Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors examined 48 patients with different endocrine pathology (relatives of patients with diabetes mellitus with a normal glucose tolerance test, patients with diabetes mellitus, obesity, thyrotoxicosis, and hypothyroidism) and a group of healthy persons. Blood glucagon concentration was determined radioimmunologically on fasting stomach and against the background of insulin hypoglycemia. A marked reduction of glucagon on fasting stomach was noted in patients with diabetes mellitus, and a reduction of the hormone concentration 30 and 60 min after the insulin injection. In obese patients and relatives of diabetic patients the initial blood glucagon level was not different from that in healthy persons. At the same time there was a significant reduction, and in relatives of diabetes patients also a retardation of glucagon secretion against the background of insulin hypoglycemia. The pattern of glucagon secretion in thyrotoxicosis and hypothyroidism proved to be changed.
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PMID:[Glucagon secretion in several endocrine diseases]. 36 65

In order to evaluate simultaneously in thyrotoxic subjects the relative contributions of insulin secretion, insulin-sensitivity (SI) and glucose-mediated (SG) glucose disposal to overall glucose tolerance, seven non-obese patients with thyrotoxicosis were studied by the minimal model analysis of the frequently sampled intravenous glucose tolerance test, before and greater than 1 month after being rendered euthyroid, and compared with eight healthy control subjects. Basal glucose, C-peptide and glucagon levels were similar in all groups but, in the toxic and euthyroid states, basal insulin levels were significantly elevated compared to the control group (11.2 +/- 2.0 and 7.9 +/- 1.1 vs 5.1 +/- 0.6 microU/ml, mean +/- SE, P less than 0.02). FFA levels were raised in the thyrotoxic subjects prior to treatment (0.95 +/- 0.11 vs 0.68 +/- 0.08 and 0.54 +/- 0.08 mmol/l, P less than 0.02). Glucose tolerance (Kg) was reduced in the thyrotoxic subjects compared to the euthyroid state (1.16 +/- 0.12 vs 1.44 +/- 0.13 per min, P less than 0.025) and control group (1.44 +/- 1.0 per min, 0.05 less than P less than 0.1). First phase (phi 1) and second phase (phi 2) insulin release were both significantly elevated in the thyrotoxic and euthyroid states compared to the control group (phi 1 7.10 +/- 1.88 and 5.29 +/- 1.03 vs 1.72 +/- 0.17 microU/mg/min X 10(-2), P less than 0.01; phi 2 18.64 +/- 3.14 and 16.74 +/- 4.48 vs 9.23 +/- 0.74 microU/mg/min X 10(-2) respectively, P less than 0.02). SG was similar in all groups but SI was significantly reduced in the thyrotoxic subjects compared to the control group (2.24 +/- 0.62 vs 5.92 +/- 1.50/min/microU/ml X 10(4), P less than 0.02) and rose post-treatment in the euthyroid subjects (4.23 +/- 1.75/min/microU/ml X 10(4)). In the thyrotoxic subjects before and after treatment, log SI correlated negatively with basal FFA levels (r = -0.57, P less than 0.05) and with phi 2 (r = -0.58, P less than 0.05). The fractional clearance rate of insulin was unaltered by the thyrotoxic state. It is concluded that in thyrotoxicosis the impairment of Kg is due to reduced insulin sensitivity in the presence of enhanced insulin secretion, but glucose-mediated glucose disposal is unaltered by the toxic state.
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PMID:Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in thyrotoxicosis: a minimal model analysis. 222 90

