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)

The aim of the present study was to characterize the role of glucagon in countering the prolonged hypoglycemia resulting from insulin infusion and to determine whether its effect is manifest through glycogenolysis and/or gluconeogenesis. Two groups of 18-h fasted somatostatin-treated dogs were given intraportal insulin at 5 mU.kg-1.min-1. In one group (SimGGN; n = 6), glucagon was infused intraportally so as to mimic the normal response to hypoglycemia. In a second group (BasGGN; n = 6), glucagon was infused at a basal rate. Glucose turnover and gluconeogenesis were assessed by combining tracer and hepatic balance techniques. Exogenous glucose was infused as needed to maintain equivalent hypoglycemia at approximately 45 mg/dl in the two groups. Although glucagon concentrations were significantly different, the levels of other counterregulatory hormones were equivalent in both experimental protocols. Endogenous glucose production (EGP) in SimGGN doubled from 2.4 +/- 0.2 to 5.4 +/- 0.8 mg.kg-1.min-1 by 1 h before dropping to 4.5 +/- 0.2 mg.kg-1.min-1 in the 3rd h of insulin infusion. EGP in BasGGN was initially 2.5 +/- 0.1 mg.kg-1.min-1, unchanged by 1 h, and increased to 3.9 +/- 0.2 mg.kg-1.min-1 by the 3rd h of insulin infusion. In the 1st h of insulin infusion, the rise in gluconeogenesis in both groups was equal and represented only a small part of total EGP. By the 3rd h, gluconeogenesis was the major contributor to total EGP, and gluconeogenic efficiency increased significantly more in SimGGN than BasGGN (261 vs. 140%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of glucagon in countering hypoglycemia induced by insulin infusion in dogs. 176 38

A 35-year-old Type 1 diabetic man with severe disabling postural hypotension was studied for physiological abnormalities, precipitating factors, and effect of current treatment. A 24-h blood pressure profile indicated a diurnal variation in systolic blood pressure with the lowest values recorded between 0100 and 0600 h, during which the patient often lost consciousness on standing (mean standing systolic pressure 78 mmHg at night vs 105 mmHg in the afternoon, p less than 0.001). Food induced a profound fall in systolic pressure, both while supine and while standing erect. The systolic pressure fall during euglycaemia was 49 mmHg vs 3 mmHg during hypoglycaemia. Plasma noradrenaline and adrenaline levels were low during euglycaemia, but increased during hypoglycaemia. Therapeutic manoeuvres aimed at increasing heart rate (by atrial tachypacing) and reducing the peripheral pooling of blood (vasoconstricting drugs and gravity suit), together with the somatostatin analogue octreotide, proved ineffective. These observations demonstrate the phenomenon of post-prandial exacerbation of postural hypotension in a Type 1 diabetic patient, and indicate that despite failure of conventional methods of treatment, hypoglycaemia increased plasma catecholamines and was effective in abolishing the blood pressure fall on standing.
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PMID:Disabling postural hypotension complicating diabetic autonomic neuropathy. 183 15

Growth hormone-releasing hormone (GHRH) stimulates GH secretion in man and the hormonal response is specific. The attenuation of GH response to bolus GHRH after prior exposure of GHRH of up to 24 h was not demonstrated in normal or GH-deficient subjects after more prolonged exposure. This suggests that the partial loss of responsiveness to GHRH may reflect short-term negative feedback by GH. The stimulatory effect of clonidine and L-dopa on GH release is mediated via GHRH. Other stimuli like hypoglycaemia, arginine and propranolol augment GH release in man by modulating hypothalamic somatostatin secretion. Although GHRH test can differentiate between hypothalamic or pituitary cause of GH deficiency, it is of little diagnostic value in children with short stature. Favourable results have been observed in 60-70% of GH-deficient children treated with GHRH, but the dose and mode of administration are still being explored. We found that low dose (1-2 micrograms/kg) GHRH given subcutaneously every 3 h by a pump was effective in promoting growth in 5 of 7 patients after 1 year. Treatment was continued for 2-4 years in 4 patients and growth velocities ranging from 4.5 to 8.2 cm/year were maintained using a dose of 3 micrograms/kg/pulse.
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PMID:Growth hormone-releasing hormone: clinical studies and therapeutic aspects. 190 90

