Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:034761 (insulin)
 211,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NSILA-s (nonsuppressible insulin-like activity, soluble in acid ethanol) is a serum peptide that has insulin-like and growth-promoting activities. We have demonstrated previously that liver plasma membranes possess separate receptors for NSILA-s and insulin and have characterized the insulin receptor in detail. In the present study we have characterized the properties and specificity of the NSILA-s receptor and compared them to those of the insulin receptor in the same tissue. Both 125I-NSILA-s and 125I-insulin bind rapidly and reversibly to their receptors in liver membranes; maximal NSILA-s binding occurs at 20 degrees while maximal insulin binding is seen at 1-4 degrees. The pH optimum for NSILA-s binding is broad (6.0 to 8.0), in contrast to the very sharp pH optimum (7.5 to 8.0) for insulin binding. Both receptors exhibit a high degree of specificity. With the insulin receptor, NSILA-s and insulin analogues compete for binding in proportion to their insulin-like potency: insulin greater than proinsulin greater than NSILA-s. With the NSILA-s receptor, NSILA-s is most potent and the order is reversed: NSILA-s greater than proinsulin greater than insulin. Furthermore, six preparations of NSILA-s which varied 70-fold in biological activity competed for 125I-NSILA-s binding in order of their potencies. NSILA-s which had been inactivated biologically by reduction and aminoethylation and growth hormone were less than 1/100,000 as potent as the most purified NSILA-s preparation. Purified preparations of fibroblast growth factor, epidermal growth factor, nerve growth factor, and somatomedins B and C were less than 1% as effective as NSILA-s in competing for the 125I-NSILA-s suggesting that these factors act through other receptors. In contrast, somatomedin A was 10% as active as NSILA-s and multiplication-stimulating activity was fully as active as NSILA-s in competing for the NSILA-s receptor. Analysis of the data suggests that there are approximately 50 times more insulin receptors than NSILA-s receptors per liver cell, while the apparent affinity of NSILA-s receptors is somewhat higher than that of the insulin receptor.
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PMID:The NSILA-s receptor in liver plasma membranes. Characterization and comparison with the insulin receptor. 0 Mar 91

Sequential determinations of glucose outflow and inflow, and rates of gluconeogenesis from alanine, before, during and after insulin-induced hypoglycemia were obtained in relation to alterations in circulating epinephrine, norepinephrine, glucagon, cortisol, and growth hormone in six normal subjects. Insulin decreased the mean (+/-SEM) plasma glucose from 89+/-3 to 39+/-2 mg/dl 25 min after injection, but this decline ceased despite serum insulin levels of 153+/-22 mul/ml. Before insulin, glucose inflow and outflow were constant averaging 125.3+/-7.1 mg/kg per h. 15 min after insulin, mean glucose outflow increased threefold, but then decreased at 25 min, reaching a rate 15% less than the preinsulin rate. Glucose inflow decreased 80% 15 min after insulin, but increased at 25 min, reaching a maximum of twice the basal rate. Gluconeogenesis from alanine decreased 68% 15 min after insulin, but returned to preinsulin rates at 25 min, and remained constant for the next 25 min, after which it increased linearly. A fourfold increase in mean plasma epinephrine was found 20 min after insulin, with maximal levels 50 times basal. Plasma norepinephrine concentrations first increased significantly at 25 min after insulin, whereas significantly increased levels of cortisol and glucagon occurred at 30 min, and growth hormone at 40 min after insulin. Thus, insulin-induced hypoglycemia in man results from both a decrease in glucose production and an increase in glucose utilization. Accelerated glycogenolysis produced much of the initial, posthypoglycemic increment in glucose production. The contribution of glycogenolysis decreased with time, while that of gluconeogenesis from alanine increased. Of the hormones studied, only the increments in plasma catecholamines preceded or coincided with the measured increase in glucose production after hypoglycemia. It therefore seems probable that adrenergic mechanisms play a major role in the initiation of counter-regulatory responses to insulin-induced hypoglycemia in man.
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PMID:The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man. 0 91

