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)

Abnormalities of somatostatin secretion in diabetes may be secondary to B cell damage with resulting insulinopenia or other effects of diabetogenic agents, including toxicity toward the somatostatin-producing D cells. These possibilities were evaluated in isolated perfused pancreas from normal and alloxan-diabetic rats. In normal rats 3-isobutyl-1-methylxanthine (IBMX, 1 mM), alpha-ketoisocaproic acid (KIC, 5 mM), D-glucose (27 mM), and D-glyceraldehyde (5 mM) stimulated somatostatin release. In diabetic rats 3 days after alloxan, IBMX and KIC elicited somatostatin release, whereas glucose or glyceraldehyde were without effect. In diabetic rats 14 days after alloxan, an otherwise (in normal and 3-day diabetic rats) nonstimulatory concentration of IBMX (0.05 mM) markedly stimulated somatostatin release, whereas as in 3-day diabetic rats glucose was ineffective. Insulin treatment for 2 days did not affect the somatostatin response to glucose in normal rats, did not restore a somatostatin response to glucose 3 days after alloxan, but partially restored (P less than 0.01) a response to glucose (28% of normal) 14 days after alloxan. Insulin in vitro (1 mU/ml, 20 min) failed to restore a glucose effect. Administration of alloxan (1.0 mM) for 5 min to pancreases from normal rats inhibited glucose-induced somatostatin response from 1,562 +/- 401 to 206 +/- 83 pg/15 min (P less than 0.01), whereas the response to IBMX (1 mM) was not significantly decreased. Following different time courses, both an effect of alloxan and of metabolic derangement inhibit somatostatin responses to glucose in alloxan diabetes.
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PMID:Abnormal D cell secretion in alloxan-diabetes: influence by drug and aberrant metabolism. 620 35

A 71-year-old woman with insulinoma was studied. Preoperatively, using the glucose controlled insulin infusion system (GCIIS) for glucose clamping at various blood glucose levels, autonomous insulin production was demonstrated and intravenous glucose needs for maintenance of normoglycaemia were evaluated. The results of a somatostatin suppression test, guided by the GCIIS, supported the postulation of a well differentiated beta cell adenoma with reduced storage capacity. These assumptions were later confirmed by histochemical and ultrastructural investigations. Hypoglycaemia during surgery was avoided by means of the GCIIS. Upon clamping of the plasma glucose at 90 mg/dl, 15.5 g dextrose had to be given until resection of the tumour. Immediately thereafter, a sharp rise in plasma glucose to 140 mg/dl together with a need for 4.1 U insulin showed that the insulinoma tissue had been removed completely.
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PMID:[Diagnosis and surgery of an insulinoma using a glucose-controlled insulin infusion system]. 632 14

Distinct carbohydrates influenced the in vitro permeation of the somatostatin analogue octapeptide octreotide through Caco-2 cell monolayers. Apical addition of 20 mM D-glucose or D-xylose resulted in a 2.3- or 3.4-fold increased octreotide permeation, respectively. However, supplementation with 20 mM L-glucose or 20 mM D-fructose showed no permeation enhancement. Basolateral addition of D-glucose or D-xylose had no significant effect on octreotide permeation. Apical medium supplementation with D-glucose or D-xylose increased permeation of the extracellular marker [14C]polyethylene glycol 4000, indicating that both carbohydrates directly affected the paracellular route of octreotide absorption. Presence of 1 mM phlorizin decreased octreotide permeation through monolayers in the presence of glucose on average by 12.8%, suggesting that the Na(+)-dependent glucose cotransporter might be partially involved in the enhancement of the absorption process of octreotide. Octreotide was absorbed from ligated jejunal loops of rat small intestine with an absolute absorption efficiency of about 0.3%. Coadministration of D-glucose of D-xylose resulted in a 2.2- or 1.9-fold increased absorption of octreotide, whereas D-fructose showed no effect. When the peptide was given in the presence of glucose and 1 mM phlorizin, a significant reduction of absorption enhancement could be observed. Phlorizin did not inhibit octreotide absorption, when the peptide was given in the absence of glucose. The data suggest that in vivo the active transepithelial flux of solutes such as glucose contributes to the enhancement of peptide absorption.
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PMID:Enteral absorption of octreotide: modulation of intestinal permeability by distinct carbohydrates. 763 46

