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)

Hormonal and glycemic changes in 22 rhesus monkeys were characterized during the first days after treatment with streptozotocin (STZ) (45 to 55 mg/kg, administered intravenously [IV]). Almost half (10/22) of the monkeys developed insulin-dependent diabetes mellitus (STZ-IDDM) within five days following injection. Four of the remaining monkeys did not become insulin dependent for at least 6 months after STZ treatment, during which time they were considered non-insulin-dependent, and eight monkeys never required exogenous insulin. In the STZ-IDDM group, plasma immunoreactive c-peptide (IRC-P) levels fell by three hours after STZ from a mean +/- SEM of 252 +/- 82 to 101 +/- 45 pg/mL, as glucose and immunoreactive glucagon (IRG) levels increased from 65 +/- 3 and 120 +/- 37, respectively, to 336 +/- 43 mg/dL and 234 +/- 52 pg/mL, respectively. Between six and 30 hours after treatment, IRC-P increased to a peak of 1,561 +/- 360 pg/mL before falling permanently to less than 60 pg/mL by 66 hours. During this period, glucose and IRG responded in a reciprocal fashion by falling and then increasing to levels above 300 mg/dL and 300 pg/mL, respectively, by 66 hours. In the non-insulin-dependent diabetes mellitus (STZ-NIDDM) group, no clear reciprocal relationship between IRC-P and glucose and IRG was obtained. In nine additional monkeys subjected to total pancreatectomy (Px), IRC-P and IRG levels fell immediately and permanently by greater than 90% and 75%, respectively. Levels of immunoreactive somatostatin increased steadily over the initial 96 hours following STZ, but did so both STZ-IDDM and Px monkey groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical changes in rhesus monkey during the first days after streptozotocin administration are indicative of selective beta cell destruction. 296 84

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

An insulin-producing cell line, Clone-16, of hamster origin, was characterized for islet hormone production and for reactivity with islet cell surface (ICSA) and islet cell cytoplasmic (ICA) antibodies in sera from children with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM). The Clone-16 cells have a doubling time of about 50-60 hr. The cells produced 63 +/- 3 ng (mean +/- SD) immunoreactive insulin and 9.4 +/- 0.3 ng immunoreactive glucagon per day per 10(6) cells, while somatostatin (SRIF) and pancreatic polypeptide (PP) were undetectable. The reactivity with autoantibodies in IDDM sera was assessed by indirect immunofluorescence or 125I-protein A binding assay on intact cells to detect islet cell surface antibodies (ICSA) or on frozen sections of cell pellets to detect islet cell cytoplasmic antibodies (ICCA) by indirect immunofluorescence. Although the proportion of the ICSA-positive Clone-16 cells compared favorably with rat islet cells (r = 0.81; p less than 0.01), we found 5/10 IDDM sera to be positive on rat islet cells but 8/10 on the Clone-16 cells. There was also a good correlation in the 125I-protein A binding assay between mouse islet cells and Clone-16 cells (r = 0.91; p less than 0.01). Frozen sections of Clone-16 cells showed a cytoplasmic immunofluorescence in 8/10 of the IDDM sera and this reaction parallelled the results obtained in the standard indirect immunofluorescence assay with a frozen section of human blood group O pancreas. We conclude that the insulin- and glucagon-producing Clone-16 cells are a useful cell line for detecting islet cell autoantibodies.
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PMID:Detection of islet cell autoantibodies in newly diagnosed diabetic patients using insulin-producing Syrian hamster cells. 330 Nov 57

To elucidate the mechanism by which somatostatin lowers blood glucose concentration and insulin requirement following carbohydrate ingestion in insulin dependent diabetic patients (IDDM; n = 6), the amount of insulin required for the assimilation of a 50 g glucose load was determined by means of an automated glucose-controlled insulin infusion system with and without concomitant somatostatin infusion. During the 3 hour period following glucose loading plasma concentrations of glucagon and growth hormone were diminished by somatostatin, as were the rise in blood glucose and insulin requirement (4.0 +/- 1.2 U) when compared with the control study (11.3 +/- 1.5 U; p less than 0.01). With cessation of somatostatin blood glucose levels and insulin requirement rose during the following 2 hour observation period (7.5 +/- 1.2 U) but remained basal during the control study (0.7 +/- 0.6 U; p less than 0.0005). Thus the integrated amounts of insulin required for glucose hormone were temporarily suppressed by somatostatin. It is concluded that the diminished insulin requirement and delayed rise in blood glucose during somatostatin administration after an oral glucose load is not due to its "antidiabetic" action by suppressing glucagon and growth hormone release. Our findings favour inhibition of intestinal carbohydrate absorption as the determining cause for the "antidiabetic" action of somatostatin.
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PMID:Antidiabetic action of somatostatin after oral glucose loading: due to suppression of glucagon and growth hormone or of intestinal carbohydrate absorption? 611 14