The vicinity of several hormone-producing glands as part of the anatomy of the intestinal tract and the resulting interaction has been confirmed by the discovery of hormonal factors of a specifically gastro-intestinal origin. Today we are mainly interested in the interaction between intermediary metabolism and incretory intestinal function; this is characterized by the joint action of conventional glandular hormones such as insulin and pancreatic glucagon as well as by the incretion of diffuse intestinal organs, hormones such as secretin, pancreozymin, motilin, VIP and GIP. The latter are at present subject of active research with the object of discovering their physiological significance be it as tissue hormones or as humoral agents with a "long distance" impact; their role within pathophysiology is also of interest. GIP ("gastric inhibitory peptide"), apart form acting upon the intestinal tract, also causes a marked rise in insulin production; this GIP possibly is the factor responsible for the difference in glucose tolerance following i. v. or oral administration of glucose, something that scientists have been trying to discover for a long time. We have also endeavored to investigate somatostatin. This substance was originally discovered as a hypothalamic factor with inhibitory action on growth hormone secretion; in the meantime, however, cells containing and possibly also producing somatostatin have also been detected in the intestine and particularly in the islets of Langerhans (D-cells). Since somatostatin inhibits insulin secretion and especially glucagon release as well as the exretory functions of the stomach and of the pancreas, the significance of this hormone possibly is that of a tissue hormone with inhibitory action on adjacent cells. As factor inhibiting both endocrine and exocrine secretory processes it would combine these two complexes. The possible therapeutic significance of somatostatin administration to diabetics would lie in the saving of insulin. A third sector of present-day research deals with the interaction between the calcium metabolism and the hormones involved as well as the intestine. We know that patients suffering from primary hyperparathyroidism are prone to contract stomach ulcers and pancreatitis; patients with a gastrinoma and a hyperfunction of the epithelial bodies suffer from a Zollinger-Ellison-sindrome and this again suggests association with endocrine polyadenomatosis (Wermer syndrome). The inhibitory action of the parathormone antagonist calcitonin on the exocrine functions of the intestinal tract, such as the acid secretion of the stomach and the enzyme secretion of the pancreas, have already given rise to some considerations and experiments relative to treatment. It is to be hoped that because of all the joint observations cited above there will be better intergration of research both from the aspect of gastro-enterology and endocrinology. This might hopefully elucidate some of the unresolved problems ranging from basic research to practical application.
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PMID:[Interaction between gastrointestinal hormones and endocrine regulation]. 0 83

The binding of 125I-labelled human growth hormone to the 100000g microsomal membrane fraction prepared from the livers of normal female rats was dependent on time, temperature, pH, membrane concentration and concentration of 125I-labelled human growth hormone. At 22 degrees C binding reached a steady state after 16h, with the mean maximal specific binding being 20% of the tracer initially added. Dissociation of 125I-labelled human growth hormone from the membranes, after addition of excess of unlabelled hormone, was relatively slow with a half-time greater than 24h. Only minor degradation of the 125I-labelled human growth hormone was observed during incubation with membranes for 16 or 25h at 22 degrees C. Similarly, no significant change in the ability of membranes to bind human growth hormone was evident after preincubation of the membranes for 16 or 25h. Specificity studies showed that up to 90% of the 125I-labelled human growth hormone bound could be displaced by 1 mug of unlabelled hormone. Ovine prolactin also showed considerable competition for the binding site. Non-primate growth-hormone preparations (ovine, bovine, porcine and rat) and non-related hormones (insulin, thyrotropin, lutropin and follitropin) all showed negligible competition. Scatchard analysis of the binding data was consistent with two classes of binding site with binding affinities of 0.64 X 10(10) +/- 0.2 X 10(10)M-1 and 0.03 X 10(10) +/- 0.007 X 10(10)M-1 and corresponding binding capacities of 98.4 +/- 10 fmol/mg of protein and 314.6 +/- 46.3 fmol/mg of protein. These studies provide data which, in general, are consistent with the criteria required for hormone-receptor interaction. However, proof of the thesis that the human-growth-hormone-binding sites in female rat liver represent physiological receptors must await the demonstration of a correlation between hormone binding and a biological response.
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PMID:Characterization of the binding of human growth hormone to microsomal membranes from rat liver. 0 79

