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)

SMS 201-995 (Sandoz Pharmaceuticals, East Hanover, NJ) is a synthetic peptide analog of native somatostatin that has been used to relieve symptoms caused by neuroendocrine tumors. Reports have described an insulin suppressive effect of SMS 201-995 that results in elevations of blood glucose. We report a patient with a metastatic small bowel carcinoid and renal failure in whom mild symptomatic hypoglycemia occurred 30 to 60 minutes after SMS 201-995 administration. No increase in insulin or decreases in glucagon, cortisol, or catecholamines were observed during these hypoglycemic episodes. Elevated levels of growth hormone fell gradually following SMS 201-995 administration and did not temporally correspond to the 30- to 60-minute nadir of blood glucose. However, SMS 201-995 levels peaked during this 30- to 60-minute period. As clinical experience with this drug broadens, patients whose glucose control is dependent on counter-regulatory hormones should be monitored for the possibility of hypoglycemia.
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PMID:Hypoglycemia after administration of somatostatin analog (SMS 201-995) in metastatic carcinoid. 260 30

Fig. 5 provides a summary of the natural history of diabetic nephropathy in IDDM patients. The figure also includes the possibilities of intervention in the various stages of diabetic nephropathy. GFR values in normals are shown by the hatched area in the upper part of the figure. The lower part shows development of albuminuria. The level 20-200 micrograms/min is the microalbuminuric range. At present it is not possible to predict a malignant course either from the parental history (1), or from the prediabetic course (2). Neither at clinical diagnosis of diabetes, can complications be predicted (3). The figure shows a typical course in a patient developing diabetes at the age of 14 years. The patient showed poor metabolic control as indicated by the high level of GFR (greater than 150 ml/min) (4) and the increasing albumin excretion rate (4). At the age of 22 years the patient developed microalbuminuria (5) and later clinical nephropathy at age 30 years, typically after 16 years of diabetes. Blood pressure rises, and GFR starts to decline during incipient diabetic nephropathy with increasing microalbuminuria (greater than 70 micrograms/min) (5) (6), and end-stage renal failure reached at the age of 40 years,--if intervention is not undertaken. Intervention is possible as follows: A) hyperfiltration may be reduced by non-glycemic intervention such as a moderate reduction of protein intake, treatment with aldose reductase inhibitors (work in progress) or acute administration of a somatostatin analogue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of blood pressure intervention on renal function in insulin-dependent diabetes. 261 18

The glucagonoma syndrome is characterized by a necrolytic migratory erythematous rash, angular stomatitis, painful glossitis, a normochromic normocytic anemia, mild diabetes mellitus, weight loss, a tendency to thrombosis, and neuropsychiatric disturbances. The diagnosis is made by finding a high plasma glucagon concentration in the absence of any other cause, such as renal failure or severe stress. A pancreatic alpha-cell tumor can be identified and stained by immunocytochemistry with glucagon antibodies. Optimal treatment is surgical removal, but approximately 50 percent of the tumors have metastasized by the time of diagnosis. Since the tumor is slow-growing, remission can be obtained by hepatic artery embolization to shrink hepatic secondaries or by shrinkage, in about 10 percent of patients, with the combination chemotherapeutic regimen of 5-fluorouracil and streptozotocin. The rash frequently responds to administration of zinc, a high-protein diet, and control of the diabetes with insulin. Alongside the alpha cell in the islets of Langerhans is the D-cell, which produces somatostatin and may well act physiologically as a paracrine inhibitor of glucagon release. A newly developed, long-acting somatostatin analogue, SMS 201-995, which the patient can self-administer as a subcutaneous injection, has proven effective in suppressing glucagon secretion from glucagonomas and, in some cases, causing remission of clinical symptoms.
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PMID:Glucagonoma syndrome. 288 77

Circulating forms of somatostatinlike immunoreactivity (SLI) in humans were characterized using several chromatographic techniques. After gelfiltration chromatography on Bio-Gel P-6 columns greater than 90% of circulating SLI was of high molecular weight (MW) and eluted in the void volume. When plasma samples were passed through protein A-Sepharose columns, more than 85% of the high MW SLI was removed, indicating that this form of plasma SLI is mainly due to cross-reacting immunoglobulins. Extraction of 10-ml plasma samples from normal subjects on octadecyl silyl silica cartridges eliminated the high MW material. In addition, this extraction technique concentrated the two lower MW forms of SLI, which coelute on gel filtration chromatography with somatostatin-28 (S-28) and the tetradecapeptide form of somatostatin (S-14), respectively. Extracted plasma SLI was further analyzed by high-pressure liquid chromatography (HPLC). The results confirmed the identity of S-28 and demonstrated that S-14 is converted, in part, to Des-Alasomatostatin (S-13) following secretion into the circulation. At least four forms of SLI are thus present in human plasma: cross-reacting immunoglobulins, S-28, S-14, and S-13. Concentrations of SLI forms in the plasma of normal controls and patients with renal failure or cirrhosis were measured to assess the role of circulating somatostatin in health and disease. High MW SLI was elevated above normal in the plasma of patients with cirrhosis, but was not significantly elevated in patients with chronic renal failure. On the other hand, concentrations of plasma S-28 and S-13/14 (total concentrations of S-13 plus S-14) were elevated in patients with either chronic renal failure or cirrhosis.
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PMID:Circulating forms of somatostatinlike immunoreactivity in human plasma. 396 83