The application of immunofluorescence technique with anti-insulin, anti-glucagon, anti-somatostatin, and anti-pancreatic polypeptide (PP) antisera to sections of precisely sampled regions of the human pancreas allowed the quantitative evaluation of the total content of these four endocrine cell populations in 13 nondiabetics, in 2 insulin-dependent diabetics (IDDM), and in 2 non-insulin-dependent diabetic subjects (NIDDM) of various age and sex. In nondiabetic subjects, PP-cells appear sex-related. Male individuals have a significantly greater volume of PP-cells than female. In diabetic subjects, the only marked difference as compared with nondiabetics is the reduction of insulin cell volume in IDDM. Other small differences between individual endocrine cell volumes are detectable in both IDDM and NIDDM as compared with nondiabetics, but their significance is at present unclear. The qualitative changes of islet structure accompanying insulin cell reduction in IDDM were not considered in the present study.
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PMID:Quantitation of endocrine cell content in the pancreas of nondiabetic and diabetic humans. 613 Oct 2

Addition of diet fiber to meals is reported to result in significant reduction of postprandial glucose levels in diabetic patients as well as in normal subjects. In the present study effect of guar intake (12 g) on plasma somatostatin-like immunoreactivity (SRIF-LI) was studied in non-insulin dependent diabetes (NIDDM) and in insulin-dependent diabetes (IDDM) to see if somatostatin plays a role in reducing postprandial glucose. In 6 of 7 normal controls plasma SRIF-LI increased and reached a maximum at 30 min after guar intake. In 5 of 7 NIDDM patients SRIF-LI reached a maximum at 90 min after guar intake, while in five IDDM patients SRIF-LI significantly decreased through 120 min after guar intake. These results suggest the possibility that guar induced somatostatin secretion contributes to reduction of postprandial glucose levels at least in NIDDM patients as well as in normal subjects, for somatostatin is reported to inhibit glucose uptake from gastrointestinal tract.
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PMID:Effect of guar intake on plasma somatostatin-like immunoreactivity in diabetic patients. 613 60

In an attempt to rest the beta cells of newly diagnosed children with type I diabetes mellitus (IDDM) and thus possibly preserve beta cell function, ten children were given Octreotide, a somatostatin analog, for the first 21 days after diagnosis. Ten age-matched diabetic children served as controls. Although there were no differences in either insulin requirements or in hemoglobin A1 levels, there were significant increases in the glucagon-stimulated C-peptide levels of the experimental group at six and 12 months after diagnosis, compared to control patients.
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PMID:A randomized trial of a somatostatin analog for preserving beta cell function in children with insulin dependent diabetes mellitus. 773 71

