases, H-I and H-II, have Mr approximately 250,000 by gel filtration and represent nondissociated forms of phosphatase. Insulin reproducibly activated homogeneous preparations of protein phosphatase C-II and H-II approximately 3-5-fold in vitro. The activation was dependent on temperature, time, and insulin concentration. The activities of the phosphatases toward both phosphorylase alpha and histone were affected, indicating that this was not a substrate-directed effect. The activation phenomenon was not mimicked by insulin A or B chains, somatostatin, glucagon, or bovine serum albumin, and could be prevented by insulin antiserum. 125I-Insulin was shown to bind to the protein phosphatases by solid phase binding assays. Phosphatases C-I, C-II, and H-II, but not phosphatase H-I, were found to bind insulin reversibly. Half-maximal binding to the protein phosphatases was observed at approximately 5 X 10(-10) M insulin. Labeled insulin was found to coelute with protein phosphatase H-II on gel filtration when a mixture of the two was chromatographed, providing evidence for the formation of an enzyme-insulin complex. These findings suggest that certain protein phosphatases may have a specific binding site(s) for insulin and that these insulin-phosphatase complexes may also exhibit enhanced catalytic activity.
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PMID:A novel in vitro interaction of insulin with rabbit skeletal muscle protein phosphatases. 632 53

The effects of somatostatin on epinephrine's ability to stimulate glucose output have been examined in hepatocytes isolated from dogs fasted overnight. Half-maximal stimulation of phosphorylase a activity and glucose output occurred at an epinephrine concentration of approx. 5 X 10(-9) M. Somatostatin at 10, 100 or 1000 ng/ml had no effect on the ability of a maximal (1 X 10(-7) M) and a submaximal (1 X 10(-8) M) dose of epinephrine to activate phosphorylase at 2 min, or to stimulate glucose output over 20 min. Since the doses of somatostatin used in the present study are up to 50-fold higher than the blood concentrations commonly found when somatostatin is used in vivo to inhibit pancreatic hormone secretion, it seems unlikely that use of somatostatin in this way would affect stimulation of hepatic glycogenolysis by epinephrine in vivo.
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PMID:Lack of effect of somatostatin on the stimulation of hepatic glycogenolysis by epinephrine in isolated canine hepatocytes. 643 62

Phenacylimidazolium ions have the capacity to promote hepatic glycogen synthesis in vitro via activation of glycogen synthase and inactivation of phosphorylase. The purpose of the present study was to determine whether these compounds alter net hepatic substrate balance in vivo. Following a control period somatostatin was infused into 42h-fasted, conscious dogs and insulin (3X-basal) and glucagon (basal) were replaced intraportally. The glucose load to the liver was doubled with a peripheral glucose infusion and the phenacylimidazolium compound, 254236 (EX; n = 5) was infused intraportally at varying rates in four separate periods (0 (P1), 0.5 (P2), 1.0 (P3), 2.0 (P4) mumol kg-1 min-1). In a separate group of animals (C; n = 5) saline was infused intraportally during P1-P4 to match the volume rate of delivery that occurred in EX. In C net hepatic glucose uptake was 8.5 +/- 1.7 mumol kg-1 min-1 during P1 and did not change significantly throughout the study. In EX net hepatic glucose uptake increased (p < 0.05) from 9.0 +/- 2.5 during P1 to 16.2 +/- 3.1 mumol kg-1 min-1 during P4. Whereas net hepatic lactate output was evident throughout P1-P4 in C, the liver consistently switched to net lactate uptake during P3 (1.2 +/- 1.7 mumol kg-1 min-1) and P4 (2.2 +/- 1.0 mumol kg-1 min-1) in EX. Sympathoadrenal activation (increased catecholamines) was evident in EX during period 4. The increased hepatic retention of carbon (glucose and lactate) coincident with 254236 infusion in conscious dogs is less than that observed in vitro but is consistent with a role for phenacylimidazolium ions in promoting hepatic glycogen synthesis.
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PMID:Regulation of net hepatic substrate balance by phenacylimidazolium ions in the conscious dog. 791 46


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