The effect of thyroid hormone excess on hepatic glucose balances and fractional hepatic extraction of insulin and glucagon was examined in six conscious dogs with catheters in the portal vein, hepatic vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. An oral glucose tolerance test was performed before and after the animals were made hyperthyroid by intramuscular thyroxine administration (100 micrograms.kg-1.day-1) for 10 days. In the basal state and after oral glucose, insulin and glucagon levels in the three vessels and the basal fractional hepatic extraction of insulin and glucagon were not significantly modified by thyroid hormone. These results suggest that in short-term thyrotoxicosis insulin secretion is not impaired, and the rise in fasting plasma glucose and increased hepatic glucose production could reflect hepatic insulin resistance, increased availability of precursors for gluconeogenesis, or increased glycogenolysis. Hyperthyroidism significantly increased basal flows in the portal vein (14.7 +/- 0.6 vs. 12.9 +/- 0.5 ml.kg-1.min-1), the hepatic artery (4.8 +/- 0.3 vs. 3.9 +/- 0.2 ml.kg-1.min-1) and vein (19.6 +/- 0.7 vs. 16.9 +/- 0.4 ml.kg-1.min-1), the fasting plasma glucose concentration (104 +/- 3 vs. 92 +/- 2 mg/dl), and basal hepatic glucose output (2.1 +/- 0.2 vs. 1.5 +/- 0.2 mg.kg-1.min-1). It did not alter the nonhepatic splanchnic uptake of glucose, the percent of orally administered glucose that appeared in the portal vein (47 +/- 2 vs. 45 +/- 11%), the percent of hepatic uptake of glucose (59 +/- 11 vs. 74 +/- 22%), or the shape of the glucose tolerance test.
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PMID:Fasting and postabsorptive hepatic glucose and insulin metabolism in hyperthyroidism. 264 38

To clarify the contribution of gastrointestinal function to impaired oral glucose tolerance in hyperthyroidism, gastric emptying rate and portal and peripheral blood glucose responses to intragastric or intraduodenal glucose administration were investigated in experimental thyrotoxic rats. Glucose absorption from perfused intestine of thyrotoxic rats was also examined. Thyrotoxicosis was induced by subcutaneous (SC) thyroxine injection (50 micrograms/kg/d) for seven days. In intragastric glucose tolerance test, although insulin and glucagon responses were not significantly altered, increments in portal and peripheral blood glucose were significantly higher in thyrotoxic rats than in controls at 30 minutes. This phenomenon was almost normalized by the preadministration of phentolamine (2 mg/kg SC). In intraduodenal glucose tolerance test, blood glucose, insulin, and glucagon responses were similar in thyrotoxic and control rats. Gastric emptying rate in thyrotoxic rats was significantly higher than that in controls at 30 minutes, and that was also normalized by phentolamine administration. Absorption of glucose from perfused intestine was similar in thyrotoxic and control rats. These results suggest that an altered glucose tolerance to intragastric glucose load in thyrotoxic rats may primarily be due to rapid gastric emptying induced by increased alpha-adrenoceptor responses, and that glucose absorption from small intestine was not increased in short-term thyrotoxic rats.
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PMID:Glucose tolerance and gastric emptying in thyrotoxic rats. 267 99

The responses in plasma glucose, insulin, C-peptide, glucagon and somatostatin to an oral glucose load were studied in 10 thyrotoxic patients and 10 matched euthyroid controls. The thyrotoxic patients had higher mean fasting plasma glucose (P less than 0.05) and responded to oral glucose with an earlier peak at 30 min which was higher than the corresponding glucose level in the controls (P less than 0.05). Impaired glucose tolerance was found in 3 patients. Fasting insulin and C-peptide levels were normal in the thyrotoxic patients when corrected for the higher glucose levels. Following glucose ingestion, there was no significant difference between the areas under the insulin or C-peptide curves in patients and controls, but Seltzer's insulinogenic index was reduced in the patients (P less than 0.01) suggesting an impaired pancreatic B-cell response to oral glucose. Mean basal glucagon was normal in the thyrotoxic patients. However, while in the controls plasma glucagon became suppressed following glucose ingestion (P less than 0.0001), no significant suppression was found in the patients. In the thyrotoxic patients, mean basal somatostatin was normal, but the area under the somatostatin curve following glucose ingestion was significantly increased (P less than 0.02). Our findings suggest that decreased glucagon suppression and impaired insulin response after glucose ingestion are involved in glucose intolerance in thyrotoxicosis. Enhanced somatostatin responses to oral glucose in thyrotoxicosis may have contributed to the observed impairment in pancreatic B-cell responsiveness.
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PMID:Glucose intolerance in thyrotoxicosis roles of insulin, glucagon and somatostatin. 288 18

