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)

In normal dogs epinephrine stimulates glucose production (Ra) independently of glucagon. To investigate the role of this interaction in diabetes, epinephrine (0.1 micrograms . kg-1 . min-1) was infused for 90 min in five alloxan-diabetic dogs in the presence or absence of somatostatin (0.1 micrograms . kg-1 . min-1). In response to epinephrine, glycemia rose by 40% reflecting a near maximal (122%) increase in Ra. Plasma glucagon (IRG) rose to 953 pg/ml, whereas insulin (IRI) increased minimally. When somatostatin was infused with epinephrine to prevent the rise of IRG and IRI, there was only a marginal increase of glucose concentration (12%) and production (38%). The effect of somatostatin was reversed by infusing glucagon (10 ng . kg-1 . min-1) together with epinephrine and somatostatin into five additional alloxan-diabetic dogs. Increments in IRG, glycemia, and Ra were fully reestablished. A 100% FFA increase was observed in all three groups, indicating that the lipolytic effect of epinephrine was independent of glucagon. In conclusion, in diabetic dogs, in contrast to normal dogs, epinephrine induced a marked and prolonged increase in glucose concentration and production mostly through a stimulation of IRG secretion.
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PMID:Importance of glucagon in mediating epinephrine-induced hyperglycemia in alloxan-diabetic dogs. 703 19

Pancreatic hormonal and metabolic responses to chronic administration of sodium 2 chloropropionate (2 CP) were investigated in conscious dogs. We subcutaneously administered 2 CP daily for 7 days at the dose of 0.58 mmol/kg (62.5 mg/kg) in normal dogs and those rendered diabetic by injection of alloxan (0.24 mmol/kg, i.v.). In the normal dogs, the chronic administration of 2 CP provoked a decrease in blood lactate and pyruvate but not in blood glucose concentrations. Urinary oxalate was not increased by the daily injection of 2 CP. Blood ketone body concentrations progressively increased after the third day of treatment. At the same time, plasma cholesterol slowly decreased. The 2 CP chronic administration did not change the plasma somatostatin, glucagon, and insulin levels. In the alloxan-diabetic dogs, treated with insulin alone, blood glucose, ketone body concentrations, and plasma somatostatin and glucagon levels were elevated. The adjunction of 2 CP with insulin injections resulted in a fall in blood lactate and pyruvate levels and a progressive decrease of blood glucose concentrations. Blood ketone bodies, which were already high at the start, were not affected when 2 CP was combined with insulin. The hypersomatostatinemia was not decreased, whereas the hyperglucagonemia was considerably reduced. So, I/G ratio, which was strongly decreased with insulin alone, progressively returned to normal values. As to urinary compounds, 2 CP induced a marked decrease in glucosuria and did not change the elevated urinary beta hydroxybutyrate levels. In conclusion, these findings show that the adjunction of sodium 2 chloropropionate to insulin in diabetic dogs results in a reduction of hyperglycemia and hyperglucagonemia.
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PMID:Effects of chronic administration of sodium 2 chloropropionate in normal and diabetic dogs. 715 36

Adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), a P2y purinergic agonist, has been shown to be a potent insulin secretagogue on the isolated rat pancreas. In the present work the effects of ADP beta S on insulin somatostatin, and glucagon secretions were investigated in dogs. In vivo, in anesthetized fasted dogs, i.v. ADP beta S (0.1 mg kg-1) induced an immediate increase in insulin and somatostatin-like immunoreactivity (SLI) but not in glucagon pancreaticoduodenal outputs. In conscious fasted dogs, i.v. ADP beta S (0.1 mg kg-1) produced an immediate and transient augmentation in plasma insulin levels but not in plasma SLI and glucagon levels. In vitro, the effects of ADP beta S were investigated on the isolated uncinate process of dog pancreas, from normal and alloxan-diabetic animals. In normal uncinate process, in presence of 8.3 mM glucose, ADP beta S (1 microM) stimulated insulin and SLI releases but not glucagon release. On uncinate process from diabetic animals, ADP beta S (1 microM) retained its stimulating effects but the responses were impaired as compared with normal dogs: Insulin response was drastically diminished and SLI response strongly enhanced. In conclusion, ADP beta S is a potent insulin secretory agent in dog. This P2y purinoceptor agonist, which exerts a direct stimulatory effect on pancreatic SLI, is interestingly devoid of direct glucagonotropic properties.
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PMID:In vivo and in vitro effects of adenosine-5'-O-(2-thiodiphosphate) on pancreatic hormones in dogs. 780 20