We used intravenous synthetic somatostatin to stem severe bleeding from oesophagites and oesophageal ulcer associated with renal failure hyponatremia and mental confusion. The ability of somatostatin to reduce splanchnic blood flow and portal pressure and to inhibit both gastrin release and the pentagastrin-stimulated secretion of gastric acid and pepsin provides its therapeutic use in multiple alimentary bleeding. When patients is considered poor candidate for surgery, somatostatin may prove a particularly valuable alternative to conventional medical treatments. We observed no side effects, with somatostatin, during a 72 h period of treatment. Since cimetidine give rise to mental confusion in ureamia or hyponatremia, somatostatin should be looked upon with particular interest in cases of gastro-intestinal bleeding associated with renal insufficiency.
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PMID:[Effects of somatostatin in oesophagal bleeding (author's transl)]. 610 75

The aim of the present study was to evaluate the insulin and glucagon responses to various stimuli in patients following pancreatic transplantation. Four Type 1 (insulin-dependent) diabetic patients with end-stage renal failure who had received a cadaveric segmental, neoprene-injected, pancreas transplant, in association with kidney transplantation, were investigated. Free-insulin, pancreatic glucagon, and growth hormone concentrations were measured after both oral and intravenous glucose tolerance tests, and following tolbutamide, arginine and arginine plus somatostatin infusions. Tests were performed 1 month (three cases) and 30 months (one case) after surgery, when no insulin administration was required. Four non-diabetic kidney grafted patients, matched for duration of graft survival and immunosuppressive treatment (steroids, azathioprine and anti-lymphocyte-globulins), served as control subjects. Impaired glucose tolerance was present in all diabetic and control patients. This was possibly related to immunosuppressive treatment. In comparison with control subjects, insulin release was normal in response to arginine and tolbutamide but was reduced in response to oral and intravenous glucose, while glucagon and growth hormone release were similar in both groups. Somatostatin was less effective in diabetic patients than in control subjects in suppressing insulin and glucagon release.
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PMID:Endocrine responses of type 1 (insulin-dependent) diabetic patients following successful pancreas transplantation. 613 51

Fifteen patients with chronic renal failure (serum creatinine level greater than 5 mg/dl) of long duration (more than 2 years) requiring hemodialysis were studied. Blood samples before and after 4 hours of hemodialysis were assayed for creatinine, blood urea nitrogen, potassium, calcium, glucose, insulin, gastrin, gastric inhibitory polypeptide, vasoactive intestinal polypeptide, pancreatic polypeptide, somatostatin, motilin, and neurotensin levels. Before dialysis, serum gastrin was minimally increased whereas gastric inhibitory polypeptide and pancreatic polypeptide were grossly increased compared with normal fasting values. Hemodialysis produced no changes in serum gastric inhibitory polypeptide, vasoactive intestinal polypeptide, pancreatic polypeptide, somatostatin, motilin, and neurotensin. Slight increases in serum insulin and gastrin levels may have occurred secondary to a dialysis-induced increase in the serum calcium level. The kidneys appear to be a major site of inactivation of insulin, gastrin, gastric inhibitory polypeptide, and pancreatic polypeptide. The gastrin level, although elevated in renal failure patients, may be suppressed by very high circulating levels of gastric inhibitory polypeptide.
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PMID:Chronic renal failure: effect of hemodialysis on gastrointestinal hormones. 615 Jun 57

