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 MCR and half-disappearance time of exogenously administered somatostatin have been measured during and after cessation of a constant infusion. Studies were performed on normal volunteers and patients with chronic liver disease and failure. Immunoreactive somatostatin was measured by a sensitive and specific RIA using an antiserum directed against the core of the molecule. Normal subjects had a mean MCR of 1949 +/- 250 ml/min (28.4 +/- 4.2 ml/min . kg BW) (mean +/- SEM), similar to values found in five patients with chronic liver disease. However, patients with chronic renal failure showed a highly significant (P less than 0.001) lowering of the MCR (501 +/- 32.7 ml/min or 7.8 +/- 0.6 ml/min . kg). The rate of disappearance of somatostatin after infusion was linear for 7-10 min, after which a much slower component was observed. In normal subjects, the t 1/2 of the first component varied from 1.1-3.0 min, in patients with liver disease it varied from 1.2-4.8 min, and in patients with chronic renal failure it varied from 2.6-4.9 min. Exogenously administered somatostatin is rapidly cleared in normal subjects and patients with chronic liver disease, but the MCR in end stage chronic renal failure is markedly lowered. The kidney may have a role in the metabolic clearance of exogenously administered somatostatin, or uremia may impair catabolism nonspecifically.
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PMID:Metabolic clearance and plasma half-disappearance time of exogenous somatostatin in man. 42 6

Octreotide (Sandostatin), a potent and long-acting octapeptide analogue of somatostatin, exhibits variable metabolic effects in type 1 diabetes. We have postulated that interindividual variability in octreotide metabolism could be responsible in part for the differences in metabolic responses reported in previous clinical studies. To this end, we determined plasma levels and MCR of octreotide during 24-hour continuous SC infusion (low dose, 200 micrograms; high dose, 400 micrograms) in nine female, C peptide-negative patients with type 1 diabetes. The metabolic effects of the analogue were assessed by measuring serum glucose, free insulin, glucagon, GH, and PP levels before and at 1- to 2-hour intervals during each dose of the analogue or control (0.9% saline solution) infusion in a single-blind randomized manner. Mean daytime (0800-0000 hours) and bedtime (0000-0800 hours) serum glucose levels decreased significantly (p less than 0.05 to 0.02) during analogue therapy compared with control. Mean serum free insulin levels were significantly (p less than 0.02) greater during octreotide infusion compared with control, despite the similar daily insulin requirements. Both doses of the analogue effectively suppressed 24-hour GH by 50%, glucagon by 50%, and PP by 80%. Steady-state octreotide levels varied considerably among patients (low, mean +/- SEM), 1000 +/- 101, range 638 to 1375 pg/ml; high, mean 1940 +/- 147, range 1032 to 2462 pg/ml). Although mean MCR values were similar with both doses, we observed greater interindividual variability (low, mean 2.45 +/- 0.30, range 1.31 to 3.78 ml/kg/min; high, mean 2.36 +/- 0.19, range 1.68 to 3.48 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Continuous subcutaneous octreotide infusion: dose-response relationships between metabolic effects and octreotide clearance in patients with insulin-dependent (type 1) diabetes. 206 44

To compare the metabolic effects of pulsatile vs. continuous iv insulin infusion, normal men had two glucose-controlled iv glucose infusions using the Biostator for 260 min, during which endogenous pancreatic hormone secretion was inhibited by a somatostatin infusion and glucagon was replaced by continuous glucagon infusion. The two tests were performed at 1-week intervals, during which human insulin was infused either continuously at a constant rate of 0.2 mU kg-1 min-1 or in a pulsatile manner at a rate of 1.3 mU kg-1 min-1 with a switching on/off length of 2/11 min. Blood glucose levels and glucose infusion rates (GIR) were continuously monitored, and glucose turnover was estimated using a [3H]glucose infusion. In both tests, plasma C-peptide dropped markedly, whereas plasma glucagon levels were about twice basal values. Plasma insulin averaged 7 mU liter-1 during continuous infusion and oscillated between 1.5 and 35 mU liter-1 during pulsatile delivery. During the first 30-60 min of both tests, the glucose appearance rate and endogenous glucose production (EGP) increased, resulting in moderate hyperglycemia, which completely suppressed GIR. During the last 65 min, EGP declined, while the glucose disappearance rate and the glucose MCR increased, so that GIR increased progressively to maintain the blood glucose clamped at about 5 mmol liter-1. During this period, no significant differences were found between the two modes of insulin administration for any of the parameters studied. Thus, continuous and pulsatile insulin iv infusion, resulting in physiological peripheral plasma insulin levels, altered the glucose turnover parameters equally, in particular inhibiting EGP, which was stimulated by glucagon during the first part of the study, and stimulating peripheral glucose uptake at the end of the study period.
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PMID:Insulin oscillations per se do not affect glucose turnover parameters in normal man. 352 23