We have previously shown that acute insulin-induced normalization of glycemia in alloxan-diabetic (A-D) dogs results in marked inhibition of total pancreatic glucagon content, but normalization of somatostatin content. We suggested that this glucagon deficiency might account for A-cell unresponsiveness in diabetes. To examine these changes in detail at the islet level, morphometric and immunologic analyses were carried out on pancreata from four normal (N), four hyperglycemic A-D dogs (HD), and four A-D dogs after acute normalization of glycemia with insulin (ND). The total number of islets per pancreas (3.9 x 10(6) +/- 0.5 x 10(6); determined from the number of islets per square millimetre) was reduced by 60% (p < 0.001) in HD, and this was not affected by acute normalization of glycemia. Insulin content per islet was 1247 +/- 205 pg in N, and this was reduced in both HD and ND to 2 and 5%, respectively (p < 0.001). Similarly, insulin-containing B-cell area was 76 +/- 1% of the total islet area in N, and was unmeasurable in HD and ND. Glucagon content per islet was 89 +/- 6 pg in N, and this was increased by 215% (p < 0.001) in HD, but was normalized in ND. The A-cell area increased concomitantly by 170% from 17 +/- 1 to 46 +/- 2% (p < 0.01) of islet area in HD, and remained elevated in ND.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increase in somatostatin to glucagon ratio in islets of alloxan-diabetic dogs: effect of insulin-induced euglycemia. 790 97

Intracerebroventricular (ICV) injection of carbachol elicits hormonal and metabolic responses similar to moderate stress. In normal dogs, ICV carbachol stimulated marked counterregulatory hormone release, but altered plasma glucose only marginally because the marked increment in glucose production (Ra) was almost matched by the increment of utilization (Rd), even though plasma insulin was unchanged. In alloxan-diabetic dogs, Rd did not match Ra and plasma glucose increased substantially. Since somatostatin octapeptide (ODT8-SS) inhibits some sympathetic mechanisms of the stress response, we explored the extent to which ODT8-SS can alleviate the counterregulatory responses to stress induced by carbachol, and particularly whether it can restore glycemic control in diabetes. ODT8-SS (20 nmol) was ICV-injected (1) in normal dogs (n = 5), and (2) prior to ICV carbachol before (n = 7) and after (n = 6) the induction of alloxan-diabetes. ODT8-SS did not affect basal values, but when administered before ICV carbachol there were no significant increments in plasma epinephrine, cortisol, arginine vasopressin (AVP), insulin, glucose, or lactate. There were significant increases in norepinephrine, glucagon, Ra, Rd, and the glucose metabolic clearance rate (MCR), although they were much smaller than seen previously with ICV carbachol alone. After induction of alloxan-diabetes, Rd and MCR did not change with ICV ODT8-SS and carbachol as in normal dogs, but norepinephrine, epinephrine, glucagon, lactate, plasma glucose, and Ra increased, although with the exception of glucagon these increases were much smaller than seen previously with ICV carbachol alone. ODT8-SS administered before ICV carbachol in normal or diabetic animals resulted in increased free fatty acid (FFA) levels. The increases in glycerol were less than and those in FFA greater than seen previously with ICV carbachol alone. Since ODT8-SS does not alter basal counterregulatory hormone release but suppresses the release during stress, this is a useful probe to analyze some of the metabolic responses to stress. When the response to carbachol from our previous report is compared with the responses to carbachol + ODT8-SS, it is indicated that the stress-related increase in Ra was consistent with stimulation of the sympathetic nervous system, whereas increased Rd is related to an unknown stress-related neuroendocrine mechanism that requires a permissive effect of insulin, since it was not seen in the frankly diabetic animals. We hypothesize that the stress-induced increase in Rd occurs not only in muscle but also in adipocytes, and that the somatostatin-induced attenuation of Rd decreased FFA re-esterification and consequently markedly increased stress-induced FFA release.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intracerebroventricular administration of somatostatin octapeptide counteracts the hormonal and metabolic responses to stress in normal and diabetic dogs. 791 19

