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 anatomical distribution and volume fractions of pancreatic A cells (glucagon), B cells (insulin) and D cells (somatostatin) were evaluated by an immunoperoxidase technique in 6 diabetic cats, 6 normoglycaemic glucose-intolerant cats and 6 normal control cats. Islets lacking A cells were observed in some sections from the right lobe of the pancreas which correlated with a significantly lower A cell volume fraction in the right pancreatic lobe. Endocrine cell volume fractions in normoglycaemic glucose-intolerant cats were not significantly different from controls. Thus, a reduction in B cell volume fraction was not necessary for the occurrence of impaired glucose tolerance in these cats. However, the reduction of B cell volume fraction in the 2 normoglycaemic glucose-intolerant cats with insular amyloidosis may in part explain the more severely impaired glucose tolerance previously observed in these cats. Insular amyloidosis in our feline diabetics, as in human type II diabetics, was associated with a significant decrease in A and B cell volume fractions. In both human type II and feline diabetes mellitus, however, the reduction in B cell mass does not appear sufficient alone to lead to diabetes mellitus. Therefore, amyloid replacement of functional endocrine cells does not appear to be the primary diabetogenic event in feline diabetes mellitus, but may contribute to progression of the condition due to loss of functional B cell reserves. We thus postulate that a B cell defect precedes deposition of islet amyloid and that these amyloid deposits may thus provide an important biochemical clue to specific B cell derangements occurring in adult-onset diabetics.
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PMID:Immunohistochemical morphometry of pancreatic endocrine cells in diabetic, normoglycaemic glucose-intolerant and normal cats. 287 60

Seven patients with active acromegaly were treated with SMS 201-995, an analogue of somatostatin, for one year, the maximum dose being 100 micrograms three times a day. Three patients had impaired glucose tolerance before treatment, due to insulin resistance in two and insulin deficiency in one. In all patients treatment with the analogue slightly increased postprandial glucose concentrations and suppressed insulin concentrations for two to two and a half hours after each injection; growth hormone concentrations decreased progressively with treatment. The patient with impaired glucose tolerance due to insulin deficiency developed diabetes mellitus after four months' treatment; concomitant treatment with glibenclamide resulted in a decreased glucose concentration and increased insulin concentration. This analogue of somatostatin had only minor side effects on glucose tolerance in patients with acromegaly and may be used in patients with impaired glucose tolerance provided that glucose concentrations are monitored closely.
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PMID:Glucose tolerance during long term treatment with a somatostatin analogue. 287 4

Long-acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201-995, 50 micrograms, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201-995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201-995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201-995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3-hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side-effects. SMS 201-995, 50 micrograms, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects.
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PMID:Effects of somatostatin analogue SMS 201-995 in normal man. 287 47

The beneficial effect of the long-acting analogue of somatostatin SMS 201-995 in the treatment of acromegaly is described in three cases, and current published experience is reviewed. A total of 64 patients from 10 series have received the drug from one to 25 months, usually in doses of 50-150 micrograms every eight hours by subcutaneous injection. Clinical and chemical improvement was observed in the majority of subjects but normal 24-hour serum growth hormone levels were achieved in no more than 35 percent of this group and possibly less. We have found that higher doses, up to 1,500 micrograms per day, which have generally been free of side effects, are sometimes required to normalize growth hormone secretion. A reduction of up to 33 percent in pituitary tumor size has been reported in more than half of the 27 cases studied from four groups. Clinically important side effects are infrequent, but diarrhea, usually transient, occurred in about 13 percent, with frank steatorrhea in 2 to 6 percent of cases. Alteration in carbohydrate metabolism, such as transient glucose intolerance at the start of therapy in non-diabetic acromegalic patients, and increased sensitivity to insulin or oral hypoglycemic agents in diabetic acromegalic patients, is common. Overall, SMS 201-995 appears to be a valuable new agent for the treatment of acromegaly, but long-term safety needs to be established.
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PMID:Role of a long-acting somatostatin analogue (SMS 201-995) in the treatment of acromegaly. 287 53

