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)

Indirect data exist which implicate elevated growth hormone (GH) as a factor in the development of diabetic nephropathy. The administration of somatostatin (SRIH) has been shown to reverse many of the changes found in early diabetic nephropathy; however, it is unknown whether SRIH causes these effects by the suppression of GH or by other unspecified factors. To study directly the possible effect of excess GH in the development of diabetic nephropathy, either ovine growth hormone (0.2 mg oGH) or diluent buffer was administered IM daily for 19 weeks to diabetic rats and to controls. Severity of nephropathy was assessed by 24 hour urine albumin excretion (UAE), relative kidney weight, and kidney histology. Results showed that diabetic rats overall had elevated UAE and kidney weight vs non-diabetic rats (46.2 +/- 8.6 vs 5.4 +/- 1.3 mg per day and 5.7 +/- 0.2 vs 2.7 +/- 0.1 mg per g of body weight, respectively, p < 0.001). However, no differences were detected between diabetic rats treated with GH compared to control diabetic rats. Additionally, diabetic rats had histopathologic changes consistent with early diabetic nephropathy, but no difference in severity scores was found between diabetic groups. These data provide evidence against GH as an etiologic factor in the development of diabetic nephropathy and it is speculated by the authors that SRIH exerts its protective renal effects in diabetes by mechanisms other than GH suppression.
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PMID:Effect of chronic growth hormone administration on diabetic nephropathy in the rat. 829 1

Glomerular hyperfiltration is a characteristic feature of acromegaly but it is uncertain whether albuminuria is elevated in this disease. To investigate the role of abnormal growth hormone (GH) and insulin-like growth factor I (IGF-I) levels on urinary protein excretion, we measured the overnight urinary albumin excretion rate (UalbV) and creatinine clearance in 14 acromegalic patients with metabolically active disease (fasting GH > 5 micrograms/l and IGF-I > 2.2 kU/l), 8 GH-deficient patients and 20 control subjects. The UalbV was higher in the acromegalic patients (median 8.4 (range 4.2-68.2) micrograms/min) than in the GH-deficient patients (2.0 (0.9-5.9) micrograms/min, p < 0.001) and control subjects (3.3 (1.0-7.8) micrograms/min, p < 0.01). Five acromegalic patients had UalbV levels above the normal upper normal limit of 10 micrograms/min. Only one patient with concomitant untreated hypertension had persistent microalbuminuria. Creatinine clearance also was higher in the acromegalic patients (p < 0.05) and lower in the GH-deficient patients (p < 0.05) than in the control subjects. In 11 of these acromegalic cases, the lowering of GH by 63% and of IGF-I by 48%, following treatment with the somatostatin analogue (N = 10) or spontaneous pituitary infarction (N = 1), reduced the UalbV by 29% to 4.9 (3.1-45.2) micrograms/min (p < 0.01). Among the acromegalic patients (25 observations), the UalbV was related to GH (r = 0.61, p < 0.01), IGF-I (r = 0.57, p < 0.01) and creatinine clearance (r = 0.54, p < 0.01). In conclusion, circulatory GH and IGF-I levels influence albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of growth hormone and insulin-like growth factor I on urinary albumin excretion: studies in acromegaly and growth hormone deficiency. 837

To challenge the view that resistance to insulin-mediated glucose uptake in noninsulin-dependent diabetes mellitus (NIDDM) is limited to patients with microalbuminuria, high blood pressure, or obesity, we compared measurements of insulin resistance in 29 normal volunteers and 31 normotensive patients with NIDDM (mean +/- SE fasting plasma glucose, 160 +/- 10 mg/dL). The patients with NIDDM were nonobese (body mass index, < 27 kg/m2), with urinary albumin excretion (UAE) less than 20 micrograms/min on the basis of two overnight urine collections. The two groups were similar in age and body mass index. Although patients with NIDDM had neither high blood pressure nor microalbuminuria; both their blood pressure (125 +/- 2/79 +/- 1 vs, 113 - 2/73 +/- 2 mm Hg) and UAE excretion (4.7 +/- 0.58 vs. 2.12 +/- 0.17 micrograms/min) were somewhat higher than those in the control population. Resistance to insulin-mediated glucose disposal was quantified by measurement of the steady state plasma glucose (SSPG) and insulin (SSPI) concentrations during the last 30 min of an 180-min infusion of somatostatin (5 micrograms/min), insulin (25 mU/min-m2), and glucose (240 mg/min-m2). The results showed that SSPI concentrations were similar in the two groups (64 +/- 3 vs. 62 +/- 3 microU/mL), but SSPG concentrations were approximately twice as high in patients with NIDDM (258 +/- 15 vs. 139 +/- 11 mg/dL;P < 0.001); demonstrating the presence of severe insulin resistance. Furthermore, the magnitude of the differences in the SSPG values of the two groups did not change and remained highly significant when adjusted for small differences in age, body mass index, blood pressure, and UAE. Finally, SSPG did not correlate with age, body mass index, blood pressure, or UAE in either group. These data again demonstrate that insulin resistance exists in patients with NIDDM, and that this defect is present in the absence of obesity, high blood pressure, or microalbuminuria.
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PMID:Resistance to insulin-mediated glucose disposal in patients with noninsulin-dependent diabetes mellitus in the absence of obesity or microalbuminuria--a Clinical Research Center study. 877 92

