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 diabetes or impaired glucose tolerance that occurs in most patients with pancreatic cancer is characterized by profound insulin resistance. Recent evidence suggests that the diabetes may result from the presence of the tumor rather than being a predisposing factor to development of the malignancy. Some islet hormones have been shown to exhibit diabetogenic effects. To investigate the potential role of these hormones in the diabetic state associated with pancreatic cancer, we measured islet hormones during fasting in pancreatic cancer patients (n = 30), patients with other malignancies (n = 43), and healthy controls (n = 25). Preoperative pancreatic cancer patients were classified as normal glucose tolerance (NGTT), impaired glucose tolerance (IGTT), non-insulin-requiring diabetes (NIRD), and insulin-requiring diabetes (IRD). Nine pancreatic cancer patients were studied after tumor removal by subtotal pancreatectomy. Some preoperative pancreatic cancer patients (n = 19), postoperative patients (n = 9), and controls (n = 8) were also studied during hyperglycemia and following glucagon injection. Fasting plasma C-peptide was elevated in NIRD pancreatic cancer patients compared to controls. Fasting levels of islet amyloid polypeptide (IAPP), glucagon, and somatostatin were elevated in NIRD and IRD patients. IAPP and glucagon, but not somatostatin, normalized following subtotal pancreatectomy. During hyperglycemia, increases in C-peptide and IAPP were seen only in controls and in NGTT and postoperative pancreatic cancer patients. After glucagon infusion, IAPP levels increased in controls and nondiabetic cancer patients; C-peptide levels increased in controls, nondiabetic patients, and NIRD. Responses of C-peptide and IAPP to glucagon normalized after pancreatectomy. During hyperglycemia, glucagon levels fell in all groups except IGTT patients and a decrease in somatostatin concentrations was seen in controls.
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PMID:Islet hormone secretion in pancreatic cancer patients with diabetes. 921 94

Short-chain fatty acids (SCFA) are derived from endogenous (metabolism of fat, carbohydrate, and amino acids) and exogenous (colonic fermentation) sources. To see how time of day and glucose tolerance status influenced serum SCFA concentrations, we determined serum SCFA throughout the day in 22 subjects with impaired glucose tolerance (IGT) and 10 young and eight middle-aged normal controls. On 1 day, insulin sensitivity was assessed as the steady-state plasma glucose (SSPG) level achieved during intravenous infusion of glucose insulin, and somatostatin. On another day, plasma glucose and insulin and serum SCFA levels were measured 12 times over 12 hours with subjects eating a standard diet. SSPG in young controls (5.5 +/- 1.1 mmol/L) was less than in middle-aged controls (9.3 +/- 1.6 mmol/L), which in turn was less than in IGT subjects (13.7 +/- 0.6 mmol/L; P < .01). Mean plasma glucose in IGT subjects was greater than in normal controls, and mean plasma insulin in IGT subjects was higher than in young controls but similar to the levels in middle-aged controls. Mean 12-hour serum acetate in young controls (143 +/- 13 mumol/L) was greater than in middle-aged controls (104 +/- 11 mumol/L) and IGT subjects (113 +/- 5 mumol/L; P < .05). Mean 12-hour serum propionate in young controls (3.8 +/- 0.5 mumol/L) was less than in IGT subjects (5.4 +/- 0.3 mumol/L; P < .01), with middle-aged controls being intermediate (4.6 +/- 0.3 mumol/L). Both young (1.6 +/- 0.3 mumol/L) and middle-aged (1.0 +/- 0.2) controls had lower mean butyrate than IGT subjects (3.1 +/- 0.4 mumol/L; P < .05). Levels of all three SCFA varied significantly during the day, tending to decrease after breakfast and increase transiently after lunch and dinner. It is concluded that both time of day and glucose tolerance status affect serum SCFA levels in nondiabetic humans. The results suggest that serum acetate is derived primarily from colonic fermentation, serum butyrate primarily from endogenous fatty acid metabolism, and serum propionate from both exogenous and endogenous sources.
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PMID:Time of day and glucose tolerance status affect serum short-chain fatty acid concentrations in humans. 922 36