Cholinergic pathways play an important role in the regulation of GH secretion. To assess their participation in GH feedback, we investigated the effect of pyridostigmine (an acetylcholinesterase inhibitor) on plasma GH responses to GH-releasing hormone (GHRH) plus TRH, insulin hypoglycemia, and arginine as well as on the inhibition of these responses by exogenous GH. The GH response to each stimulus was inhibited by an infusion of GH (0.55 micrograms/m2/min), started 4 h earlier. Pyridostigmine (120 mg, orally), administered 30 min before the stimulus, enhanced GH responses to GHRH and insulin during both saline and GH infusions. However, GH responses during combined administration of pyridostigmine and GH were less than those during pyridostigmine alone. GH responses to arginine, in contrast, were not affected by pyridostigmine in either the absence or presence of exogenous GH. TSH responses to TRH were unaltered by either GH or pyridostigmine. Pyridostigmine enhancement of GH responses to a maximally stimulatory dose of GHRH suggests that its effect is exerted by inhibition of somatostatin release. The lack of effect of pyridostigmine on plasma GH responses to arginine suggests that arginine and pyridostigmine increase GH secretion through a common pathway. The enhancement by pyridostigmine of GH responses in both the presence and absence of exogenous GH suggests that exogenous GH and pyridostigmine exert their discordant effects on GH secretion through independent mechanisms.
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PMID:The role of the cholinergic pathway in growth hormone feedback. 190 84

Hypoglycemia with hyperinsulinism persisted in a newborn weighing 6410 g despite treatment with high doses of diazoxide and glucagon, as well as infusions of glucose and somatostatin. A subtotal pancreatectomy was performed after nesidioblastosis had been diagnosed on the basis of the laboratory findings. Due to the persistence of therapy-resistant hypoglycemia, a total pancreatectomy preserving the duodenum and the bile duct was done 6 weeks later. With insulin and pancreatic enzyme substitution the now 6-year, 9-month-old child has shown normal, age, appropriate development.
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PMID:Total pancreatectomy in a case of nesidioblastosis due to persisting hyperinsulinism following subtotal pancreatectomy. 190 2

Hypoglycaemia is a frequent finding during the neonatal period and may be due to insulin overproduction. Patients with Beckwith-Wiedemann syndrome have reduced numbers of somatostatin-producing cells and decreased extractable somatostatin. In this study the effect of long-acting somatostatin (SMS201-995) on the glucose and insulin levels in an infant with Beckwith-Wiedemann syndrome and hyperinsulinaemic non-ketotic hypoglycaemia is described. SMS201-995 lowered basal insulin levels while maintaining normal glucose and insulin homeostasis. During fasting however, both glucose levels declined rapidly whereas insulin levels did not. The absence of both ketosis and elevated levels of free fatty acids and lactate during hypoglycaemia, as observed in our patient, are important diagnostic clues since the insulin levels themselves may sometimes be only slightly elevated.
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PMID:The effects of a somatostatin analogue on the metabolism of an infant with Beckwith-Wiedemann syndrome and hyperinsulinaemic hypoglycaemia. 191 15

To examine the glucoregulatory responses to stress and their impact on diabetes, we used the following models of stress: A) Hypoglycemia; B) Epinephrine infusion; C) intracerebroventricular (ICV) injection of carbachol, an analog of acetylcholine. A) Hypoglycemia induces release of all counterregulatory hormones. During acute hypoglycemia, glucose production increases initially mainly due to glucagon release but eventually also due to a very large increment in catecholamines. In newborn dogs, neither epinephrine nor glucagon respond to a decrease in plasma glucose. This lack of a safeguard against hypoglycemia may indicate that the brain in pups is less dependent on a normal supply of glucose as a fuel, than in adult dogs. Counterregulation is enhanced when the effects of endogenous opiates are blocked by naloxone, indicating that endogenous opiates play a regulatory role during hypoglycemia. However, beta-endorphins which can be released with epinephrine during various stress situations, potentiate the peripheral effect of epinephrine. Glucoregulatory responses, even to slight changes in plasma glucose, are greatly enhanced during glucocorticoid treatment. This apparently reflects the greater sensitivity of the liver to glucagon. In diabetic dogs, similar to human diabetics, the glucagon response is abolished and the response of the catecholamines is partially decreased. On the basis of histological studies, we proposed that the deficient glucagon response in diabetes could be related to an increase in the somatostatin-glucagon ratio in the diabetic pancreas. This ratio is further augmented when normoglycemia is maintained with insulin. In response to a decrease in plasma glucose, there is a biphasic increment in glucose production in normal dogs, which is missing in diabetes. When normoglycemia is restored in diabetic dogs with phlorizin treatment, the second but not the first increment in glucose production is restored. We postulated, therefore, that the toxic effect of hyperglycemia, in addition to the lack of glucagon response, is the main reason why in diabetes, glucose production cannot respond promptly to a decrease in plasma glucose. The low rate of metabolic clearance of glucose seen in diabetes in the post-absorptive state, also reflects, at least in part, the toxic effect of glucose, because with acute normalization of glucose with phlorizin, metabolic glucose clearance substantially improves. Hyperglycemia is the main reason for the decreased number of glucose transporters in diabetic muscle. B) Epinephrine infusion in normal dogs mimics some effects of stress, in that it increases glucose production, inhibits metabolic glucose clearance and increases lipolysis. These metabolic effects of epinephrine are independent of glucagon release.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of stress on glucoregulation in physiology and diabetes. 192 81