We have compared the metabolism of infused somatostatin 14 (SS14) and somatostatin 28 (SS 28) in anesthetized dogs. After iv infusion of either peptide, plasma SS-like immunoreactivity (SLI) coeluted from Bio-Gel P10 columns with the corresponding synthetic peptide marker. The hepatic extraction, renal extraction, MCR, and plasma half-life of plasma SLI and after SS28 infusion were 11.0 +/- 1.5%, 50 +/- 4.8%, 9.9 +/- 1.4 ml/kg.min, and 2.8 +/- 0.3 min, respectively. Corresponding values after SS14 infusion were 43.1 +/- 7.4%, 82.2 +/- 6.6%, 21.9 +/- 6.5 ml/kg.min, and 1.7 +/- 0.2 min. These differences between SS28 and SS14 were all statistically significant (P less than 0.05). When equimolar amounts of each peptide were given as bolus injections, both led to a significant reduction in portal venous blood flow. After the injection of SS14, the reduction in flow was short-lived and returned to baseline by 4 min. However, between 2-7.5 min after the injection of SS28, the reduction in blood flow was significantly greater than that induced by SS14, and returned to baseline only by 15 min. These studies indicate that the metabolism of plasma SLI is significantly slower during the steady state infusion of SS28 in pharmacological doses than after similar infusions of SS14. SS28 led to a more prolonged reduction in portal blood flow than SS14; this effect is probably due to its slowed metabolism. This suggests that further modification of the SS28 molecule may increase its therapeutic potential by slowing its in vivo metabolism.
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PMID:The in vivo metabolism of somatostatin 28: possible relationship between diminished metabolism and enhanced biological action. 612 5

Somatostatin (SS) was originally described as a growth hormone release inhibiting factor synthesised in the hypothalamus. Recently, SS and its receptor (SSTR) have been demonstrated in lymphoid tissues and seem to play a regulatory, largely inhibitory, role in immune responses. The aim of the present study was to check the immunosuppressive effect of a SS derived peptide, the octreotide (SMS 201-995) and to verify whether this molecule acted synergistically with FK506. An immunosuppressive effect of SMS was observed on the proliferation of rat spleen cells induced in vitro, either by polyclonal mitogens such as PHA or by alloantigens. With PHA stimulation, 10(-14) M SMS significantly enhanced the immunosuppressive action of 0.00001 microg/ml FK506. The addition of SMS in MLR (10(-11)-10(-9)M) increased the antiproliferative effect of both 0.0001 microg/ml and 0.00001 microg/ml FK506. In consideration of the extremely low concentration of both drugs that was required to obtain a good immunosuppression in vitro, we verified the association of FK506 and SMS in vivo in an allogeneic skin graft model that used Lewis (Lew) rats as donors and Brown Norway (BN) rats as recipients. BN treated with 0.1 mg/kg FK506 and 0.5-10 microg/kg SMS showed a significant increase in mean skin allograft survival time when compared to either a monotherapy or control group. None of the animals died or showed signs of drug-related toxicity. In conclusion, a combined therapy of SMS and FK506, administered at lower dosages than those that are considered therapeutic, led to an effective immunosuppression without any undesirable side effects.
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PMID:Evidence that SMS 201-995 enhances the immunosuppressive effect of FK506. 981 92