Long-acting somatostatin analogues such as SMS 201-995 (Sandoz) are being evaluated in a wide range of clinical indications, including gut neuroendocrine tumours and acrogemaly. Long-term continuous SMS 201-995 treatment has achieved useful symptomatic improvement in diarrhoea in 4 patients with metastatic VIPomas who had relapsed following previous treatment. Clinical improvement has outlasted suppression of VIP secretion (suggesting an additional direct antisecretory action of SMS 201-995) and has occurred despite expansion of hepatic metastases. In 6 patients with tumours secreting gastrin and/or glucagon, secretion of these peptides was acutely inhibited by SMS 201-995. However, endocrine and clinical responses to chronic treatment have been less consistent. SMS 201-995 is active orally at doses of 4-8 mg and when given thrice-daily to 6 patients with active acromegaly, suppressed mean 24-h growth hormone levels by 51-88%. Despite significantly reduced plasma insulin concentrations, glucose tolerance did not deteriorate. SMS 201-995 was also effective in suppressing thyroid-stimulating hormone (TSH) and thyroid hormone secretion in a patient with mild thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion. In all cases SMS 201-995 treatment has been well tolerated and has few side-effects.
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PMID:Clinical evaluation of SMS 201-995. Long-term treatment in gut neuroendocrine tumours, efficacy of oral administration, and possible use in non-tumoural inappropriate TSH hypersecretion. 289 35

This report describes a new method for detecting and quantitating those immunoglobulins G (IgG) in serum that are related to Graves' disease. The method is based on previous observations which indicate that the guinea pig fat cell membrane (FCM) is capable of binding Graves'-specific IgG, but does not bind the IgG common to Graves' disease and Hashimoto's disease, such as antimicrosomal antibodies. Crude FCM preparations were iodinated by a lactoperoxidase technique and were then treated with Triton X-100 to yield a solubilized radioiodinated FCM (SFCM) preparation. SFCM, which retained bovine (b) TSH binding and Graves'-IgG binding properties, provided a radioactively labeled receptor with which to test for the presence of fat cell-binding IgG (FBI) in immunoprecipitates prepared by reacting these IgG with antibody against the Fc fragment of human IgG. FBI values (percentage of added SFCM bound to immunoprecipitate; mean + SD) in IgG from 16 patients with thyrotoxicosis caused by Graves' disease (6.0 +/- 1.7) were completely separated from those in IgG from 16 normal subjects (0.4 +/- 0.3). IgG from 2 hypothyroid patients with Hashimoto's disease, which were strongly positive in the TSH binding inhibition (TBI) assay, yielded FBI values within the range in Graves' disease, but values in TBI-negative IgG from 15 other patients with Hashimoto's disease were normal (0.0 +/- 0.9). Moderately false positive FBI values were found in the IgG of 15 patients with rheumatoid arthritis or systemic lupus erythematosis, all rheumatoid factor positive, 3 of which were also TBI positive. In IgG from Graves' disease and those from patients with TBI-positive collagen-vascular disease, binding of SFCM was inhibited by bTSH in a dose-dependent manner. As with binding of TSH to thyroid plasma membranes, similar but less potent inhibition of binding of IgG to SFCM was produced by LH, FSH, and hCG, but not by insulin, glucagon, PRL, or ACTH. FBI values in TBI-negative IgG from patients with collagen-vascular disease were also decreased by TSH, but higher concentrations of bTSH were required. In 40 IgG from among the various clinical groups tested, a significant correlation was found between FBI values and TBI activity (r = 0.48; P less than 0.01). In addition, among 10 IgG from Graves' disease and 6 from collagen-vascular disease patients, a very close correlation (r = 0.89; P less than 0.001) was noted between their TBI activity and the extent to which their FBI values were decreased by a standard concentration of bTSH.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Detection and measurement of fat cell-binding immunoglobulins: a new method applicable to the diagnosis and study of Graves' disease. 299 73

