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 insulinotropic effects of alpha-ketoisocaproic acid and glucose reveal many common characteristics in vivo and in vitro. They qualify as initiators of insulin release, their action is amplified by potentiators of insulin release, and they have a similar potency at equimolar concentrations. The dynamics of insulin release evoked by alpha-ketoisocaproic acid and glucose are similar. Epinephrine completely inhibits the insulinotropic effect of glucose and alpha-ketoisocaproic acid. Mannoheptulose exhibits a complete, immediate and reversible blockade of glucose-induced insulin release. In contrast, inhibition of alpha-ketoisocaproic acid-induced insulin release occurs after a lag period and is not reversed by removal of the inhibitor. alpha-ketoisocaproic acid, at equimolar concentrations, is several-fold more effective than glucose in elevating cAMP content in islet. alpha ketoisocaproic acid and glucose are about equally effective in stimulating somatostatin release from isolated rat pancreatic islets. This stimulation is inhibited by epinephrine. Mannoheptulose inhibits only somatostatin release induced by glucose but not by alpha-ketoisocaproic acid. It suggested that the insulinotropic characteristics of glucose and alpha-ketoisocaproic acid reveal many common features, while their mode of action appears to be different.
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PMID:Comparison of alpha-ketoisocaproic acid and glucose in rats: effects on insulin and somatostatin release and on islet cAMP content. 21 60

The effects of somatostatin and epinephrine have been studied with regard to glucose-induced insulin release and (45)Ca(++) uptake by rat pancreatic islets after 2 days in tissue culture and with regard to (45)Ca(++) efflux from islets loaded with the radio-isotope during the 2 days of culture. (45)Ca(++) uptake, measured simultaneously with insulin release, was linear with time for 5 min. (45)Ca(++) efflux and insulin release were also measured simultaneously from perifused islets. Glucose (16.7 mM) markedly stimulated insulin release and (45)Ca(++) uptake. Somatostatin inhibited the stimulation of insulin release by glucose in a concentration-related manner (1-1,000 ng/ml) but was without effect on the glucose-induced stimulation of (45)Ca(++) uptake. Similarly, under perifusion conditions, both phases of insulin release were inhibited by somatostatin while no effect was observed on the pattern of (45)Ca(++) efflux after glucose.Epinephrine, in contrast to somatostatin, caused a concentration-dependent inhibition of the stimulation of both insulin release and (45)Ca(++) uptake by glucose. Both phases of insulin release were inhibited by epinephrine and marked inhibition could be observed with no change in the characteristic glucose-evoked pattern of (45)Ca(++) efflux (e.g., with 10 nM epinephrine). The inhibitory effect of epinephrine on (45)Ca(++) uptake and insulin release appeared to be mediated via an alpha-adrenergic mechanism, since is was abolished in the presence of phentolamine. Somatostatin inhibits insulin release without any detectable effect upon the handling of calcium by the islets. In contrast, inhibition of insulin release by epinephrine is accompanied by a partial inhibition of glucose-induced Ca(++) uptake.
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PMID:Somatostatin- and epinephrine-induced modifications of 45Ca++ fluxes and insulin release in rat pancreatic islets maintained in tissue culture. 33 17

1. Investigation of the ionic requirements of the in vitro insulin release system, which consists of cod islet plasma membrane and rabbit islet granules incubated at pH 6.5, showed that the presence of Ca(2+) was obligatory for the system to operate.2. Glucose-initiated insulin release was as effective in the presence of beta-gamma-methylene ATP, as it was in the presence of ATP. This analogue of ATP is a substrate neither for adenylate cyclase nor for any known animal membrane proteases. The effect of ATP on glucose mediated release is allosteric.3. Glucose (16 mM)-initiated insulin release was slower than that induced by glucose-6-phosphate (4 mM); 150 and 120 sec, respectively.4. The lag found with glucose-mediated insulin release was dependent upon glucose concentration. The lower the glucose concentration, the longer the lag. With 1 mM glucose the lag extended to 30 min.5. Once insulin release was initiated, the rate and amount of insulin release was independent of the glucose concentration.6. Pre-incubation of membranes with Ca(2+), glucose and ATP prior to the addition of granules, abolished the extended lag that had been obtained with 1 mM glucose. Events in the plasma membrane are the major contributor to the generation of the extended lag.7. The glucose analogue 5'thio-D-glucose, although not able to release insulin, was shown to compete with glucose for the glucoreceptor. By increasing the ratio of analogue to glucose the lag time increased. Thus, the lag time is dependent upon the ;effective' external glucose concentration.8. The max. amount of insulin released by 4 ng of membrane in the presence of glucose (16 mM) was 300 ng. The fact that membranes became refractory to glucose after this max. amount of insulin was released showed that recycling of release sites was not taking place in vitro and that granule: granule interactions were not occurring.9. The 120 sec lag before glucose-6-phosphate-initiated release was independent of glucose-6-phosphate concentration. The rate of insulin release with glucose-6-phosphate was concentration dependent.10. Glucose-6-phosphate did not cause further insulin release from a membrane that had released the max. amount of insulin it was capable of in the presence of glucose. The addition of tolbutamide (10 mM) to such a membrane did cause insulin release. This suggests that glucose and glucose-6-phosphate share a final common pathway.11. Adrenaline and somatostatin did not inhibit glucose-mediated insulin release.
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PMID:An in vitro system for studying insulin release: effects of glucose and glucose-6-phosphate. 33 48