Prophylactic insulin therapy prevents IDDM in spontaneous animal models of the disease and has shown promise in preventing the disease in humans. Although large clinical trials have been formed to use this therapy, a comparative analysis of the efficiency of different pharmaceutical forms and doses of insulin in preventing IDDM has not been performed, and the mechanism underlying the observed prevention of disease is unknown. In the NOD-scid/scid adoptive transfer model of IDDM (10(7) new-onset NOD splenocytes injected intravenously into 6- to 8-week NOD/scid-scid recipients; insulitis develops at 6-9 days post-transfer and 100% IDDM by 32 days post-transfer), life-table (log-rank) analyses revealed that IDDM can be delayed (compared with insulin-free diluent, once daily, n = 8) with equivalent efficiency by prophylactic administration (-9-50 days post-transfer) of high (metabolism-altering) doses of short-acting (0.5 U, once daily, regular, n = 13) or long-acting (0.5 U, once daily, ultralente, n = 9) insulin as well as non-metabolism-altering low-dose insulin (0.02 U, once daily, regular, n = 8). Furthermore, IDDM was delayed with somatostatin (0.2 microgram, twice daily, n = 11), an agent that suppresses endogenous insulin production. No significant difference was seen between the preventative effects of these agents. In an assessment of when therapies can be initiated and still maintain clinical efficiency, only prophylactic somatostatin therapy delayed IDDM (n = 10, P = 0.02) when initiated at 14 days post-transfer, whereas the short-acting insulin regimen did not retard the onset of IDDM (n = 8, P = 0.25) compared with diluent-treated controls. The 24-h urinary C-peptide levels were significantly reduced with short-acting (-56%, P = 0.01) and long-acting (-67%, P = 0.02) insulin products and somatostatin (-59%, P = 0.02) compared with diluent-treated controls. These results indicate that both immunological and metabolic (i.e., beta-cell rest) factors may contribute to the beneficial effects of prophylactic insulin therapy.
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PMID:Immunological and metabolic effects of prophylactic insulin therapy in the NOD-scid/scid adoptive transfer model of IDDM. 854 66

To examine the effect of the somatostatin analog, octreotide, on insulin-mediated glucose uptake, seven insulin-dependent diabetic (IDDM) subjects were studied with and without 4 days of continuous subcutaneous octreotide administration (1 mg/kg/d). Insulin dosage was adjusted after frequent measurements of plasma glucose level. On the third day a hormonal and metabolic blood profile was obtained, and on the fourth day a euglycemic (5 mmol/L), hyperinsulinemic (1 mU/kg/min) clamp was performed in combination with calorimetry and a muscle biopsy. Mean plasma glucose levels on day 3 were similar (7.9 +/- 0.9 v 9.0 +/- 0.6 mmol/L). Growth hormone (GH) (0.39 +/- 0.10 v 0.78 +/- 0.23 mg/L, P < .05), insulin-like growth factor-1 (IGF-1) (127 +/- 17 v 157 +/- 21 mg/L, P < .05), and nonesterified fatty acids (NEFA) (239 +/- 25 v 405 +/- 44 mmol/L, P < .01) were lower following octreotide administration. Insulin requirements were reduced during octreotide administration, resulting in significantly lower insulin levels (27.3 +/- 2.7 v 39.9 +/- 9.9 mU/L, P < .5). During the clamp, glucose and insulin levels wer similar. Following octreotide, glucose disposal (7.33 +/- 0.49 v 6.08 +/- 0.55 mg/kg/min, P < .05) increased and hepatic glucose production (HGP) was more suppressed (-1.56 +/- 0.07 v -0.63 +/- 0.34 mg/kg/min, P < .05, 220 to 270 minutes). Oxidative glucose disposal (indirect calorimetry) was enhanced (3.09 +/- 0.24 v 2.70 +/- 0.37 mg/kg/min, P = .08), whereas glucose storage, as well as the fractional velocity for glycogen synthase activity, were unaltered during octreotide administration. Conversely, octreotide decreased lipid oxidation (0.12 +/- 0.1 v 0.41 +/- 0.15 mg/kg/min, P < .05). In conclusion, a low-dose octrotide infusion for 4 days to IDDM subjects leads to significantly increased insulin sensitivity.
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PMID:Effects of the somatostatin analog, octreotide, on glucose metabolism and insulin sensitivity in insulin-dependent diabetes mellitus. 859 92

Random peptide libraries (RPLs) screening with IDDM sera has identified 5 disease-specific 'mimotopes' displayed on phage (phagotopes). We characterised one phagotope (CH1p), by raising a rabbit antibody against the peptide insert on phage, which was employed in immunohistochemistry, Western blotting and cDNA libraries screening. The CH1p mimotope was detected in somatostatin cells of human islets and experimentally raised anti-osteopontin antibodies or human sera positive for the phagotope, detected a similar subpopulation of islet cells. The screening of cDNA library identified a clone corresponding to human osteopontin. In summary, RPLs proved to be successful in the identification of a novel islet-related autoantigen (osteopontin), whose significance in disease remains to be established.
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PMID:Osteopontin is an autoantigen of the somatostatin cells in human islets: identification by screening random peptide libraries with sera of patients with insulin-dependent diabetes mellitus. 1050 61


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