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)

Patients with type 1 diabetes mellitus (IDDM) show augmented GH secretion, which is implicated in the pathogenesis of microvascular complications. On the other hand, it is well known that beta-adrenergic receptors have inhibitory influence on GH secretion, likely via stimulation of hypothalamic somatostatin. Since the possibility of pharmacological suppression of GH secretion would be of value in IDDM, we investigated the effect of salbutamol (SAL, 4 mg orally at -60 min) on the GH response to GHRH (1 micrograms/kg iv at 0 min) in 6 well-controlled (mean HbA1c +/- SEM: 7.3 +/- 0.5%) patients with IDDM. Salbutamol was able to inhibit basal GH levels (p < 0.05) as well as to abolish the GHRH-induced GH rise. After SAL administration, a significant (p < 0.05) reduction of glucagon levels was also found. Our data show that the enhancement of beta 2 adrenergic activity by oral therapeutical doses of SAL inhibits basal and GHRH-stimulated GH secretion in patients with IDDM.
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PMID:Inhibition by salbutamol of GHRH-induced GH release in type 1 diabetes mellitus. 133 41

This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. Understanding this precise regulation requires sensitive isotope dilution methods that can measure the rates at which glucose is produced by the liver and used by the tissues on a minute-to-minute basis. Validation studies indicated that the non-steady-state tracer method yields reasonable results when the specific activity of plasma glucose does not change abruptly. During hyperinsulinemic glucose clamps, the decrease in specific activity of glucose can be prevented by the MSTI. During exercise, the decrease of specific activity can be only in part ameliorated by step-tracer infusion. Depancreatized dogs are used extensively as a model of selective insulin deficiency, because dog stomach secretes physiological amounts of glucagon. This strategy can avoid injections of somatostatin, which can have other affects in addition to the suppression of insulin and glucagon. In human diabetes, in addition to an increase of glucose production, there is also an increase in glucose cycling in the liver. In animal models of diabetes, mild NIDDM, and in glucose intolerance, the percentage of increments of glucose cycling are much larger than those of glucose production. We hypothesize, therefore, that measurements of glucose cycling can be used as an early marker of glucose intolerance. Application of different tracer strategies and use of the depancreatized dog as a model of diabetes, we investigated the importance of the indirect effects of insulin in the pathogenesis of diabetes. 1) Because, in the treatment of IDDM, insulin is administered by the peripheral routes we compared the relative importance of hepatic and peripheral effects of insulin in regulating the rate of glucose production. Experiments were performed in depancreatized dogs that were initially maintained at moderate hyperglycemia (10 mM) with subbasal portal insulin infusion. During the experimental period, insulin was infused either peripherally or portally at 0.9 mU.kg-1.min-1. In addition, peripheral infusions were also given at 0.45 mU.kg-1.min-1. We concluded that when suprabasal insulin levels are provided to moderately hyperglycemic depancreatized dogs, the suppression of glucose production is more dependent on peripheral than portal insulin concentrations. This indirect effect of insulin may be mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and/or by suppressive effect of insulin on glucagon secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Banting Lecture: glucose turnover. A key to understanding the pathogenesis of diabetes (indirect effects of insulin). 149 70

A decline in plasma insulin and an increase in glucagon are known to occur during intense and/or prolonged exercise. However, it is not established whether changes in insulin and glucagon secretion are involved in the precise matching of hepatic glucose production to the enhanced glucose uptake by muscle during brief, low intensity exercise. We studied the effects of 30-min cycle exercise at 40% of maximal aerobic capacity in healthy subjects and C-peptide-deficient subjects with type 1 diabetes (IDDM) using [3-3H]glucose to estimate glucose turnover. Diabetic subjects were studied during continuous iv insulin infusion, which normalized glucose kinetics before experimental perturbations. In control (saline-infused) experiments, endogenous glucose appearance (Ra) increased by 80-90% above baseline to match the increase in glucose disappearance in both normal and IDDM subjects, even though the latter exercised at fixed levels of plasma free insulin, averaging 203 +/- 19 pmol/L. In other experiments, somatostatin was infused, and glucagon (1.0 ng/kg.min) and insulin (at two different rates) were maintained at constant levels. Infusion of insulin in normal subjects at doses sufficient to maintain constant peripheral plasma insulin was associated with no apparent effect on glucose turnover (plasma insulin, 80 +/- 21 pmol/L, compared to 52 +/- 5 pmol/L during saline; P = NS). However, insulin infusion at doses that normalized the portal insulin concentration (approximately 208 pmol/L) together with glucagon replacement inhibited the rise in glucose production in both normal and IDDM subjects. There were similar 45-55% reductions (P less than 0.03) of the increase in Ra seen with exercise in control experiments. When peripheral plasma free insulin (and presumably portal levels as well) were increased by about 20% in this experimental setting in IDDM (278 +/- 43 pmol/L), the suppression of Ra was even more profound, and Ra failed to increase at all with exercise. We conclude that the hormonal regulation of Ra in brief duration exercise in man does not necessitate the decrements in portal venous insulin observed under more intense exercise conditions as long as an exercise-induced glucagon secretory response can occur. Glucagon secretion alone cannot prevent hypoglycemia when portal venous insulin concentrations are increased by minimal amounts, such as in insulin-treated diabetics.
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PMID:Islet hormonal regulation of glucose turnover during exercise in type 1 diabetes. 196 78