The responses in plasma glucose, insulin, C-peptide, glucagon and somatostatin to an oral glucose load were studied in 10 thyrotoxic patients and 10 matched euthyroid controls. The thyrotoxic patients had higher mean fasting plasma glucose (P less than 0.05) and responded to oral glucose with an earlier peak at 30 min which was higher than the corresponding glucose level in the controls (P less than 0.05). Impaired glucose tolerance was found in 3 patients. Fasting insulin and C-peptide levels were normal in the thyrotoxic patients when corrected for the higher glucose levels. Following glucose ingestion, there was no significant difference between the areas under the insulin or C-peptide curves in patients and controls, but Seltzer's insulinogenic index was reduced in the patients (P less than 0.01) suggesting an impaired pancreatic B-cell response to oral glucose. Mean basal glucagon was normal in the thyrotoxic patients. However, while in the controls plasma glucagon became suppressed following glucose ingestion (P less than 0.0001), no significant suppression was found in the patients. In the thyrotoxic patients, mean basal somatostatin was normal, but the area under the somatostatin curve following glucose ingestion was significantly increased (P less than 0.02). Our findings suggest that decreased glucagon suppression and impaired insulin response after glucose ingestion are involved in glucose intolerance in thyrotoxicosis. Enhanced somatostatin responses to oral glucose in thyrotoxicosis may have contributed to the observed impairment in pancreatic B-cell responsiveness.
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PMID:Glucose intolerance in thyrotoxicosis roles of insulin, glucagon and somatostatin. 288 18

The present study was undertaken in order to establish the significance of glucagon in glucose intolerance in liver cirrhosis. The plasma glucose response to an oral glucose load (75 g) was determined in 10 control subjects and in 10 cirrhotic patients, after infusions of: glucagon (3 ng.kg-1.min-1) or saline (154 mmol/l); somatostatin (SRIH) (500 micrograms/h); and SRIH plus glucagon (3 ng.kg-1.min-1). Glucagon infusion did not impair glucose tolerance, neither in normal subjects nor in patients with cirrhosis. On the other hand, in both groups glucose tolerance was impaired by SRIH infusion, presumably owing to an absolute insulin deficiency. Both in normal subjects and in cirrhotic patients, SRIH plus glucagon infusion further impaired glucose tolerance, presumably as a result of excess glucagon and concomitant insulin deficiency. In conclusion, our data show that hyperglucagonemia is not an important factor in the development of the glucose intolerance in patients with hepatic cirrhosis.
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PMID:Glucagon and glucose tolerance in liver cirrhosis. 289 68

The secretory response and immunoreactive heterogeneity of glucagon was investigated in a patient with glucagonoma syndrome. After glucose administration, abnormal insulin release accompanied by glucose intolerance were observed, whereas the high glucagon circulating levels were only partially blocked after glucose or somatostatin infusion. Chromatographic fractionation of plasma samples, before and after arginine administration showed that most of the immunoreactivity eluted as true glucagon. Furthermore, when aliquots of the tumor extracts were fractionated by column chromatography or by polyacrylamide gel electrophoresis, most of the immunoreactivity eluted in the 3,500 molecular weight peak. In contrast with previous reports, our results indicate that neoplasia A cells can also manufacture and release into the bloodstream great amounts of genuine glucagon rather than larger glucagon immunoreactive forms. In spite of such findings, in this patient neither diabetes nor hyperglycemia were present.
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PMID:Secretory response and immunochemical heterogeneity of glucagon in plasma and tumor extracts of a patient with glucagonoma. 300 53