The role of extrarenal potassium homeostasis is well recognized as a major mechanism for the acute defense against the development of hyperkalemia. The purpose of this report is to examine whether or not the various mechanisms of extrarenal potassium regulation are intact in patients with end-stage renal disease (ESRD). The available data suggest that with the development of ESRD and the uremic syndrome there is impaired extrarenal potassium metabolism that is related to a defect in the Na,K-adenosine triphosphatase (ATPase). The responsiveness of uremic patients to the various effector systems that regulate extrarenal potassium handling is discussed. Insulin is well positioned to play an important role in the regulation of plasma potassium concentration in patients with impaired renal function. The role of basal insulin may be even more important than previously appreciated, since somatostatin infusion causes a much greater increase in the fasting plasma potassium in rats with renal failure than in controls. Furthermore, stimulation of endogenous insulin by oral glucose results in a greater intracellular translocation of potassium in uremic rats than in controls. Under at least two common physiologic circumstances, feeding and vigorous exercise, endogenous catecholamines might also act to defend against acute increments in extracellular potassium concentration. However, it is important to appreciate that the response to beta 2-adrenoreceptor-mediated internal potassium disposal is heterogeneous as judged by the variable responses to epinephrine infusion. Based on the evidence presented in this report, a regimen for the treatment of life-threatening hyperkalemia is outlined. Interpretation of the available data demonstrate that bicarbonate should not be relied on as the sole initial treatment for severe hyperkalemia, since the magnitude of the effect of bicarbonate on potassium is variable and may be delayed. The initial treatment for life-threatening hyperkalemia should always include insulin plus glucose, as the hypokalemic response to insulin is both prompt and predictable. Combined treatment with beta 2-agonists and insulin is also effective and may help prevent insulin-induced hypoglycemia.
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PMID:Extrarenal potassium tolerance in chronic renal failure: implications for the treatment of acute hyperkalemia. 156 35

Octreotide acetate is a long-acting analogue of the naturally occurring inhibitory gastrointestinal peptide, somatostatin. We tested the efficacy of octreotide in controlling the symptoms of dumping syndrome in response to a provocative meal in a randomized, double-blinded, crossover trial in nine severely affected patients. Pretreatment with octreotide acetate (100 micrograms injected subcutaneously) reduced postprandial dumping symptoms from a mean +/- SEM score of 15.7 +/- 1.6 (placebo treatment day) to 4.6 +/- 1.7. With placebo treatment, all nine patients became symptomatic in response to the meal, whereas with octreotide treatment, symptoms occurred in only two of nine patients. Similarly, all placebo-treated patients showed a postprandial increase in pulse rate to a mean +/- SEM of 105 +/- 6 beats per minute, whereas only one of nine octreotide-treated patients showed an increase in pulse rate (mean +/- SEM, 80 +/- 3 beats per minute). These differences were also statistically significant. While no significant changes were observed in postprandial hematocrit values or osmolality between placebo and octreotide treatments, octreotide prevented hypoglycemia in four affected patients and significantly inhibited insulin release. We conclude that octreotide is a useful tool in the treatment of patients with severe, refractory dumping syndrome.
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PMID:Control of dumping symptoms by somatostatin analogue in patients after gastric surgery. 192 23

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


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