The study was performed to determine the relationship between urinary albumin excretion (UAE) and resistance to insulin-mediated glucose disposal in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty-five non-obese male patients were enrolled; UAE rates were determined on two 24-hour urine collections, and resistance to insulin-mediated glucose disposal was quantified by measurement of steady-state plasma glucose (SSPG) and steady-state plasma insulin concentrations during the last 30 minutes of a 180-minute infusion of somatostatin, insulin, and glucose. Twenty-four-hour urine UAE rates varied from 6 to 112 microgram/min, and microalbuminuria (> 20 microgram/min) was present in seven of 25 patients. SSPG concentration ranged from 158 to 419 mg/dL, and there was no relationship between UAE rates and SSPG concentration (r = .16, P = NS). Furthermore, the mean SSPG concentration was not significantly different in seven patients with microalbuminuria compared with 18 normoalbuminuric subjects (318 +/- 20 v 298 +/- 17 mg/dL). Thus, resistance to insulin-mediated glucose disposal occurs in patients with NIDDM in the absence of microalbuminuria, and we could not detect any relationship between UAE and insulin resistance in this population.
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PMID:Lack of a relationship between urinary albumin excretion rate and insulin resistance in patients with non-insulin-dependent diabetes mellitus. 878 Dec 91

A 59-year-old man presented with painful subcutaneous nodules on the anterior surfaces of the legs. He had received oral antibiotics and supportive care for presumed cellulitis and thrombophlebitis, but had minimal improvement. Five months earlier, he had undergone pancreaticoduodenectomy for acinar pancreatic carcinoma; at that time, the serum level of amylase had been normal, but the level of lipase was elevated. The patient denied fever, rigors, arthritis/arthralgia, or pleuritic pain. His medications included aspirin, furosemide, ranitidine, and nortriptyline. He denied any allergies. Physical examination revealed numerous firm, tender, erythematous and violaceous, subcutaneous nodules on the lower extremities, with marked bilateral pitting edema (Fig. 1). Skin biopsy of a representative lesion revealed septal panniculitis, consistent with erythema nodosum (Fig. 2). None of the characteristic changes of pancreatic fat necrosis was present. The patient was treated with aspirin, 650 mg orally, q 6 h, and indomethacin, 50 mg orally, q 12 h, but he continued to develop new nodules; prednisone, 60 mg orally was begun. Although he reported improvement in symptoms, the nodules failed to respond clinically and older nodules ulcerated along the medical aspect of the right leg (Fig. 3). The complete blood count was normal, except for hemoglobin, 10.9 mg per dL. Routine serum biochemical studies were also normal, except for albumin, 3.1 mg per dL, LDH, 312 U per L, and SGOT, 51 U per L. Serum amylase was 14 U per L (normal per 30 to 115 U per L) and serum lipase was 54,160 U per L (normal 0 to 200 U per L). Chest roentgenogram and tuberculin skin test were negative. A CT scan of the abdomen revealed extensive liver metastases. A second biopsy of the skin and subcutis of a necrotic nodule revealed lobular panniculitis with the characteristic picture seen in pancreatic fat necrosis (Fig. 4). The patient was presumed to have metastatic pancreatic carcinoma and pancreatic fat necrosis. Nodules subsequently developed on the thighs, arms, hands, wrists, and fingers. He developed arthritis and arthralgias of the ankles, wrists, and hands, bilaterally, and the right knee. Aspiration of a right knee effusion revealed numerous neutrophils, but no evidence of infection. Treatment was begun with the somatostatin analog, octreotide, in increasing doses. During this therapy, the lesions did not progress and new lesions did not appear. There was no change in the lipase level. Inadvertently, octreotide was omitted at discharge, but reintroduction of octreotide was associated with lack of further progression of the nodules, according to the patient's spouse; however the patient became progressively debilitated and his abdominal pain worsened, requiring continuous sedation. His condition deteriorated and he died several weeks after hospital discharge.
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PMID:Fat necrosis with features of erythema nodosum in a patient with metastatic pancreatic carcinoma. 883 28