Continued haemorrhage from oesophageal varices despite adequate injection sclerotherapy and tamponade has a high mortality rate. Such patients are usually referred for surgery. Over a 10-year period, 30 patients (21 men and nine women of median age 52 (range 21-70) years) with acute variceal haemorrhage uncontrolled by initial treatment underwent early emergency oesophageal transection. Portal hypertension was caused by alcoholic cirrhosis in 22 patients; other forms of cirrhosis were present in seven and portal vein thrombosis in one. Hepatic function immediately before operation was Pugh grade A in two patients, B in six and C in 22. Deterioration between admission and transection from grade A to B occurred in one patient and from B to C in five. Oesophageal transection stopped variceal haemorrhage in 29 of the 30 patients. Rebleeding from gastric varices within 35 days of surgery occurred in five patients. Postoperative haemorrhage also occurred from perioesophageal vessels (two patients), a gastrotomy (one) and oesophageal ulceration (two). Hepatic failure developed in seven patients, renal failure in five and both hepatic and renal failure in four. Mortality at 30 days occurred in neither of the two patients with liver function of grade A, in one of six of grade B and in 18 of 22 of grade C. The overall 30-day mortality rate was thus 63 per cent. Mortality was related to the preoperative Pugh grade (hazard ratio 3.95 per grade; P = 0.013) and preoperative blood transfusion (hazard ratio 1.37 per unit; P = 0.035). Four of six patients with grade B liver function died within 3 months and 21 of 22 with grade C disease within 1 year. Oesophageal transection is effective at stopping variceal bleeding but does not modify the underlying disease. Caution is urged for patients with grade C hepatocellular impairment proceeding to acute oesophageal transection after initial sclerotherapy. Such patients may benefit more from treatment with somatostatin or an intrahepatic porta-systemic stent shunt while awaiting definitive therapy.
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PMID:Emergency oesophageal transection for uncontrolled variceal haemorrhage. 792 95

Secretion of growth hormone (GH) is excessive in acromegaly, but also in a number of other pathological states such as anorexia nervosa, insulin-dependent diabetes mellitus (IDDM), liver cirrhosis, depression, renal failure and GH-insensitivity syndrome. Abnormalities in the neuroendocrine control of GH secretion and/or a state of insensitivity to GH contribute to hypersecretion of GH in these states, with the possible exception of acromegaly, which appears to be a primary pituitary disease. GH hypersecretion may also occur in neonates or adolescents with tall stature, thus reflecting particular physiological or paraphysiological conditions. In the cohort of brain neurotransmitters, catecholamines and acetylcholine reportedly play a major role in the control of neurosecretory GH-releasing hormone (GHRH) and somatostatin (SS)-producing neurons, and hence GH secretion. Activation of alpha 2-adrenoceptors or of muscarinic cholinergic receptors in the hypothalamus stimulates GH release, probably through stimulation of GHRH and inhibition of SS release, respectively. Activation of dopamine receptors likewise stimulates GH release, while activation of beta-receptors inhibits GH release through stimulation of hypothalamic SS function. This review discusses the involvement of brain catecholamines and acetylcholine in GH hypersecretory states, including anorexia nervosa, acromegaly, IDDM, liver cirrhosis, depression, renal failure and GH insensitivity syndrome, with a view to providing a fuller understanding of their pathophysiology and, whenever possible, diagnostic and therapeutic implications.
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PMID:Involvement of brain catecholamines and acetylcholine in growth hormone hypersecretory states. Pathophysiological, diagnostic and therapeutic implications. 858 28

Gastrin circulates at higher than normal concentrations in patients with end-stage renal failure (ESRF). However, it remains unclear which forms of gastrin are elevated and whether there is also an alteration in the secretory profile after stimulation. In the present study all processed and partially processed forms of circulating gastrin were measured in plasma before and after meal stimulation in ESRF patients and control subjects. Since Helicobacter pylori (HP) infection affects gastrin secretion, HP status was determined. Fasting gastrin-amide (36 +/- 8 pmol/L), gastrin-Gly (55 +/- 16 pmol/L), and total gastrin (218 +/- 32 pmol/L) measured in ESRF/HP-patients were all significantly greater than those in the control group (10 +/- 1, 15 +/- 3, and 17 +/- 2 pmol/L, respectively; P < 0.01). Plasma gastrin-amide (126 +/- 67 pmol/L) and total gastrin (397 +/- 164 pmol/L) were highest in the ESRF/HP+ patients. The proportion of nonamidated gastrin products was 4-fold higher in ESRF patients than in control subjects, suggesting structure-specific changes in gastrin secretion and metabolism, and this was confirmed by chromatography. The meal-stimulated increments in control/HP- and ESRF/HP-groups were similar. However, the ESRF/HP+ group had a markedly potentiated gastrin response. Fasting plasma somatostatin, an inhibitor of gastrin secretion, was also measured and was significantly lower in the ESRF patients than that in the control group. These studies show that the hypergastrinemia associated with renal failure has been underestimated. This is because only amidated products were measured. The potentiated gastrin meal response in ESRF attributed previously to changes in gastrin metabolism are in part explained by the effect of HP infection. The observed diminished somatostatin response suggests that the increase in circulating gastrin in ESRF is the result of loss of inhibition of secretion as well as decreased metabolism. As both amidated and nonamidated gastrin are now considered to have trophic and secretory effects, these findings may explain the gastrointestinal tract hypertrophy often associated with ESRF.
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PMID:Gastrin processing and secretion in patients with end-stage renal failure. 878 74


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