Plasma glucose, insulin, and proinsulin concentrations were measured before and after an oral glucose challenge in 57 nondiabetic individuals. In addition, insulin-mediated glucose disposal was estimated by determining the steady state plasma glucose (SSPG) concentration after a 180-min iv infusion of somatostatin, insulin, and glucose. The plasma glucose concentration after oral glucose administration was used to divide the population into those with normal (n = 36) or impaired glucose tolerance (IGT; n = 21), and the 36 normal glucose-tolerant individuals were further subdivided into an insulin-sensitive (SSPG, < 9.0 mmol/L; n = 15) and an insulin-resistant (SSPG, > 10 mmol/L; n = 21) group. Fasting and postglucose load insulin concentrations were similar in the normal glucose-tolerant insulin-resistant and IGT groups, but were significantly higher (P < 0.02- < 0.001) than those in normal glucose-tolerant insulin-sensitive individuals. Fasting proinsulin concentrations were also higher (P < 0.002) in the normal glucose-tolerant insulin-resistant (15.1 +/- 1.5 pmol/L) and IGT (15.8 +/- 1.8 pmol/L) groups compared to those in normal glucose-tolerant insulin-sensitive volunteers (9.3 +/- 1.2 pmol/ L). However, the ratio of fasting proinsulin to insulin was identical in all three groups (0.12). When the three groups were combined, significant relationships (P < 0.001) existed between SSPG (degree of insulin resistance) and both fasting proinsulin (r = 0.59) and insulin (r = 0.66) concentrations, but not with the ratio of proinsulin to insulin (r = 0.03). These results demonstrate that fasting proinsulin and insulin concentrations are increased in insulin-resistant, nondiabetic subjects, and the more insulin resistant, the greater the increase. In contrast, the ratio of proinsulin to insulin did not vary as a function of insulin resistance. Thus, neither insulin resistance nor the need to secrete more insulin to maintain glucose tolerance necessarily leads to abnormal insulin processing by the beta-cell.
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PMID:Insulin resistance does not change the ratio of proinsulin to insulin in normal volunteers. 932 42

Cisplatin (9 mg/kg) or taxol (20 mg/kg) treatment of Wistar rats produced a sharp decrease in inducible nitric oxide synthase (iNOS) and gastrin in the pyloric region of the stomach, and an increase in iNOS and somatostatin in the pancreatic islets. Nitric oxide (NO) functions as a relaxation factor in the smooth muscle of the muscularis mucosa while gastrin plays an important role in the gastroprotection of the mucosa through NO. It is proposed that a decline of the iNOS and gastrin after cisplatin or taxol treatments is related to distention of the stomach, and possibly nausea and vomiting. Hyperglycemia and glucose intolerance after cisplatin treatment may be caused by increases of somatostatin and iNOS in the pancreatic islets. Combination therapy with cisplatin and taxol seems to ameliorate various toxicities due to these two individual drugs.
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PMID:Effects of cisplatin and taxol on inducible nitric oxide synthase, gastrin and somatostatin in gastrointestinal toxicity. 940 12

A 57 year-old Japanese man with a carcinoid somatostatinoma of the papilla of Vater is presented. He was found to have cholecystolithiasis without any symptoms. Physical examination showed no abnormal findings. Routine laboratory data gave normal results, except for glucose intolerance and an elevated somatostatin concentration. A yellowish papillary tumor was found at the papilla of Vater, and histological examination suggested the diagnosis of carcinoid. He underwent a pancreatoduodenectomy in March 1992. The gallbladder contained a single pure cholesterol stone. Histological, immunohistochemical, and electron microscopic studies resulted in the diagnosis of a carcinoid somatostatinoma of the papilla of Vater, without regional lymph node metastases. Post-operative pancreatic juice output from the total pancreatic duct drainage increased to more than 1000 mL/day. Although an anastomotic leakage of the pancreatojejunostomy was noted, the pancreatic fistula closed 8 weeks later. His postoperative somatostatin value was normal. He has been well for 54 months following surgery, without any signs of recurrence.
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PMID:Carcinoid somatostatinoma of the papilla of Vater: a case report. 963 24