Previous studies have demonstrated that in vivo injection of lipopolysaccharide (LPS) acutely stimulates glucose uptake (GU) in skeletal muscle. The purpose of the present study was to determine whether this enhanced GU is neurally mediated. In the first group of rats, a unilateral sciatic nerve transection was performed 3 h before injection of LPS, and in vivo GU was assessed using 2-[14C]deoxy-D-glucose 40 min after LPS injection. At this time, LPS-treated rats were hyperglycemic (12 mM), and insulin levels were not different from control rats. In the innervated leg, LPS increased GU 43-228%, depending on the muscle type. In contrast, LPS failed to increase GU in muscles from the denervated limb. In other experiments, somatostatin was infused to produce an insulinopenic condition before the injection of LPS. Despite insulinopenia, muscle GU was still increased by LPS. In control rats, in which the euglycemic hyperinsulinemic clamp technique was used, acute muscle denervation was shown to impair insulin-mediated GU in the presence of pharmacological, but not physiological, insulin levels. Non-insulin-mediated GU (NIMGU) was assessed in rats that were insulinopenic and hyperglycemic. In innervated muscle, NIMGU was increased 56-126 and 118-145% when the plasma glucose was elevated to 9 and 12 mM, respectively. In contrast, hyperglycemia-induced increases in NIMGU were attenuated in denervated muscle. These data demonstrate that 1) the early LPS-induced stimulation of muscle GU is mediated via a non-insulin-mediated pathway and 2) the LPS-induced increase in NIMGU in muscle is neurally mediated.
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PMID:Neural regulation of the enhanced uptake of glucose in skeletal muscle after endotoxin. 765 68

Effects of gut regulatory peptides and growth factors on the uptake of 2-aminoisobutyric acid (AIB) and 2-deoxy-D-glucose (2-DOG) were examined in differentiated ovine satellite cell cultures. Insulin and insulin-like growth factor I (IGF-I) gave maximal increases of 160-180% of controls for AIB and over 190% for 2-DOG. IGF-I showed half-maximal effects at 0.1-1 nM, and insulin at 1-10 nM. Bovine growth hormone (0.01-100 nM) had no effect. Gastrin, gastric inhibitory polypeptide (GIP), bombesin and somatostatin had no action in either the absence or presence of insulin. In primary cultures epidermal growth factor (EGF) increased the uptake of AIB (133-137%) and 2-DOG (171-176%). In clonal lines, EGF had little effect on nutrient uptake but still simulated protein synthesis.
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PMID:Effects of growth factors and gut regulatory peptides on nutrient uptake in ovine muscle cell cultures. 770 22

Insulin and somatostatin reportedly affect pancreatic acinar cell function via specific receptor binding. Theoretically peri-insular levels depend on the islet-acinar portal system, but the actual hormone levels have never been demonstrated. Rat pancreata were perfused anterogradely or retrogradely with 125I-insulin, -somatostatin, or -glucagon (each, approximately equal to 10(-11) mol/l). Tracer binding was determined from differences between influx and efflux radioactivity. Saturable binding was observed for insulin and somatostatin, but not for glucagon. Binding in the absence of unlabelled peptides was significantly higher during retrograde perfusion than during anterograde perfusion for insulin (25.9 +/- 2.6 vs 16.0 +/- 2.1%, mean +/- SD; each, n = 4; p < 0.001) and somatostatin (18.4 +/- 2.0 vs 13.6 +/- 1.2%; each, n = 3; p < 0.05). Non-specific binding was similar in both directions. These findings are attributable to endogenous hormones acting as unlabelled ligands competing with the tracers during anterograde perfusion. This conclusion was supported by the demonstration that endogenous insulin stimulation by D-glucose, but not by L-glucose, caused a decrease in labelled insulin binding only during anterograde perfusion. Displacement curves obtained during retrograde perfusion showed that interstitial concentrations of insulin and somatostatin were 7.5 x 10(-9) and 1.1 x 10(-9) mol/l, respectively. Thus, the exocrine pancreas is indeed exposed to locally high concentrations of islet hormones.
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PMID:In situ binding of islet hormones in the isolated perfused rat pancreas: evidence for local high concentrations of islet hormones via the islet-acinar axis. 775 70

The effects of glucose deficiency on growth hormone (GH)-releasing hormone (GRH) and somatostatin (SRIH) release from mouse hypothalamic fragments were investigated using an in vitro perifusion system. Fragments were perifused with Krebs-Ringer bicarbonate solution (KRB) containing 5.6 mM glucose for 3 h followed by reduced glucose concentrations in KRB for the next 2 h. GRH release was simulated by 0.7-2.8 mM glucose in an inverse concentration-dependent manner. In contrast, SRIH release was not stimulated by glucose at concentrations of 2.8 and 1.4 mM; only at 0.7 mM was there a modest stimulation of SRIH release that was comparable to the effect of 2.8 mM glucose on GRH release. The maximal stimulation of GRH and SRIH release by 0.7 mM glucose was 221 and 150%, respectively, of controls. Glucose concentrations of 11.2 and 22.4 mM inhibited GRH release but did not alter SRIH release. The glucose analog 2-deoxy-D-glucose (2-DG; 5.6-39.2 mM) also stimulated GRH release in a dose-dependent manner, and SRIH release was less sensitive to 2-DG than was GRH. The maximal stimulation of GRH and SRIH release by 39.2 mM 2-DG was 190 and 147%, respectively, of controls. Increases in GRH and SRIH release stimulated by 30 mM KCl 1 h after exposure to low glucose or 2-DG were not significantly different from those after exposure to 5.6 mM glucose. However, the SRIH response to K(+)-induced depolarization was much greater than that of GRH. The glucose intermediate pyruvate (4.9 and 9.8 mM) partially inhibited both GRH and SRIH release induced by 0.7 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential sensitivity of growth hormone-releasing hormone and somatostatin release from perifused mouse hypothalamic fragments in response to glucose deficiency. 790 85