The present study was conducted to determine if glucagon release is involved in the hyperglycemic response to epinephrine and isoproterenol in the fasted and fed, unanesthetized rabbit. Epinephrine produced dose-related increases in plasma glucose and glucagon levels in fed and fasted rabbits whereas isoprotereol produced modest hyperglycemia without hyperglucagonemia. Infusion of somatostatin suppressed epinephrine-induced glucagon release and this was correlated with a 50% reduction in the hyperglycemic response. These data suggest that epinephrine-induced glucagon release is the primary reason for the difference in hyperglycemic activity between epinephrine and isoproterenol in the unanesthetized rabbit.
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PMID:Catecholamine-induced changes in plasma glucose, glucagon and insulin in rabbits: effects of somatostatin. 36 31

Normal subjects were infused 1) with epinephrine (50 ng/(kg.min)) for 180 min followed by epinephrine plus glucagon (3 ng/(kg.min)) for 60 min after which the epinephrine infusion rate was increased (125 ng/(kg.min)) or 2) with epinephrine plus somatostatin (500 microgram/h) for 180 min. Epinephrine increased glucose production and plasma glucagon transiently but caused persistent suppression of glucose clearance and sustained hyperglycemia (despite increased plasma insulin and gluconeogenic substrates); glucose production increased again on addition of glucagon and on increasing the epinephrine infusion rate. During epinephrine plus somatostatin, glucose production still increased transiently, but further suppression of glucose clearance caused more marked hyperglycemia. In conclusion, 1) in man hyperepinephrinemia within the physiological range caused sustained suppression of glucose clearance but only a transient increase in glucose production; 2) this transient hepatic response a) was not due to glycogen or substrate depletion, b) occurred without changes in plasma glucagon or insulin, c) was specific for epinephrine but permitted subsequent responses to changes in plasma epinephrine; 3) epinephrine can serve as a physiological regulator of glucose homeostasis in man both by increasing glucose production and by decreasing glucose clearance.
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PMID:Differential effects of epinephrine on glucose production and disposal in man. 49 14

Epinephrine and saline or cyclic somatostatin were infused into normal persons to study the effect of somatostatin on free fatty acid (FFA) release. Somatostatin had no effect on epinephrine-induced hyperglycaemia. It enhanced basal and epinephrine-induced FFA release, while the release of both immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) was inhibited. We suggest that the rise in FFA levels may be due to either inhibition of IRI or another effect of somatostatin on fatty acid metabolism.
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PMID:The effect of somatostatin on epinephrine-induced free fatty acid release in normal man. 60 11

Hypothalamic catecholaminergic influences on prolactin release were investigated in vitro. Both dopamine and norepinephrine caused long lasting inhibition of prolactin release from either an isolated hemipituitary or a hemipituitary coincubated with a hypothalamus. Epinephrine also inhibited prolactin release. L-Dihydroxyphenylalanine (L-dopa) inhibited prolactin release from pituitaries in the presence of a hypothalamus but not in isolated pituitaries. DL-Threodihydroxyphenylserine (threodops), serotonin, 5-hydroxy-L-tryptophan (5-HTP), tyramine, octopamine, synephrine, thyrotropin-releasing hormone (TRH), luteinizing hormone releasing hormone (LH-RH), and somatostatin all failed to alter prolactin release. Results confirm that dopamine and norepinephrine directly inhibit prolactin release from pituitary and suggest that the hypothalamic mechanism inhibiting prolactin involves dopamine but not norepinephrine.
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PMID:Hypothalamic catecholaminergic effects on prolactin release in vitro. 63 83