Long-acting somatostatin analogs have recently become supplemental drugs in the treatment of neurofibroma because of their marked tumor growth inhibitory effect. Somatostatin is currently under extended evaluation in other cancers as a possible supplemental drug to the treatment protocols in use. The mode of action is not known. Somatostatin has been shown to cause glucose intolerance by inhibiting glucose-6-phosphate dehydrogenase (G6PD) in fish liver. Recent data generated in our laboratory indicate that it is this pathway and the transketolase reactions of the pentose cycle (PC) which are directly involved in the ribose synthesis process of pancreatic adenocarcinoma cells. In cell culture, somatostatin alone inhibited glucose carbon recycling through the PC by 5.7%, which was increased to 19.8% in combination with oxythiamine, a competitive inhibitor of transketolase. Oxythiamine produced strong apoptosis in in-vitro hosted tumor cells. We hypothesize that somatostatin- and oxythiamine-induced antiproliferative action is mediated by the inhibition of G6PD, transketolase, or both.
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PMID:Inhibition of the oxidative and nonoxidative pentose phosphate pathways by somatostatin: a possible mechanism of antitumor action. 971 Mar 24

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.
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PMID:Somatostatin release in response to glucose is impaired in chronic renal failure. 975 17

Thyrotropin-releasing hormone (TRH) has been found in the gastrointestinal tract, where it mainly exerts an inhibitory action. We used oral TRH, a stable and powerful formulation, to explore the glucoregulatory response of oral glucose tolerance test (OGTT) on obese patients with impaired glucose tolerance (IGT). Seven obese patients with IGT and eight controls were investigated. Three tests were performed on three separate days. On day 1, An oral TRH test: a 40 mg TRH tablet, was given. Blood samples for blood glucose (BG), proinsulin (PI), insulin (INS), C-peptide (CP), thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) were collected every 30 minutes for 3 hours. On day 2, an OGTT with 75 g glucose was performed. On day 3, an oral TRH test was administered 30 minutes before the OGTT, and blood was collected every 30 minutes for 3 hours. Oral-TRH had no effect on basal BG and on pancreatic hormone secretion. Oral TRH, coupled with OGTT in both controls and obese patients, led to a significant inhibition of BG (p < 0.01), of CP (p < 0.001), and of INS (p < 0.001) during the first hour of administration, and afterward, there was only a very slight increase, compared with levels after only OGTT treatment. After OGTT, PI peaked at 90 minutes (9.4+/-3 ng/mL) in controls and at 60 minutes (12.7+/-2.5 ng/mL) in obese patients. TRH application prior to OGTT inhibited PI secretion for 90 minutes in controls, whereas in obese patients PI levels were decreased, not inhibited, during the OGTT. The mechanism of the inhibitory TRH action on OGTT-induced increase of BG and pancreatic hormone secretion is not clear. It could be due to inhibition of gastric motility, and on a paracrine effect that enhances secretion of somatostatin that then suppresses INS, CP, and possibly PI levels. The partial escape of PI from the TRH blockade in obese patients with IGT might indicate a diminished functioning capability of beta-cells and that TRH cannot affect the INS processing within the beta-cells in these patients.
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PMID:Inhibitory action of oral thyrotropin-releasing hormone on the glucoregulatory response of the oral glucose tolerance test. 982 61