The binding of biologically active [125I]thyrotropin to purified plasma membranes prepared from bovine thyroid glands was studied. At 4 degrees C, specific binding reached a maximum after 2 h of incubation and a plateau was maintained for up to 20 h. Degradation of [125I]thyrotropin was undetectable after 2 h of incubation and was only 10% of the total after 20 h. At pH 6.0, at which binding was maximal, a single class of binding sites, having a dissociation constant of approx. 25 nM, was evident. Dissociation studies revealed first order kinetics with a half-time of 2-3 min. At pH 7.5, binding curves were complex, suggesting two orders of binding sites with dissociation constants of approx. 200 nM and 80 pM. Further, at this pH, dissociation of the thyrotropin from its receptor was also complex, suggesting the presence of two first order reactions, one with a half-time similar to that seen at pH 6.0 and another with a half-time of 4 h. At both pH 6.0 and 7.5, insulin, glucagon, growth hormone, and prolactin were without effect on [125I]thyrotropin binding. Similar high affinity and low affinity binding sites were seen with porcine thyroid membranes, but only low affinity sites were seen with either rat liver membranes or human cultured lymphocytes.
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PMID:The interaction of radioiodinated thyrotropin with plasma membranes. Evidence for high affinity binding sites in the thyroid. 0 55

After a brief historical account, the physiological effect of glucocorticoid hormones are analysed. Their main point of impact is neoglucogenesis from proteins. To this is added their direct action on carbohydrates, their intervention in the use of lipids, and in the movement of water and salts. Cortisone penetrates into the cell, is fixed by a cortisone receptor in order to be transferred into the nucleus and to act on the transformation of ADN-ARN. Its relationships with cyclic AMP are discussed. The hormonal correlations of glucocorticoids are numerous. (insulin, catecholamine, glucagon, growth hormone, androgen). Synthetic cordicoids have biological actions which are close to those of glucocorticoids, but vary depending on their structure. These physiological and pharmacological notions imply certain precautions in the use of this type of hormone derivative.
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PMID:[Glucocorticoids and metabolism]. 0 79

Thyrotropin (10 muM) inhibited the antiviral activity of interferon. When added after interferon, thyrotropin (TSH) had no effect on antiviral activity. There was also no inhibition of interferon action in cells washed with medium between incubations with TSH and interferon. 125I-Labeled TSH and 125I-labeled cholera toxin could bind to preparations of mouse L-cell plasma membranes. The binding was specific in that it was prevented by unlabeled thyrotropin or cholera toxin, but not by insulin, glucagon, prolactin, growth hormone, human chorionic gonadotropin, or luteinizing hormone. Mouse interferon inhibited 125I-labeled TSH binding to L-cell plasma membranes. The effect of mouse interferon on 125I-labeled cholera toxon binding was more complex, inhibition occurring only after an initial enhancement at low interferon concentrations. A 10-fold higher concentration of interferon was required to inhibit 125I-labeled TSH binding. Mouse interferon was also able to displace bound 125I-labeled TSH, but not bound 125I-labeled cholera toxin. The interferon interaction with cell membranes was temperature-sensitive. Human interferon could induce changes in binding of 125I-labeled TSH and 125I-labeled cholera toxin to mouse L-cell plasma membranes similar to those induced by mouse interferon. Mouse interferon induced similar changes in plasma membranes of human KB-3 cells, which are insensitive to both human and mouse interferons. In view of these results, the species specificity of interferons does not appear to reside solely at the point of the initial interaction with their binding sites.
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PMID:Use of thyrotropin and cholera toxin to probe the mechanism by which interferon initiates its antiviral activity. 1 May 73

