Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The common denominator of the numerous data collected from experimental studies on isolated organs, on healthy subjects and on diabetic patients, is a specific effect of sulfonylureas on insulin release in the presence (or absence) of glucose. However, there are significant differences in the capacity of the various chemical preparations active in that respect. There are biochemical data suggesting that the glyburide- and chlorpropamide-type of preparations are affecting sites of the B-cells that are different from both the glucose and the tolbutamide receptors. Thus, glibenclamide seems to be qualitatively different from the older sulfonylureas, being more a potentiator than a stimulator. Therefore, we called this type the representative of 'the second generation' drugs. The extra-B-cell actions of these drugs, predominantly the stimulation of somatostatin and the inhibition of glucagon, are favorably adding to these antidiabetic actions. In clinical therapy, these specific properties make it possible to diagnose and to treat patients successfully who were regarded before as being non-responsive to sulfonylureas and being insulin-dependent. On the basis of blood glucose decreases and C-peptide increases, a specific glibenclamide-glucose-response-test has been described which is a valuable medium for predicting the outcome of oral antidiabetic therapy.
Acta Diabetol Lat
PMID:Are the 'second generation' oral hypoglycemic agents really different? 642 11

The ability of dispersed islet cells in a perifusion system to secret glucagon and insulin in response to physiologic stimuli was investigated. Normal hamster islets were isolated by collagenase digestion and the cells dispersed by sequential digestion with collagenase and trypsin. Following a 50-min period of equilibrium in buffer with high glucose concentrations (5.0 mg/ml), glucagon secretion was stimulated by glucopenia and subsequently, inhibited by increasing the concentration of glucose. The responsiveness to glucose inhibition was significantly less in dispersed islet cells than in intact islets. However, the dispersed islet cells showed significantly greater response to arginine. Glucagon secretion by dispersed islet cells was stimulated to tolbutamide and epinephrine but somatostatin had no effect. Dispersed islet cell preparations did not augment insulin secretion in response to glucose but did secrete more insulin in response to arginine. Intact islets secreted insulin in response to glucose but not arginine. We conclude that A cells in cell suspension do not need direct contact or an intact intra-islet environment in order to respond to glucose, arginine, epinephrine, or tolbutamide but the extent of response may be influenced by paracrine effects. However, paracrine relationships may be important in determining the response of B cells to secretagogues.
 ...
PMID:Glucagon and insulin secretion by dispersed islet cells: possible paracrine relationships. 675 81

A patient with biopsy-proved biliary cirrhosis and previous gastrojejunostomy and portacaval anastomosis experienced episodes of severe hypoglycemia. She was found to have hyperinsulinemia and hyperglucagonemia. An oral glucose tolerance test showed postgastrectomy hypoglycemia. Results of the intravenous tolbutamide test were diagnostic for insulinoma, but results of the intravenous glucagon test and prolonged fast (96 hours) were not. Failure, on two occasions, to suppress C-peptide normally during insulin-induced hypoglycemia led to a diagnosis of pancreatogenous hyperinsulinemia. The pancreas showed a 10-fold increase in islet volume, with intensely positive staining with anti-insulin and anti-glucagon antiserums in addition to anti-somatostatin and anti-pancreatic polypeptide antiserums. Incidental findings at pancreatic exploration were a mesothelioma, which did not stain with anti-insulin antiserum, and, at autopsy one year later, a hepatoma.
 ...
PMID:Diagnosis of pancreatic islet hyperplasia causing hypoglycemia in a patient with portacaval anastomosis. 699 72

Long-term ingestion of high fiber diets is associated with reduced glucose concentrations during fasting and improved glucose tolerance (KG) in humans. Our objective was to determine if the beneficial effects of fiber were attributable to increased production of short-chain fatty acid (SCFA) in the large intestine. Effects of SCFA on insulin sensitivity (SI), glucose effectiveness (SG), KG and baseline concentrations of glucose, insulin, glucagon and free fatty acids were examined in unfed 20-50 kg pigs (n = 6). Animals randomly received separate portal infusions (0.32 mL.min-1) of saline, acetic, propionic, and butyric acid solutions (0.01 mmol SCFA kg body weight-1.min-1) for 7-d periods. On d 7, somatostatin and tolbutamide modified frequently sampled intravenous glucose tolerance tests were performed. SI and SG were calculated using Bergman's Minimal-Model. KG was determined by regression of log glucose curve versus time. SI, SG and KG values did not differ among the treatments (P > 0.05). Baseline concentrations of glucose, insulin, glucagon and free fatty acids were unaffected by infusion treatment (P > 0.05). Our results suggest that SCFA delivery is not directly responsible for improvements in glucose metabolism observed with long-term ingestion of high fiber diets.
 ...
PMID:Splanchnic infusions of short chain fatty acids do not change insulin sensitivity of pigs. 756 92