Peptide YY (PYY) immunoreactive material was detected in the splenic and duodenal portions of the adult mouse pancreas, using immunocytochemical and immunochemical methods. Cells displaying PYY immunoreactivity generally occurred at the islet periphery. Double immunostaining enabled localization of PYY to a major subpopulation of the glucagon cells and to subpopulations of the pancreatic polypeptide (PP) cells and the somatostatin cells. In contrast, no PYY immunoreactivity occurred in the insulin cells. In alloxan-treated hyperglycemic mice, PYY immunoreactive cells were increased in number and distributed throughout the islets, in parallel with the glucagon, PP, and somatostatin cells. Analysis by radioimmunoassay indicated a significant increase in the concentration of pancreatic PYY after alloxan treatment in the splenic portion of the pancreas, but not in the duodenal portion. Pancreatic glucagon concentrations were not significantly changed. It is concluded that the islet content of PYY increases in alloxan diabetes, which might contribute to the accompanying alterations in islet function.
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PMID:Pancreatic peptide YY in alloxan diabetic mice. 793 96

The colon cancer cell line HT29 is a useful model to study intestinal chloride secretion. These cells have both cAMP-activated and calcium-activated chloride channels. Changes in elemental content of the cells after stimulation with agonists were determined by X-ray microanalysis in the scanning or scanning transmission electron microscope. Exposure of HT29 cells to pituitary adenylate cyclase activating polypeptide-27 (PACAP) caused a transient decrease in the cellular Cl and K concentrations, indicating (net) efflux of chloride. The effect of PACAP is inhibited by somatostatin, which is known to inhibit cAMP-activated as well as calcium-activated chloride secretion and by U-73122, an inhibitor of phospholipase C. Alloxan, an inhibitor of adenylate cyclase, did not significantly affect the PACAP-induced loss of chloride. The calcium-chelating agent EGTA inhibited the PACAP-induced loss of chloride, indicating the need for extracellular calcium ions. Also vasointestinal polypeptide (VIP) caused a decrease of the cellular chloride concentration in HT29 cells. VIP-induced loss of chloride could be inhibited by pre-treating the cells with somatostatin or UK14,304, an alpha-2 adrenergic agonist that has been shown previously to inhibit purinergically activated chloride efflux. Our results indicate that there is cross-talk between the cAMP- and the calcium-activated pathways for chloride secretion in HT29 cells.
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PMID:Effects of pituitary adenylate cyclase activating polypeptide-27 (PACAP) and vasoactive intestinal polypeptide (VIP) on chloride in HT29 cells studied by X-ray microanalysis. 1007 2

The effects of synthetic somatostatin analogue, octreotide, on fractional kidney weight (FKW), urinary protein excretion (UPE), creatinine clearance (Cl(cre)) and renal morphological changes were studied in alloxan-diabetic and non-diabetic rats comparatively. Diabetic rats were treated with twice daily s.c. injections of octreotide (2x2.5 microg) for 90 days. Untreated diabetic and non-diabetic animals were used as reference. The body weights and blood glucose levels of the animals were followed-up throughout the study period. After 90 days, FKW and renal morphology were evaluated. When compared to octreotide-treated diabetic group (O-D: 1.96+/-0. 23), normal control rats (NC: 1.24+/-0.05) showed a lower FKW (P<0. 05) and the FKW value of non-treated diabetic controls (DC: 2.74+/-0. 17) were significantly higher (P<0.05). Cl(cre) values were calculated at 45th and 90th days. At the 45th day, Cl(cre) values (ml/min) of O-D group (0.75+/-0.06) and NC group (0.56+/-0.09) were significantly lower than non-treated DC group (1.05+/-0.1) (P<0.05). However, at the 90th day no significant difference in Cl(cre) was observed. At the 45th day, UPE (mg/dl/day) was significantly higher in non-treated DC group (1000.45+/-392.38) when compared to NC group (236+/-36.59) (P<0.005) and UPE levels of O-D group were only slightly lower than that of non-treated diabetic group. At the 90th day, no significant beneficial effect of octreotide on UPE was observed. Octreotide did not prevent the histopathological changes related to diabetes. In conclusion, 5 microg/day octreotide administrations to diabetic rats for 90 days prevented renal weight increase but this treatment were insufficient to decrease the histopathological changes, UPE and increased Cl(cre).
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PMID:Octreotide administration in diabetic rats: effects on renal function and morphology. 1092 67