Somatostatin (1 mug/ml) inhibited glucose (16.7 mM)-stimulated 45Ca uptake by isolated rat islets incubated in media containing no added calcium or calcium at a low concentration (0.2mM). Epinephrine (50 mug/ml) and mannoheptulose (20mM) also inhibited 45Ca uptake by islets incubated in the presence of calcium (0.2mM). Addition of glucose (16.7 mM) caused a small but significant increase in insulin release from islets incubated in media containing no added calcium. In the presence of a low concentration of calcium (0.2 mM), glucose caused a much greater increase in insulin secretion which was inhibited by addition of somatostatin, epinephrine or mannoheptulose.
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PMID:Inhibition of calcium uptake by somatostatin in isolated rat islets of Langerhans. 78 58

Adrenaline inhibits insulin secretion via pertussis toxin-sensitive mechanisms. Since voltage-dependent Ca2+ currents play a key role in insulin secretion, we examined whether adrenaline modulates voltage-dependent Ca2+ currents of the rat insulinoma cell line, RINm5F. In the whole-cell configuration of the patch-clamp technique, dihydropyridine- but not omega-conotoxin-sensitive Ca2+ currents were identified. Adrenaline via alpha 2-adrenoceptors inhibited the Ca2+ currents by about 50%. Somatostatin which also inhibits insulin secretion was less efficient (inhibition by 20%). The hormonal inhibition of Ca2+ currents was not affected by intracellularly applied cAMP but blocked by the intracellularly applied GDP analog guanosine 5'-O-(2-thiodiphosphate) and by pretreatment of cells with pertussis toxin. In contrast to adrenaline and somatostatin, galanin, another inhibitor of insulin secretion, reduced Ca2+ currents by about 40% in a pertussis toxin-insensitive manner. Immunoblot experiments performed with antibodies generated against synthetic peptides revealed that membranes of RINm5F cells possess four pertussis toxin-sensitive G-proteins including Gi1, Gi2, Go2, and another Go subtype, most likely representing Go1. In membranes of control but not of pertussis toxin-treated cells, adrenaline via alpha 2-adrenoceptors stimulated incorporation of the photo-reactive GTP analog [alpha-32P]GTP azidoanilide into pertussis toxin substrates comigrating with the alpha-subunits of Gi2, Go2, and the not further identified Go subtype. The present findings indicate that activated alpha 2-adrenoceptors of RINm5F cells interact with multiple G-proteins, i.e. two forms of Go and with Gi2. These G-proteins are likely to be involved in the adrenaline-induced inhibition of dihydropyridine-sensitive Ca2+ currents and in other signal transduction pathways contributing to the adrenaline-induced inhibition of insulin secretion.
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PMID:Involvement of pertussis toxin-sensitive G-proteins in the hormonal inhibition of dihydropyridine-sensitive Ca2+ currents in an insulin-secreting cell line (RINm5F). 168 Aug 55

We used isolated islets of lean and obese Zucker rats to determine whether inhibitory pathways mediated by pertussis toxin-sensitive guanyl nucleotide-binding (Gi) proteins contribute to hyperinsulinemia in obese rats. Epinephrine (10(-4) M) and somatostatin (10(-7) M) inhibited insulin secretion by +/- 75% in lean and fa/fa rats. Overnight culture of islets with pertussis toxin (300 ng/ml) enhanced insulin release more in lean (+/- 120%) than obese (+/- 60%) rats. In lean rats incubation of pertussis toxin-treated islets with epinephrine resulted in lower immunoreactive insulin release (p = 0.0005) than pertussis toxin-treated islets without epinephrine. However, in obese rats pertussis toxin treatment reversed this inhibition. Pertussis toxin completely reversed inhibition by somatostatin in both phenotypes. Galanin had no effect on insulin secretion. Cellular cAMP content was similar in lean and obese rats. Inhibitory hormones had no effect on cAMP production. We conclude that islets of obese rats respond normally to inhibitors of insulin release. Reversal of somatostatin-induced inhibition by pertussis toxin indicates normal function of Gi in obese rats. A subtle difference in sensitivity to pertussis toxin between lean and obese islets was noted.
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PMID:Effect of pertussis toxin on islet insulin secretion in obese (fa/fa) Zucker rats. 170 22


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