This study was initiated to see if the presence of resistance to insulin-mediated glucose disposal, glucose intolerance, and hyperinsulinemia in healthy patients with hypertension was dependent upon the coexistence of microalbuminuria. For this purpose we compared these variables in 68 individuals: 34 patients with hypertension and 34 normal volunteers. The two groups were similar in terms of age, gender distribution, body mass index, and ratio of waist to hip girth. Furthermore, although four patients with hypertension satisfied the criteria for microalbuminuria, as compared to one normal volunteer, the urinary albumin excretion (UAE) rates were similar in the two groups (8.07 +/- 1.08 v 7.67 +/- 1.12 micrograms/min). Despite the similarities, both the plasma glucose and insulin responses to a 75 g oral glucose challenge were significantly higher (P < .01) in those with high blood pressure. In addition, the steady-state plasma glucose (SSPG) concentrations at the end of a 180 min continuous infusion of somatostatin, insulin, and glucose was significantly higher in those with hypertension (156 +/- 13 v 107 +/- 10 mg/dL, P < .01). Since the steady-state plasma insulin levels were also somewhat higher in those with hypertension, the higher SSPG values indicate that these individuals were relatively insulin resistant as compared to the control population. Finally, UAE rates were not correlated with either the plasma glucose or insulin responses to oral glucose or to the SSPG concentrations--either in the entire group of 68, or when the 34 patients in each group were considered separately. These results demonstrate that insulin resistance, glucose intolerance, and hyperinsulinemia can occur independently of microalbuminuria in patients with hypertension.
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PMID:Insulin resistance in patients with essential hypertension can occur in the absence of microalbuminuria. 889 47

D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) is a cyclic, penicillamine-containing octapeptide that is structurally similar to somatostatin and displays greater antagonist potency and selectivity for mu-opioid receptors, compared with the classical mu-selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2. The aim of this study was to determine whether CTAP can enter the central nervous system (CNS) by crossing either the blood-brain barrier or the blood-cerebrospinal fluid barrier (CSF) and to characterize the mechanism of CNS entry. CNS entry of [3H]CTAP was compared with that of the vascular space marker [14C]inulin and the mu-agonist [3H]morphine. By using an in situ brain perfusion technique coupled to high-performance liquid chromatographic analysis, greater amounts of radioactivity were detected in the brain or CSF at most time points for [3H]CTAP, compared with [14C]inulin. [3H]CTAP was found to remain predominantly intact in the brain after a 20-min rat brain perfusion (62.8%). CTAP was also stable in the blood and serum of rats (T1/2 > 500 min), showing that the structure of this peptide offers enzymatic resistance. Additionally, [3H]CTAP was found to be extensively protein-bound to albumin in the perfusion medium (68.2%) and to proteins in rat serum (84.2%). Entry into the brain and CSF was not inhibited by the addition of unlabeled CTAP to the perfusion medium, suggesting that passage into the CNS is most likely through diffusion across the membranes that comprise the blood-brain barrier, rather than by saturable transport. Also, greater amounts of [3H]morphine entered both the brain and CSF after a 20-min brain perfusion, compared with [3H]CTAP. The increased CNS penetration observed for [3H]morphine, compared with [3H]CTAP, is likely due to the increased lipophilicity of morphine, as shown by its higher octanol/saline partition coefficient. Based on the pharmacokinetic profile, CTAP may be a promising mu-selective antagonist that can be used as a treatment for opiate overdose or addiction and also as a pharmacological tool to further understand opioid neurobiology.
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PMID:Blood-brain barrier permeability and bioavailability of a highly potent and mu-selective opioid receptor antagonist, CTAP: comparison with morphine. 899 21