The aim of this study was to clarify the pattern of beta cell neogenesis in the alloxan-perfused, beta cells-depleted segment of glucose intolerant mice induced by selective alloxan perfusion. First, duct cells proliferated in the perfused segment, then cells co-expressing multiple islet hormones and transcription factors such as PDX-1, Nkx2.2, Isl1, and Pax6 were observed in duct cells, and newly formed islet-like cell clusters (ICCs) containing beta cells were recognized. In residual beta cell-depleted islets, glucagon or somatostatin and PDX-1 double-positive immature endocrine cells were recognized. Glucagon or somatostatin, insulin and PDX-1 triple-positive cells then appeared and these cells appeared to undergo terminal differentiation into beta cells. In conclusion, we demonstrated at least two different processes of beta cell neogenesis, i.e., formation of new ICCs from ductal epithelium and redifferentiation of residual non-beta islet cells in this model. In addition, transcription factors that appear in the processes of endocrine cell development may also play essential roles during beta cell neogenesis from duct cells.
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PMID:Beta cell neogenesis from ducts and phenotypic conversion of residual islet cells in the adult pancreas of glucose intolerant mice induced by selective alloxan perfusion. 1250 75

Hyperglycemia, dyslipidemia, and associated insulin resistance are hallmarks of diabetes mellitus. Purposes of the study reported here were to develop practical methods for assessment of in vivo insulin sensitivity and determine contributions of hyperglycemia and dyslipidemia to insulin resistance in the porcine model of alloxan-induced diabetes mellitus and dyslipidemia. Male Yucatan swine groups were treated for 20 weeks: control (C), high fat-fed (2% cholesterol) hyperlipidemic (H), alloxan-induced diabetic normolipidemic (D), diabetic high fat-fed (diabetic dyslipidemic, DD), and diabetic dyslipidemic treated with the lipid-lowering agent atorvastatin (DDA). Plasma cholesterol concentration increased sixfold in animals of groups H, DD, and DDA, whereas triglyceride concentration increased threefold in animals of group DD only. Diabetics had decreases in glucose tolerance and pancreatic immunostaining for insulin. Use of the gold standard hyperinsulinemic euglycemic clamp procedure indicated that maximal insulin-stimulated glucose uptake was similar to that in humans, but this method was not practical for use in pigs. Instead, a more convenient and valid insulin sensitivity test involving suppression of insulin secretion with somatostatin and a single insulin injection was used. Insulin sensitivity was greatly impaired by anesthesia with isoflurane, but was not affected by use of the anxiolytic agent diazepam. Insulin sensitivity decreased by 75% in diabetics (groups D, DD, DDA), compared with animals of groups C and H, and was inversely related to fasting blood glucose concentration (r = -0.72). Insulin treatment to restore blood glucose values of diabetics (> 250 mg/dl) to near control values (< 100 mg/dl) promptly restored insulin sensitivity to control values. We conclude that hyperglycemia is a major cause of insulin resistance in the porcine model of alloxan-induced diabetes mellitus and dyslipidemia.
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PMID:Hyperglycemia-induced insulin resistance in diabetic dyslipidemic Yucatan swine. 1262 7


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