We evaluated the effectiveness of slow-release lanreotide, a long-acting somatostatin analogue, in the treatment of acromegaly. Eleven patients with acromegaly were recruited, six of whom had received long-term treatment with octreotide. Lanreotide 30 mg was administered by intramuscular injection every other week for 24 weeks. The frequency of injection was adjusted as clinically needed after 2 weeks. Clinical effects were evaluated, and symptoms were recorded and scored. Finger circumferences and hand volumes were measured. Serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) concentrations were determined, and an oral glucose test was done at baseline and after treatment. Symptom scores, circumferences of the fingers, hand volumes, and serum GH and IGF-1 concentrations significantly decreased during treatment. Serum GH concentrations returned to normal in five (46%) of the 11 patients, while serum IGF-1 concentrations returned to normal in three (27%). Glucose intolerance was not significantly improved at the end of treatment. Although the mean serum GH concentration was significantly decreased after treatment, it was still not suppressed by glucose. In conclusion, slow-release lanreotide, given either twice or three times a month, is effective in controlling acromegalic symptoms as well as GH and IGF-1 hypersecretion. The treatment is well tolerated and convenient for patients.
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PMID:Effectiveness of slow-release lanreotide, a long-acting somatostatin analogue, in the treatment of acromegaly. 983 Feb 78

The stimulus-secretion coupling of the insulin-producing pancreatic islet beta cell is subject to functional maturation during fetal life. We studied the maturation of a glucose-responsive insulin release from fetal rat islets and specifically investigated the impact of peptidergic regulation. To this end, islets were isolated from 21-day-old fetal rats and maintained for 7 days in tissue culture at 3.3 or 11.1 mM glucose and various supplements. In islets cultured in low glucose, acutely raising the ambient glucose concentration to 16.7 mM evoked a modest stimulation of short-term insulin release that was more pronounced in islets maintained in high glucose. Moreover, the insulin content was much higher in islets cultured in high than in low glucose. Culture with growth hormone (GH) markedly amplified both basal and stimulated short-term insulin secretion from islets maintained in either low or high glucose. Additionally, GH significantly elevated the insulin content in islets maintained in low glucose. Transforming growth factor alpha (TGF-alpha) increased basal, but not glucose-stimulated, insulin release and insulin content in islets cultured in low glucose. Gastrin, expressed in islets during fetal life, did not affect basal or glucose-stimulated insulin release, or insulin content, in islets maintained in either low or high glucose. The addition of gastrin to TGF-alpha did not affect the results obtained with the latter peptide. Gastrin-releasing peptide failed to influence basal or glucose-responsive insulin secretory rates, and insulin content, at either glucose concentration during culture. The somatostatin analog Sandostatin (octreotide acetate) neither influenced basal nor stimulated short-term insulin release at any glucose concentration present during culture, whereas the hormone significantly decreased the insulin content of islets cultured in high glucose. Pancreastatin, produced by porcine islet beta and delta cells, failed to influence basal or glucose-responsive insulin secretory rates, and islet insulin content, at either glucose concentration during culture. Culture with gastric inhibitory peptide (GIP) or glucagon-like peptide I (GLP-1), two proposed incretins, did not affect short-term insulin secretion in response to 3.3 or 16.7 mM glucose irrespective of the ambient glucose concentration during culture. To the contrary, GLP-1, but not GIP, increased the content of insulin in islets cultured in low glucose. We conclude that islet beta-cell differentiation and functional maturation of the stimulus-secretion coupling can be modulated in vitro in fetal rat pancreatic tissue by peptidergic regulation and glycemic stimulation. We suggest that GH and TGF-alpha stimulate, while somatostatin, through paracrine interaction, may inhibit, these processes. These effectors may be of regulatory significance in the in vivo development of glucose-sensitive beta cells, and defects in these mechanisms may result in glucose intolerance in adult subjects.
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PMID:Peptidergic regulation of maturation of the stimulus-secretion coupling in fetal islet beta cells. 1076 55


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