The ability of the liver to regenerate following resection is remarkable. However, there is evidence to suggest that tumour growth within the regenerating liver is significantly increased. As octreotide (a synthetic analogue of somatostatin) inhibits the growth and development of hepatic tumour in rats, we have investigated its effects on liver regeneration, liver blood flow, hepatic reticuloendothelial system activity and tumour growth in the rat following partial hepatectomy (PH). Octreotide significantly inhibited liver regeneration in the rat 1 and 2 weeks following PH when compared with controls (regeneration index: 1.0 and 1.14 cf. 1.14 and 1.4, respectively). There was no significant difference in hepatic arterial or portal venous blood flow following PH in control or octreotide-treated rats. However, portal pressure was significantly reduced in octreotide-treated rats. Hepatic reticuloendothelial system activity was significantly increased in octreotide-treated rats compared with control animals 1 and 2 weeks after hepatectomy (uptake of radiolabelled technetium-99m albumin colloid: 2.2 and 3.9 cf. 1.6 and 1.9). The growth of both HSN (fibrosarcoma) and K12-Tr (colonic adenocarcinoma) cells in the regenerating liver was significantly decreased by octreotide treatment compared with controls (median percentage hepatic replacement: HSN control 71.3%, Octreotide 8.4%, K12-Tr Control 38.3%, Octreotide 4.5%). The results of the present study demonstrate that octreotide inhibits both liver regeneration and tumour growth following PH, possibly via a similar mechanism.
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PMID:Effects of octreotide on liver regeneration and tumour growth in the regenerating liver. 907 22

Renal and glomerular growth is inherent in early human and experimental diabetes frequently followed by later increase in urinary albumin excretion (UAE). Treatment with angiotensin converting enzyme (ACE) inhibitors has proven effective in delaying progression of human and experimental diabetic renal changes, and so has somatostatin analog treatment in experimental diabetes. The aim of the present study was to investigate three weeks of octreotide and captopril treatment alone or in combination following three months of untreated experimental diabetes, and compare the effects to those of insulin treatment. Diabetes induced significant increases in renal and glomerular growth and urinary albumin excretion. Octreotide and captopril alone and in combination reduced renal but not glomerular size, and the combined administration reduced UAE. None of these schedules affected blood glucose levels. Insulin treatment inducing euglycemia significantly reduced renal and glomerular size and UAE. In conclusion, insulin treatment with normalization of the diabetic metabolic derangement nearly normalizes renal and glomerular growth and UAE after three months of untreated diabetes. The combined treatment of octreotide and captopril was also followed by a significant decrease in renal growth and reduction in UAE compared to placebo treatment without affecting the metabolic control of the diabetic animals.
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PMID:Effect of octreotide, captopril or insulin on renal changes and UAE in long-term experimental diabetes. 945 15

Octreotide is a long-acting somatostatin analog that has been shown to have various effects in diabetes. This study was performed to evaluate whether octreotide affects the vascular complications of diabetes mellitus. Albuminuria and serum thrombomodulin were used as markers of vascular and renal dysfunction. We studied the effect of octreotide in 27 patients with insulin-dependent diabetes mellitus (IDDM). They received 200 microg octreotide per day over a period of 6 months. As a marker of endothelial cell damage, we measured the serum thrombomodulin level. We also measured urinary albumin excretion, hemoglobin A1c (HbA1c), insulin-like growth factor-1 (IGF-1), and other parameters. IGF-1 decreased from 123 ng/mL before treatment to 114 ng/mL after 6 months of octreotide treatment (P = .009), while no significant change was observed in the unblinded control group (from 103 ng/mL to 102 ng/mL after 6 months of treatment). Urinary albumin excretion in patients with macroalbuminuria declined from 1,124 mg/L before octreotide treatment to 556 mg/L after 6 months of treatment (P < .05), whereas no change was observed in the control group. There was also a reduction of the plasma thrombomodulin level from 61.8 ng/mL to 46.1 ng/mL (P < .07) after 6 months of treatment. Furthermore, HbA1c decreased from 8.75% +/- 1.27% to 8.12% +/- 1.23% (P < .07) after octreotide treatment.
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PMID:Octreotide (somatostatin analog) treatment reduces endothelial cell dysfunction in patients with diabetes mellitus. 1053 84


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