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)

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 mechanisms whereby growth hormone may increase renal plasma flow (RPF) and GFR are not known, but circumstantial evidence has implicated insulin-like growth factor I (IGF-I) as a mediator of this effect. This study examined whether an infusion of IGF-I will increase RPF and GFR, whether this effect occurs quickly, and if this effect is dependent on eicosanoids or peptide hormones known to affect renal function. Rats fasted for 3 d to reduce IGF-I and IGF-I plasma binding proteins were anesthetized; then the rats received an intravenous injection of 25 micrograms/kg IGF-I, and an infusion of 25 micrograms/kg IGF-I within 20 min. Controls received infusion of the vehicle. RPF (para-aminohippurate clearances), GFR (inulin clearances), renal vascular resistance (RVR), mean arterial blood pressure (MABP), plasma IGF-I, and glucose concentrations were measured repeatedly. At the end of the 20-min infusion, plasma IGF-I tended to be increased in the animals that received IGF-I (P = 0.069), but did not increase in the control rats. IGF-I induced a significant and sustained fall in RVR and rise in RPF and GFR without any change in MABP. A small, transient, but significant decrease in plasma glucose concentrations was observed during IGF-I but not during vehicle infusion. Indomethacin, but not somatostatin, blocked the renal response to IGF-I infusion. Thus, IGF-I infusion increases RPF and GFR and reduces RVR in fasted rats. This effect requires the presence of eicosanoids but does not seem to require other peptide hormones suppressed by somatostatin.
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PMID:Evidence that insulin-like growth factor I increases renal plasma flow and glomerular filtration rate in fasted rats. 291 Sep 16

Hyperfiltration is a very characteristic feature in insulin-dependent diabetes. Hyperfiltration is to some extent associated with long-term glycemic control but the correlation is not very strong. Long-term hyperfiltration may play a role in the genesis of late diabetic nephropathy, but it is difficult to distinguish effects of hyperfiltration per se from effects of poor metabolic control. Long-term hyperfiltration without diabetes does not produce nephropathy. It is hypothesized that IDDM patients who do not show considerable hyperfiltration in spite of poor metabolic control may be those who are to some extent protected against late diabetic nephropathy, but other mechanisms may also be involved in the renal protection of these patients, who survive long-term diabetes without nephropathy. On the other hand, those with poor metabolic control combined with hyperfiltration are likely to develop nephropathy. In addition, it is suggested that the metabolic aberrations in diabetes, with the subsequent changes in the biochemistry of the glomerular wall, are permissive and absolutely required for the development of diabetic nephropathy. Of note, diabetic glomerulopathy in NIDDM occurs without significant hyperfiltration and extreme hyperfiltration in the one-kidney-model (without diabetes) does not produce nephropathy. Nonglycemic modalities of intervention, resulting in reduced hyperfiltration, e.g., low-protein diet or administration of somatostatin analogues, deserves interest as new potential ways of preventing or postponing diabetic nephropathy. Also intervention with aldose-reductase inhibitors may be an important therapeutic modality for those patients in whom good metabolic control is not obtainable. It is now well-established that antihypertensive treatment, including ACE-inhibition, reduces rate of decline in GFR in patients with already established nephropathy. In addition, protein excretion is diminished in IDDM patients with incipient diabetic nephropathy by antihypertensive treatment where GFR is well-preserved during treatment. No data are available for NIDDM.
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PMID:Comparative renal pathophysiology relevant to IDDM and NIDDM patients. 306 56

Our results as well as those in the literature suggest that some hormone or combination of hormones, that are inhibited by somatostatin, is responsible for the hyperfiltration response following amino acid infusion/protein ingestion. Recently, we have infused amino acids with somatostatin and replaced the stimulated levels of insulin/glucagon/growth hormone observed during amino acid infusion alone (Castellino and DeFronzo, preliminary results). This combined hormone replacement was able to overcome the inhibitory effect of somatostatin and return the increase in RPF and GFR to the elevated levels observed following amino acid infusion. These results suggest that some combination of these hormones is involved in the hyperfiltration response to hyperaminoacidemia. However, several comments are worthy of emphasis. First, somatostatin is known to inhibit a number of hormones (Table 1), and a contributory role for any of these should not be excluded. Second, a large body of evidence has accumulated to indicate that neither insulin, glucagon, nor growth hormone alone are capable of augmenting either RPF or GFR. The possibility that infusion of the three hormones together will increase RPF and GFR, when neither hormone alone will do so, has not been examined. More likely, some interaction between the elevated plasma amino acid concentrations and the elevated hormone levels is responsible for the hyperfiltration response. It is interesting to speculate that such an interaction might be exerted at the level of the kidney by an effect on renal amino acid metabolism.
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PMID:Regulation of renal hemodynamics by plasma amino acid and hormone concentrations. 332 9