Patients with cirrhosis of the liver often have insulin resistance and elevated circulating growth hormone levels. This study was undertaken (a) to evaluate glucose intolerance, insulin resistance and abnormal growth hormone secretion and (b) to determine if GH suppression improves insulin resistance. Glucose tolerance tests (GTT), intravenous insulin tolerance tests (IVITT), arginine stimulation tests (AST) and glucose clamp studies before and during GH suppression with somatostatin were performed in a group of patients with alcohol-induced liver cirrhosis. During GTT cirrhotic subjects had a 2-hour plasma glucose of 200 +/- 9.8 ng/dl (N = 14) compared to 128 +/- 8.0 ng/dl in normal controls (N = 15), P less than 0.001. Basal GH was elevated in cirrhotic patients and in response to arginine stimulation reached a peak of 17.0 +/- 5.4 ng/ml (N = 7), compared to a peak of 11.3 +/- 1.8 ng/ml in 5 normal controls (P = NS). During IVITT patients with cirrhosis had a glucose nadir of 60.0 +/- 4.0 mg/dl (N = 9), compared to 29.0 +/- 7.0 mg/dl in controls (N = 5), P less than 0.001. Peak GH levels during IVITT were not significantly different in cirrhotics and controls. Glucose utilization rates in 4 patients with cirrhosis of the liver before somatostatin mediated GH suppression was 3.1 +/- 0.5 mg/kg/min and 6.5 +/- 1.5 mg/kg/min during somatostatin infusion, P less than 0.025. We conclude that patients with alcohol induced cirrhosis have sustained GH elevations resulting in insulin resistance which improves after GH suppression.
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PMID:Growth hormone and carbohydrate intolerance in cirrhosis. 305 69

A non-steady state dose-response study was designed to quantitate peripheral sensitivity to insulin and pancreatic responsiveness to glucose, and to assess their relative contribution to glucose intolerance in Type 2 diabetes (Type 2 DM, non-insulin-dependent). Eleven lean and eleven obese patients with mild diabetes (fasting plasma glucose, FPG, 10.3 +/- 1.0 and 9.4 +/- 0.6 mmol l-1, respectively) were examined; twenty-six lean and twelve weight-matched obese subjects served as controls. Pancreatic response was measured by sequential injection of 0.1, 0.3 and 0.9 g kg-1 glucose; peripheral sensitivity to insulin was determined from the rate of clearance (Kgluc) of 0.3 g glucose injected sequentially together with 25, 50 and 100 mU insulin kg-1 or with 0, 12.5 and 50 mU kg-1, under somatostatin infusion. The mean dose-response curve describing glucose-induced insulin release showed increased maximal capacity to secrete insulin in obese controls, while the responses of lean as well as obese Type 2 DM were reduced by more than 80%. The mean dose-response curves relating plasma exogenous insulin levels to Kgluc were similar in lean diabetics and lean controls. The curves of both obese controls and obese diabetics were shifted to the right, demonstrating similar insulin resistance. In four lean controls, sensitivity to insulin was tested also during a hyperglycemic clamp set at 10.3 +/- 0.6 mmol l-1. Hyperglycemia reduced the Kgluc at all insulin levels. Individual dose-response curves were transformed to single weighted numerical pancreatic responsiveness scores [PRS], and peripheral sensitivity scores [PSS].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin deficiency and insulin resistance in type 2 (non-insulin-dependent) diabetes: quantitative contributions of pancreatic and peripheral responses to glucose homeostasis. 311 71

Acromegaly is caused by GH-secreting pituitary adenomas and, in rare cases, by ectopic production of GRH with resultant hypersecretion of GH. Important systemic manifestations include acral enlargement, swelling, disfigurement, glucose intolerance and diabetes, hypertension, nerve entrapment, arthropathy, and cardiac disease. Tumor-related major manifestations are visual impairment, oculomotor paralysis, and hypopituitarism. Morbidity is substantial, and mortality is increased. Diagnosis should be made as early as possible by measuring plasma GH after an oral glucose load and plasma somatomedin C levels. Assessment of a pituitary lesion is best made by CT scanning in the coronal plane. Therapy is mandatory and consists of surgical removal of the pituitary adenoma (usually by the transsphenoidal route) or of the ectopic source of GRH (carcinoids or islet cell tumors). Adjunctive radiation and/or drug therapy is often necessary if complete surgical ablation of the adenoma is not possible. Radiation therapy can be administered as conventional supervoltage x-ray treatment or in the form of heavy particle beams. Drugs effective in partially lowering GH levels are bromocriptine and (not yet released) somatostatin analogues. Long-term follow-up of treated patients is important to guard against recurrence, progression, or development of hypopituitarism.
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PMID:Acromegaly. 331 99


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