The recently synthesized calcitonin gene-related peptide (CGRP) antagonist, human alpha-CGRP 8-37, was used to study its effects on gastric acid secretion. Four dogs with gastric fistula were used to measure the antagonist's physiologic effects in the stomach. All dogs received a bactopeptone dextrose meal (intragastric titration to pH 5.5) with either continuous CGRP 8-37 (1000 pmol/kg/hr) or saline (control). Additionally, intravenous bombesin (75-600 ng/kg/hr) and bethanechol (12.5-100 micrograms/kg/hr) was tested in the presence of the antagonist. Plasma gastrin levels also were measured via radioimmunoassay (RIA) in control and CGRP 8-37-stimulated animals. Gastric acid secretion increased by 100% with infusion of 1000 pmol/kg/hr CGRP 8-37 when compared to the control. Acid output increased 98% with both intravenous antagonist and 600 ng/kg/hr bombesin when compared to bombesin alone. However, no augmentation of acid secretion by CGRP 8-37 was shown with 25 micrograms/kg/hr bethanechol. RIA of plasma gastrin demonstrated no effect with the antagonist when given alone and did not increase bombesin-stimulated gastrin release. We conclude that CGRP 8-37 blocks native CGRP inhibitory effects on gastric acid secretion. Our findings of potentiation of acid secretion by bombesin as well as no change in gastrin levels in the presence of the antagonist is likely due to a blockage in a noncholinergic neuron to the somatostatin cell. Furthermore, CGRP 8-37 did not increase bethanechol-stimulated acid secretion, most likely due to bethanechol's (acetylcholine) nearly ubiquitous positive effects on acid secretion.
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PMID:Effect of CGRP antagonist, alpha-CGRP 8-37, on acid secretion in the dog. 791 11

Mucous cells and enteroendocrine cells of the pyloric region of the ruin lizard (Podarcis sicula campestris De Betta) have been examined by lectin histochemical and immunohistochemical methods. Binding to five plant lectins (Canavalia ensiformis, Con A; Triticum vulgare, wheat germ, WGL; Lotus tetragonolobus, winged pea, WPL; Glycine max, soybean, SBL; Arachis hypogaea, peanut, PNL) was performed to characterize glycoconjugates in the secretory products of superficial and glandular mucous cells. Lectin histochemistry revealed the presence of N-acetyl-D-galactosamine, D-galactose and N-acetyl-D-glucosamine in the pyloric superficial cells. Mucous glandular cells mainly contained neutral glycoproteins with terminal residues of galactose, N-acetyl-D-glucosamine and N-acetyl-D-galactosamine. These cells did not react with Con A after periodate oxidation-sodium borohydride reduction (Paradoxical Con A staining). In the pyloric glands three different types of endocrine cells were identified immunohistochemically: gastrin-, serotonin- and somatostatin-immunoreactive cells; VIP-, bombesin- or cholecystokinin-immunoreactive cells have not been found in the pyloric mucosa.
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PMID:Immunohistochemical investigations on the pyloric glands of the ruin lizard (Podarcis sicula campestris de Betta). 791 80

The mechanisms and site of action of somatostatin-induced inhibition of pancreatic enzyme secretion were investigated using different stimulants of pancreatic secretion acting on different sites in anesthetized rats. Administration of graded doses of somatostatin-14 resulted in a dose-related inhibition of pancreatic protein secretion evoked by 2-deoxy-D-glucose, a central vagal stimulant that acts by stimulating the dorsal vagal nuclei. The lowest effective dose of somatostatin-14 was 1.0 microgram.kg-1 x h-1; maximal effective dose was 25 micrograms.kg-1 x h-1, which resulted in complete inhibition of protein output. Similarly, somatostatin-14 at a dose of 25 micrograms.kg-1 x h-1 also completely inhibited pancreatic protein secretion in response to a physiological concentration of cholecystokinin octapeptide (CCK-8), which acts via a vagal afferent pathway. In contrast, pancreatic protein outputs evoked by bethanechol, which directly stimulates pancreatic muscarinic receptors, or electrical stimulation of the vagal trunk, which activates the vagal efferent pathway, were unaffected by somatostatin-14. In separate studies, we demonstrated that perivagal treatment with the sensory neurotoxin capsaicin impaired pancreatic responses to CCK-8 but had no effect on the inhibitory action of somatostatin-14 on pancreatic secretion evoked by 2-deoxy-D-glucose, ruling out an effect of somatostatin on the vagal afferent pathway. Similarly we also demonstrated that perineural capsaicin treatment of the celiac-superior mesenteric ganglia did not affect the inhibitory action of somatostatin. These findings indicate that somatostatin inhibits 2-deoxy-D-glucose- and CCK-8-evoked pancreatic enzyme secretion via a vagal pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin inhibits pancreatic enzyme secretion at a central vagal site. 810 34


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