The neuroleptic drugs used in anesthetics belong to the group of phenothiazines or butyrophenones. The endocrine response to their intravenous administration is still ill-known and usually only concerns the association of anesthetics and neuroleptics. However, as far as the catecholamines are concerned, it is known that neuroleptic drugs do not prevent either their secretion nor their liberation but, depending on their dosage, they block the dopaminergic receptors and the alpha-receptors and induce disturbances in the metabolism of the mono-amines. The injection of neuroleptics associated with analgesics, raises the blood levels of catecholamines, does not induce a rise in ACTH and cortisol levels in the absence of stress, but does not totally prevent their rise in cases of aggression. As far as growth hormone is concerned, the effects are variable depending on the association studied. There is a rise with droperidol + pethidine or pentazocine, no change with chloroprotixene-dextromoramide. In both cases, the blood sugar rises. As far as STH, or growth hormone, free fatty acids and insulin are concerned, one may note a rise with associations containing droperidol even in the absence of any stress and stability with a mixture of chlorprotixene and dextromoramide. With none of these well known associations was there any variation either in levels of pituitary thyreo-stimulin, nor in thyroxine levels. Testosterone becomes reduced with the association of droperidol + analgesics but this effect does not seem to be specific to droperidol. These responses are frequently disturbed in case of additional stress.
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PMID:[Endocrine effects of neuroleptics]. 1 91

Patients with inflammatory bowel disease (IBD) manifest growth failure which may antecede abdominal symptoms by some years. Eight of ten children with documented IBD had records of decreasing growth velocities. Investigation of growth hormone reserves showed excessive rather than impaired responses. Mean basal GH level was 6.2 +/- 0.75 (SEM) ng/ml. During sleep, the mean GH level rose to 26.0 +/- 4.7 ng/ml and following propranolol-glucagon stimulation, to 46.0 +/- 4.5 ng/ml. All values were significantly higher than levels obtained in a control population of 25 children investigated for short stature who were not GH deficient. The mean peak GH response following insulin in the IBD group (10.8 +/- 3.8 ng/ml), however, did not differ from the mean peak response in the control group (13.5 +/- 3.3 ng/ml). Growth failure in patients with IBD is not the result of GH deficiency and is not an irreversible phenomenon. On the contrary, judicious use of glucocorticoids aimed at the control of the disease usually produces compensatory growth acceleration ("catch-up growth").
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PMID:Basal and stimulated serum growth hormone concentrations in inflammatory bowel disease. 1 69

The effects of varying levels of exercise on oxygen uptake, CO2 production, blood pressure, arterial blood gasses, and arterial concentrations of glucose, insulin, and growth hormone were examined in ten normal weight and ten moderately overweight young men. At comparable external work loads with a bicycle ergometer, the lean men required less oxygen than the obese men. When oxygen uptakes were matched during exercise on a treadmill, the lean men were walking on a steeper grade or at a higher rate than the obese men. The efficiency of exercise as assessed by the relation between oxygen uptake and work did not differ between the two groups. Blood pressure rose more in the obese during exercise than in the lean. The fall in lactate and rise in bicarbonate was of greater magnitude during cycle ergometry than during treadmill exercise. Obese and lean men, however, showed similar changes. With each level of exercise, there was a fall in arterial insulin levels, but the concentrations in the blood of overweight men always remained significantly above that of the normal men. Growth hormones tended to be higher in the normal weight men, but the differences were usually not significant, and there was no significant rise with exercise in either group until the highest levels of work were achieved. Glucose concentrations tended to be higher in the obese men, but fell to constant levels in both groups during exercise. Blood pressure rose to a greater extent in the overweight men during exercise.
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PMID:Some respiratory and metabolic effects of exercise in moderately obese men. 1 81


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