The aim of this work was to develop an in vitro model suitable for studying insulin secretion in amphibians and for identifying agents capable of either blocking or stimulating such a process in this group. For this purpose, pancreases from the toad Bufo arenarum were incubated for 60 min at 25 degrees with several insulin secretagogues and blockers, and the immunoreactive insulin released into the medium was measured by radioimmunoassay. Under these experimental conditions, metabolic (glucose, ketoisocaproic acid, and arginine) and nonmetabolic (K+ and tolbutamide) agents as well as glucagon and acetylcholine significantly stimulated the release of immunoreactive insulin. Conversely, somatostatin and nifedipine blocked its secretion. All these agents exerted similar effects on the mammalian pancreas. These results prove that our model is a useful tool with which to study in vitro insulin secretion in amphibians and to identify agents which affect hormone release in this group.
 ...
PMID:An in vitro model suitable for studying insulin secretion in amphibians. 763 65

The reactivity of islet cell cytoplasmic antibodies (ICA)-positive and ICA-negative sera of recent onset type 1 diabetic patients was studied in human fetal pancreata of 12-18 weeks' gestation and compared with the reactivity of these sera in adult human control pancreata. The aims of the study were: (1) to observe the presence of ICA staining in human fetal islet cells; (2) to compare endpoint titres (in Juvenile Diabetes Foundation units) of ICA-positive patient sera in fetal pancreata and adult human control pancreata. Ten ICA-positive sera and eight ICA-negative sera from newly diagnosed diabetic patients and four sera from healthy controls were tested on three human adult and eight human fetal pancreata. As in the adult control pancreata. ICA-positive sera reacted to insulin-, glucagon-, and somatostatin-positive cells of fetal pancreata of all gestational ages. This was observed both in single cells and in cells in islet-like cell clusters. Dilution of a reference serum gave similar results in both adult and fetal pancreata. In contrast, the ICA-positive patient sera yielded a striking heterogeneity in fetal as well as in adult pancreata. However, end-point titres between adult and fetal pancreata did not differ significantly (P > 0.05). In conclusion, ICA-positive sera from recent onset diabetic patients show that the expression of molecules to which ICA react is present in all islet cells and starts before week 12 of gestation.
Acta Diabetol 1994 Dec
PMID:Islet cell cytoplasmic antibody reactivity in midgestational human fetal pancreas. 788 95

To examine whether sulphonylureas influence hyperglycaemia-induced glucose disposal and suppression of hepatic glucose production (HGP) in type 2 diabetes mellitus, a 150-min hyperglycaemic (plasma glucose 14 mmol/l) clamp with concomitant somatostatin infusion was used in eight type 2 diabetic patients before and after 6 weeks of glipizide (GZ) therapy. During the clamp a small replacement dose of insulin was given (0.15 mU/kg per min). Isotopically determined glucose-induced glucose uptake was similar before and after GZ administration which led to improved glycaemic control (basal plasma glucose 12.2 +/- 1.3 vs 8.9 +/- 0.7 mmol/l; P < 0.01). Glucose-induced suppression of HGP was, however, more pronounced during GZ treatment (0.96 +/- 0.14 vs 1.44 +/- 0.20 mg/kg per min; P < 0.02). Following GZ treatment hyperglycaemia failed to stimulate glycogen synthase activity. Moreover, GZ resulted in a significant increase in the immunoreactive abundance of the insulin-regulatable glucose transport protein (GLUT 4) (P < 0.02). In conclusion, these results suggest that GZ therapy in type 2 diabetic patients enhances hepatic sensitivity to hyperglycaemia, while glucose-induced glucose uptake remains unaffected. In addition, GZ tends to normalize the activity of glycogen synthase and increases the content of GLUT 4 protein in skeletal muscle.
Acta Diabetol 1994 Apr
PMID:Effects of glipizide on glucose metabolism and muscle content of the insulin-regulatable glucose transporter (GLUT 4) and glycogen synthase activity during hyperglycaemia in type 2 diabetic patients. 804 94