To evaluate the dynamics of GH-secretion after infusion of growth hormone releasing factor, human pancreatic growth hormone releasing factor (hpGRF1-44) was infused over 2 and 5 h at a dosage of 100 micrograms hpGRF1-44/h into 11 healthy subjects. The infusion was started and terminated with a 50 micrograms hpGRF1-44 bolus injection. In 5 subjects 200 micrograms TRH was given 4 h after starting the infusion. In addition, 4 healthy subjects received 50 micrograms hpGRF1-44 bolus injection every 2 h. GRF, somatostatin, GH, Prl, and TSH were measured by radioimmunoassay. The initial 50 micrograms GRF bolus increased GH-levels in all 11 subjects with a maximum at 30 min (24.1 +/- 5.1 ng/ml +/- SE). However, though hpGRF1-44 was continuously infused and GFR-levels remained elevated, GH decreased to a minimum 270 min after start of infusion (2.6 +/- 0.6 ng/ml). The GH-response to the second bolus at the end of the infusion was lower compared to the first response (14.6 +/- 3.4 ng/ml after 2 h and 7.6 +/- 2.5 ng/ml after 5 h). TRH did not lead to a GH-increase during hpGRF1-44 infusion though Prl and TSH rose normally. The intermittent bolus injection of 50 micrograms hpGRF1-44 led to continuously decreasing GH-responses to the same GRF-dosage (I. bolus: 16.5 +/- 1.6 ng/ml; II. bolus: 4.2 +/- 0.8 ng/ml; III. bolus: 3.4 +/- 0.5 ng/ml). No change in somatostatin levels was observed. These findings show that GRF infusion or bolus injection in short intervals does not sustain elevated GH-levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone releasing factor infusion does not sustain elevated GH-levels in normal subjects. 644 Mar 92

The effects of somatostatin (ST) on the regulation of the glomerular filtration rate have not been extensively studied. The present experiments were designed to analyze this possible relationship. ST alone did not modify the planar cell surface area (PCSA) of cultured rat mesangial cells (CRMC), but it prevented and reversed the reduction in PCSA induced by 10 nM angiotensin II (Ang II) in a dose- and time-dependent manner. ST (1 microM) completely prevented and reversed the increase in the myosin light chain phosphorylation induced by 10 nM Ang II. Incubation with pertussis toxin (PT, 0.5 micrograms/ml) inhibited the effect of ST on the Ang II-dependent changes in PCSA, but this effect was not inhibited by the blockade of the vasodilatory prostaglandins (indomethacin, 10 microM) or nitric oxide (L-N-methyl-arginine, 0.2 mM) synthesis. 2',5'-dideoxyadenosine (DDA, 0.1 mM), an adenylate cyclase blocker, and methylene blue (MB, 30 microM), a soluble guanylate cyclase blocker, did not interfere with the ST inhibitory effect on the Ang II-dependent reduction in PCSA of rat mesangial cells. ST also blocked the reduction in PCSA induced by phorbol myristate acetate (PMA, 300 nM). ST was also able to prevent and revert the Ang II dependent reduction in glomerular cross-sectional area of isolated rat glomeruli, also in a dose- and time-dependent fashion. Finally, intravenous administration of ST (200 ng/kg body wt as a bolus plus a continuous injection of 25 ng/min/kg body wt) partially blocked the reduction in GFR (measured as CIn) and RPF (measured as CPAH) and the increase in filtration fraction induced by the intravenous administration of Ang II (1.7 micrograms/min/kg body wt) in anesthetized rats. In summary, these results suggest that ST could antagonize the renal actions of Ang II, increasing the GFR and RPF decreased by Ang II, and this effect could be dependent, at least partially, on a direct relaxing effect of ST on mesangial cells.
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PMID:Somatostatin antagonizes angiotensin II effects on mesangial cell contraction and glomerular filtration. 809 76