A deceased 59-year-old woman with insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis was autopsied. She had had diabetes mellitus since she was 30 years old, and insulin therapy was started at 34 years. Laboratory findings were as follows: s-GOT 85, s-GPT 31, gamma-globulin 2.45 g/dl. Immunological tests were positive for anti-smooth muscle antibody and anti-ENA antibody with high titers of antithyroglobulin and anti-microsome antibodies. HLA analysis revealed the presence of DR-4. The thyroid biopsy specimen showed microscopic features characteristic of chronic thyroiditis at 52 years of age. She had been repeatedly admitted for the control of diabetes mellitus. She was admitted for the 9th time in June, 1987 following complaints of abdominal pain. After admission, her general condition became gradually worse, and she died of peritonitis in September, 1987. Pathological examination of the liver revealed an expansion of fibrous tissue on Glisson's capsule accompanied by lymphocytic infiltration and was diagnosed to be chronic inactive hepatitis. As for the thyroid gland, fibrous tissue replaced an extensive area of the thyroid gland, and normal thyroid tissue was not observed. Lymphocytic infiltration was less in comparison with that in the previous biopsy. As for the pancreas, atrophy of exocrine pancreatic tissue and fibrous change in interstitial tissue was observed. Lymphocytic infiltration was also seen in the interstitial exocrine tissue but not in the islet. Immunohistochemical examination of the islets using anti-insulin, glucagon and somatostatin antibodies by ABC peroxidase method showed the selective disappearance of B cells in the islets. The pathological changes in the thyroid gland, liver and pancreas suggest that autoimmune mechanism may be involved in the pathogenesis of chronic thyroiditis, chronic hepatitis and IDDM with exocrine pancreatic impairment in this case.
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PMID:[An autopsied case of insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis]. 259 7

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

We studied the effects of a premeal sc injection of an analog of somatostatin (SMS 201-995, Sandoz) on the postprandial glycemic excursions, insulin requirement and hormone profiles (GH, glucagon and C-peptide) in 8 IDDM patients (diabetes duration 14.0 +/- 6.5 yr, daily insulin requirement 36 +/- 6.4 U) maintained normoglycemic by connecting them to a closed-loop insulin infusion system (Betalike, Genoa). The morning of the test the patients were connected to the Betalike and their glucose levels stabilized for at least 4 h. At 13:00 h the study was begun with a sc injection of 50 micrograms of SMS 201-995 or placebo (randomly) and a standardized mixed meal (800 Kcal) was given. Blood samples were obtained 0, 15, 30, 60, 120 and 180 min after the injection. Each patient was tested both with SMS 201-995 and placebo. Postmeal glycemic peaks were decreased after SMS 201-995 (119.6 +/- 5.4 mg/dl vs 149.1 +/- 4.2; p less than 0.05) as well as insulin requirements (3.2 +/- 0.8 U vs 13.3 +/- 1.9; p less than 0.01) for the 180 min postprandial period. Similarly, glucagon level was reduced 30 min postprandially (24 +/- 6 pg/ml vs 59 +/- 24; p less than 0.05) and so GH level only 180 min after lunch (p less than 0.05). The premeal injection of SMS decreases postprandial glycemic excursions and the corresponding insulin requirement. The action of SMS 201-995 may be mainly mediated by the suppression of postprandial glucagon peak.
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PMID:Effects of a somatostatin derivative (SMS 201-995) on postprandial hyperglycemia in insulin-dependent diabetics studied by means of a closed-loop device. 267 Nov 12

The glucagon response to insulin hypoglycaemia is frequently reduced in patients with IDDM. In the present study arginine infusion, thought to act directly on the islet cells, was used to stimulate somatostatin (SRIF) and glucagon in IDDM without residual B-cell function. Thirteen IDDM patients' were compared with 13 sex- and age matched normal controls following an arginine infusion. The plasma SRIF concentrations in the 'IDDM group' and normal controls increased from 24.2 +/- 2.5 to 31.1 +/- 3.9 pmol/l (P less than 0.01) and 19.7 +/- 1.7 to 23.9 +/- 3.4 pmol/l respectively after 10 min (P less than 0.01). The plasma glucagon concentrations increased from 27 +/- 4.7 to 176 +/- 23.1 pmol/l (P less than 0.01) and 36 +/- 5.0 to 302 +/- 31.9 pmol/l (P less than 0.01) respectively after 20 min. Thus, in long standing IDDM without residual B-cell function, increased plasma SRIF concentrations are found and the glucagon response to arginine is reduced. The last observation further explains why these patients are especially vulnerable to hypoglycaemia.
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PMID:Increased peripheral venous somatostatin concentration and decreased glucagon response to arginine in patients with insulin dependent diabetes mellitus without residual B-cell function. Increased plasma SRIF in IDDM. 286 13