The interaction of glucagon-like peptide-I (GLP-I) and galanin in clonal endocrine pancreatic cells was characterized. By Northern blot analysis the presence of GLP-I receptor mRNA was shown in B (beta TC-1 cells) and D (RIN 1048-38) cells but not in A (INR1 G9) cells, thus confirming functional data demonstrating the absence of active GLP-I receptors on glucagon-producing cells. Galanin receptors were detected on B and D cells but not on A cells. In B and D cells galanin inhibited the GLP-I stimulated adenylate cyclase activity. Treatment of insulin- and somatostatin-producing cells with GLP-I increased intracellular cAMP levels, and this was dampened by galanin, GLP-I stimulated the activity of protein kinase A in B and D cells, which was also inhibited by galanin. Galanin alone did not influence B- and D-cell function. These data show that in the endocrine pancreas B and D cells but not A cells express GLP-I and galanin receptors. The interaction of GLP-I and galanin might act in the endocrine pancreas as a physiological inhibitor of the potent incretin hormone GLP-I. Therefore, we suggest galanin is a 'decretin'.
Acta Diabetol 1995 Oct
PMID:Interaction of glucagon-like peptide-I (GLP-I) and galanin in insulin (beta TC-1)- and somatostatin (RIN T3)-secreting cells and evidence that both peptides have no receptors on glucagon (INR1G9)-secreting cells. 859 Jul 87

The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured with fura-2 in individual mouse pancreatic delta-cells identified by immunostaining for somatostatin. A majority of the delta-cells responded to 3 mM glucose with slow oscillations of [Ca2+]i (frequency, 0.1-0.4/min). In originating from a basal level of 60-100 nM and reaching peak values of 200-500 nM, the oscillations resembled those in insulin-secreting beta-cells stimulated by glucose. The rise in glucose to 20 mM resulted in a minor increase in the oscillatory frequency and sometimes in transformation of the oscillations into sustained elevation of [Ca2+]i. The addition of 3 microM L-epinephrine effectively counteracted the increase in [Ca2+]i in response to glucose. The delta-cells reacted with a sustained elevation of [Ca2+]i after raising extracellular K+ to 30.9 mM or adding 1 microM tolbutamide. Analyses using the patch-clamp technique revealed the presence of K+ channels with properties similar to the ATP-sensitive channels in pancreatic beta-cells. It is concluded that regulation of somatostatin release mimics that of insulin, with glucose induction of [Ca2+]i oscillations.
 ...
PMID:Glucose stimulation of somatostatin-producing islet cells involves oscillatory Ca2+ signaling. 859 19

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) is a nonsulfonylurea hypoglycemic agent that decreases blood glucose levels in nondiabetic and diabetic animals. In the present study, we attempted to determine the effect of A-4166 on hormone secretion from the in vitro-perfused rat pancreas and to examine the underlying secretory mechanisms. In the presence of basal glucose (3 mmol/L), A-4166 markedly stimulated insulin and somatostatin release in a concentration-dependent manner over 0.03 to 3 mmol/L. A sulfonylurea, tolbutamide, also stimulated insulin and somatostatin release. A-4166 and tolbutamide elevated the level of glucagon release; however, the change lacked a clear concentration-dependent property. A-4166 at 0.3 mmol/L and tolbutamide at 3 mmol/L exhibited maximal stimulation of insulin release to a similar extent, indicating that A-4166 is one log-order more potent than and as effective as tolbutamide. By contrast, A-4166 stimulated somatostatin release to a threefold greater extent than tolbutamide. A-4166 evoked an increase in the cytosolic free-Ca2+ concentration ([Ca2+]i) in rat pancreatic beta cells. [Ca2+]i and insulin secretory responses to A-4166 were inhibited by nitrendipine (NTD), a blocker of the L-type Ca2+ channel, and by diazoxide (DAZ), an opener of the adenosine triphosphate (ATP)-sensitive K+ channel. Furthermore, A-4166-stimulated somatostatin release was also inhibited by NTD and by DAZ. The results indicate that A-4166 and tolbutamide stimulate the release of insulin and somatostatin, and that A-4166 is much more effective than tolbutamide in releasing somatostatin, a hormone that attenuates hyperglycemia under certain circumstances. It is concluded that A-4166-induced insulin release is mediated by an increase in [Ca2+]i in beta cells. An inhibition of ATP-sensitive K+ channels and a consequent activation of L-type Ca2+ channels appear to play a key role not only in insulin secretion from beta cells, but also in somatostatin secretion from delta cells in response to A-4166.
 ...
PMID:Somatostatin and insulin secretion due to common mechanisms by a new hypoglycemic agent, A-4166, in perfused rat pancreas. 859 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>