To elucidate the possible role of insulin, glucagon, and epinephrine on glucose intolerance in thyrotoxicosis, the secretion of insulin and glucagon in vivo (glucose, arginine, and epinephrine infusion tests) and in perfused pancreas and the hepatic action of insulin, glucagon, and epinephrine in perfused liver were investigated in experimental thyrotoxic rats (induced by thyroxine injection, 20 micrograms/kg sc, for 7 days). In thyrotoxic rats, fasting blood glucose (87 +/- 5 mg/dl, mean +/- SD) and plasma insulin (16 +/- 3 microU/ml) were significantly (P less than 0.001) higher than those in controls (74 +/- 5 mg/dl and 8 +/- 1 microU/ml), respectively. In glucose infusion test (0.5 g/kg iv), blood glucose, plasma insulin, and glucagon responses in thyrotoxic rats were not significantly different from those in controls. In arginine infusion test (5 mg/min for 20 min iv), the increments in blood glucose and plasma insulin after arginine in thyrotoxic rats were not significantly different from those in controls. Plasma glucagon response was almost the same in both groups. In epinephrine infusion test (100 micrograms/kg iv), the increments in blood glucose and plasma insulin in thyrotoxic rats were significantly greater than those in controls. In perfused pancreas, insulin and glucagon secretions in response to 16.7 mM glucose or 6.4 mM arginine in the presence of 5.5 mM glucose in thyrotoxic rats were not different from those in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose intolerance in thyrotoxic rats: role of insulin, glucagon, and epinephrine. 305 20

Pancreatic alpha and beta cell hormone secretion was studied in 11 patients with thyrotoxicosis before and in 7 patients after thyroid function was normalized with either prophylthiouracil or methimazole and propranolol (R). All had IV arginine and IV glucose infusions. Forty control subjects had IV arginine; 21 had IV glucose tests. After arginine, untreated patient had blunted serum insulin at both 15 and 30 minutes (p less than 0.05, p less than 0.001) compared to control subjects, blunted glucagon at 30 minutes (p less than 0.05) and blunted glucose at both 15 and 30 minutes (p less than 0.001, p less than 0.01) compared to control subjects. After glucose, untreated patients had lower nadir glucagon than in the studies with both arginine and glucose infusions. These data document blunted glucagon, suppressed glucose and insulin peaks after arginine in thyrotoxicosis, indicate that both alpha and beta cell hormone secretion may be abnormal, and that the preferential abnormality follows protein rather than carbohydrate loading.
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PMID:Defective pancreatic alpha and beta cell secretion in thyrotoxicosis. 390 51

The plasma adenosine 3', 5' - cyclic monophosphate (cyclic AMP) response to 50 micrograms of intravenous glucagon was examined in 14 normal euthyroid subjects, 15 patients with thyrotoxicosis and 5 patients with myxedema. The cyclic AMP responses to 50 micrograms of intravenous glucagon was significantly higher in the hyperthyroid group than in the euthyroid or hypothyroid group. However, the areas of overlap between all three groups were large and there was little relationship between the plasma cyclic AMP response to glucagon and the biochemical assessment of thyroid function. Serial studies of the response to 50 micrograms glucagon were carried out in four patients receiving treatment for thyrotoxicosis. Again, there was not consistent relationship between the plasma cyclic AMP responsiveness to glucagon and the free thyroxine index. It is concluded that although the plasma cyclic AMP response to glucagon is increased in thyrotoxicosis and decreased in myxedema, the variability of this response in thyroid disease precludes its use as a tissue index of thyroid hormone responsiveness.
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PMID:Investigation of the usefulness of the plasma adenosine 3' 5' - cyclic monophosphate response to glucagon in thyroid disease. 625 51


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