The effect of a new octapeptide analogue of somatostatin (SMS 201-995) on blood glucose and gut hormone levels was studied in 10 C-peptide-negative, insulin-dependent diabetic (IDDM) subjects. On separate days, either 50 or 100 micrograms SMS or placebo was s.c. injected simultaneously with an identical insulin dose 30 min before a mixed meal. Postprandial blood glucose decreased after 100 micrograms SMS s.c. within 30 min from 8.9 +/- 0.7 to 7.8 +/- 0.6 mmol/L (P less than 0.001) and remained at similar levels during 180 min. In contrast, postprandial blood glucose concentration increased after placebo from 9.9 +/- 0.8 to 13.8 +/- 0.9 mmol/L (SMS versus placebo P less than 0.001). Plasma glucagon decreased rapidly after SMS to the limit of detection (P less than 0.001) and remained lowered during 180 min; in contrast, glucagon levels increased after the meal during the placebo study (SMS versus placebo P less than 0.001). Plasma growth hormone concentrations were significantly lower after SMS than after placebo (P less than 0.05). SMS abolished completely the postprandial increase in plasma gastrin and pancreatic polypeptide (PP) concentrations. Plasma free fatty acid (FFA) and triglyceride concentrations decreased after SMS, reaching significantly lower levels than after placebo (P less than 0.05 and P less than 0.01), respectively). Plasma SMS concentration increased rapidly after s.c. administration of SMS; its appearance preceded that of plasma free insulin after s.c. insulin injection. Fifty micrograms SMS was similarly effective as 100 micrograms in decreasing blood glucose, triglycerides, glucagon, and gut hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced postprandial hyperglycemia after subcutaneous injection of a somatostatin-analogue (SMS 201-995) in insulin-dependent diabetes mellitus. 286 93

To further study the elevated plasma somatostatin (SRIF)--and reduced plasma glucagon concentrations found in IDDM patients without residual B-cell function compared to normal controls, we investigated 39 such patients, randomly assigned to three different insulin treatment regimens; conventional therapy with two injections a day (CTh), insulin pump (CSII) and multiple injections (MI), for 1 year. They were given an arginine infusion (0.5 g/kg/20 min). The mean basal plasma SRIF values in the CTh, CSII and MI groups were 20.8 +/- 3.3, 18.6 +/- 1.8 and 20.6 +/- 2.8 pmol/l and the mean basal plasma glucagon values were 30 +/- 5.7, 19 +/- 2.3 and 27 +/- 4.7 pmol/l, respectively. Both SRIF and glucagon increased in all groups in relation to arginine infusion. For both hormones, the mean values were highest in the CTh group, lowest in the CSII group, although the differences were not significant. The mean HbA1 values for the last 3 months within the test were 10.0 +/- 0.5, 8.8 +/- 0.3 and 9.1 +/- 0.5%, respectively, in the same order as above. The CTh group had significantly higher HbA1 values than the CSII group (p less than 0.02). We conclude that small differences in long-term blood glucose control are of inconsiderable importance for the islet hormonal response to arginine found in IDDM without B-cell function.
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PMID:Plasma somatostatin and plasma glucagon in long-term IDDM without residual B-cell function. No effect of different long-term metabolic control. 287 90

Altogether 54 male patients with insulin-dependent diabetes mellitus participated in the studies. The impact of insulin-induced hypoglycemia on posthypoglycemic insulin sensitivity was evaluated for up to 12 hours following nadir hypoglycemia. The effect on glucose homeostasis following transient elevation of counterregulatory hormones was studied by exogenous administration of adrenaline, adreno-corticotropic hormone and growth hormone and by suppression of the endogenous release of growth hormone in connection with hypoglycemia. The studies were performed in the fasting state preceded by a 24 hour intravenous insulin infusion in order to avoid interference of subcutaneous insulin. Insulin resistance was determined by a constant rate intravenous infusion of somatostatin, insulin and glucose. This test seemed appropriate for the evaluation of total insulin resistance, and its reproducibility was acceptable. By using this method it was demonstrated that insulin resistance occurred for at least 12 hours after a hypoglycemic event in patients with IDDM, and that adrenaline caused immediate insulin resistance which, however, faded out within four to six hours, while GH exerted no immediate effect on insulin sensitivity but caused marked and sustained insulin resistance after a lag period of about four hours. Cortisol had no apparent effect within six hours but enhanced the effect of GH. The magnitude of these diabetogenic effects of hypoglycemia and GH was less pronounced in patients who already were more insulin resistant. These results are compatible with the idea that adrenaline is of major importance for the counterregulation and restoration of blood glucose during the first few hours following hypoglycemia, while GH is responsible for the induction of a long-lasting state of insulin resistance. It is possible that such prolonged insulin resistance may cause posthypoglycemic hyperglycemia in patients with IDDM. These studies therefore indicate that the GH suppressing hormone somatostatin may be of clinical value as an adjunct to insulin in the treatment of patients with insulin-dependent diabetes mellitus and labile blood glucose control.
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PMID:Studies on posthypoglycemic insulin resistance in insulin-dependent diabetes mellitus. 290 16


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