It was previously demonstrated that initial kidney hypertrophy has been seen in diabetic animals and somatostatin infusion suppresses GFR and serum insulin like growth factor (IGF-1) in diabetic patients. I studied the effects of somatostatin analogue (octreotide) on glomerular hypertrophy in diabetic rats. The animals were randomized into six groups: two groups of streptozocin (STZ) induced diabetic, insulin-treated diabetic and non-diabetic rat groups. One of these three groups were treated with two daily subcutaneous injections of octreotide (10 micrograms x 2) for a period of five weeks. In diabetic rats, body weight, blood sugar, glucose excretion, serum insulin, urinary volume, urinary protein, serum creatinine or creatinine clearance did not differ in diabetic rats with vs. without octreotide injection, but kidney weight (2.97 +/- 0.12 vs. 3.28 +/- 0.08 mg, P < 0.05; mean +/- SEM) and estimated glomerular volume (9.13 +/- 0.22 vs. 12.77 +/- 0.34 x 10(5) microns 3, P < 0.001) were all reduced in diabetic rats with octreotide when compared with untreated diabetic rats. In non-diabetic rats, octreotide reduced body weight (340.3 +/- 6.5 vs. 367.1 +/- 3.8g, P < 0.01) and kidney weight (2.29 +/- 0.08 vs. 2.51 +/- 0.04 g, P < 0.05) when compared with non-diabetic rats without octreotide. Urinary protein excretion (8.57 +/- 1.39 vs. 14.29 +/- 1.53 mg/day, P < 0.05), serum 1GF-1 concentration (956.3 +/- 180.7 vs. 1546.1 +/- 88.1 mg/day, P < 0.05) and estimated glomerular volume (7.69 +/- 0.16 vs. 9.72 +/- 0.15 x 10(5) microns 3, P < 0.001) significantly differed in insulin treated diabetic rats with vs. without octreotide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Octreotide suppresses the kidney weight and glomerular hypertrophy in diabetic rats]. 850 54

There are no proven, effective therapies for polycystic kidney disease (PKD) or polycystic liver disease (PLD). We enrolled 42 patients with severe PLD resulting from autosomal dominant PKD (ADPKD) or autosomal dominant PLD (ADPLD) in a randomized, double-blind, placebo-controlled trial of octreotide, a long-acting somatostatin analogue. We randomly assigned 42 patients in a 2:1 ratio to octreotide LAR depot (up to 40 mg every 28+/-5 days) or placebo for 1 year. The primary end point was percent change in liver volume from baseline to 1 year, measured by MRI. Secondary end points were changes in total kidney volume, GFR, quality of life, safety, vital signs, and clinical laboratory tests. Thirty-four patients had ADPKD, and eight had ADPLD. Liver volume decreased by 4.95%+/-6.77% in the octreotide group but remained practically unchanged (+0.92%+/-8.33%) in the placebo group (P=0.048). Among patients with ADPKD, total kidney volume remained practically unchanged (+0.25%+/-7.53%) in the octreotide group but increased by 8.61%+/-10.07% in the placebo group (P=0.045). Changes in GFR were similar in both groups. Octreotide was well tolerated; treated individuals reported an improved perception of bodily pain and physical activity. In summary, octreotide slowed the progressive increase in liver volume and total kidney volume, improved health perception among patients with PLD, and had an acceptable side effect profile.
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PMID:Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. 2069 Jan 98

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by recalcitrant hypophosphatemia. Reports from the Indian subcontinent are scarce, with most being single center experiences involving few patients. Herein, we conducted a retrospective analysis of 30 patients of TIO diagnosed at three tertiary care hospitals in India. Patients with persistent hypophosphatemia (despite correction of hypovitaminosis D), normocalcemia, elevated alkaline phosphatase, low TmP/GFR and elevated or 'inappropriately normal' FGF23 levels were labeled as having TIO. They were sequentially subjected to functional followed by anatomical imaging. Patients with a well-localized tumor underwent excision; others were put on phosphorous and calcitriol supplementation. The mean age at presentation was 39.6 years with female:male ratio of 3:2. Bone pain (83.3%) and proximal myopathy (70%) were the chief complaints; 40% of cases had fractures. The mean delay in diagnosis was 3.8 years. Tumors were clinically detectable in four patients (13.3%). The mean serum phosphate was 0.50 mmol/L with a median serum FGF23 level of 518 RU/mL. Somatostatin receptor-based scintigraphy was found to be superior to FDG-PET in tumor localization. Lower extremities were the most common site of the tumor (72%). Tumor size was positively correlated with serum FGF23 levels. Twenty-two patients underwent tumor resection and 16 of them had phosphaturic mesenchymal tumors. Surgical excision led to cure in 72.7% of patients whereas disease persistence and disease recurrence were seen in 18.2% and 9.1% of cases, respectively. At the last follow-up, serum phosphate in the surgically treated group was significantly higher than in the medically managed group.
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PMID:Tumor-induced osteomalacia: experience from three tertiary care centers in India. 3072 71