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)

Coexistence of hyperinsulinemia and normal or impaired carbohydrate tolerance indicates insulin resistance which is frequently observed in patients with liver diseases such as liver cirrhosis, fatty liver, acute and chronic hepatitis and idiopathic haemochromatosis. Insulin resistance in liver diseases can be due to circulating insulin antagonists or a target tissue defect in insulin action, either due to changes in the state of the insulin receptor or due to a postreceptor defect, that means any abnormality in the insulin action sequence following the initial binding step. High insulin levels in liver diseases are caused by diminished degradation of insulin by the liver whereas hypersecretion only plays a minor role under basal conditions. High levels of glucagon, free fatty acids and growth hormone are well known in liver diseases but until now there is no evidence of the pathogenetic importance of these factors. Conflicting results on insulin binding, methodological criticism on binding data and the question whether or not diminished insulin binding on peripheral blood cells plays any physiological role make it unlikely that studies on insulin receptors of peripheral blood cells contribute to the revelation of insulin resistance in liver diseases. The clamp technique allows to quantify the sensitivity of the body to exogenous insulin. The results on liver cirrhosis in connection with studies on glucose metabolism show that under basal conditions insulin insensitivity is due to peripheral resistance (primarily muscle) according to a postreceptor defect. Finally the causes of insulin resistance in liver diseases are still not known.
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PMID:[Insulin resistance in liver diseases]. 353 94

To elucidate the mechanism of glucagon-insulin (G-I) therapy, the effect of insulin and/or glucagon on the insulin receptor was studied in an experiment utilizing cultured cells (JTC-16) of rat ascites hepatoma. Insulin specific receptors were present on JTC-16 cells and were similar in nature to the receptors of primary culture rat hepatocytes. There were two kinds of insulin receptors. One had a high insulin affinity and the other had low insulin affinity. In the experiment involving addition of insulin the number of insulin receptors decreased after 24 hrs incubation in proportion to the increase in added insulin concentration. On the other hand, the number of insulin receptors increased with glucagon addition and the increase in proportion to the concentration of glucagon added. In the experiment involving simultaneous addition of insulin and glucagon, a 20% decrease in the number of receptors induced with 10(-9) M insulin was restored to the control level with simultaneous glucagon addition of the same concentration. The number of insulin receptors increased as the concentration of additive glucagon increased. These results show that simultaneous addition of insulin and glucagon inhibits the decrease in number of insulin receptors with insulin alone. These facts may obtain more potent action of insulin in G-I therapy via insulin receptor.
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PMID:The effect of insulin and glucagon on the insulin receptor of cultured hepatoma cells. 353 98

The effect of a new diuretic, piretanide, on glucose tolerance, insulin secretion and 125I-insulin binding to erythrocytes was studied in 12 male patients with mild essential hypertension. After a 4 week wash-out period with placebo, piretanide 6 mg b.i.d. was administered in a single-blind manner for 8 consecutive weeks. Although glucose tolerance deteriorated slightly in one patient, the diuretic treatment had no effect on the mean blood glucose concentrations during oral glucose tolerance tests or on glycohaemoglobin A1 measurements, both studies being done at 4 week intervals. Preservation of euglycemia was associated with increased insulin secretion. After 8 weeks of piretanide therapy the basal C-peptide concentration was 61% higher than the pretreatment level (0.44 vs 0.71 microU/ml; p less than 0.05). Glucagon - stimulated C-peptide concentrations were significantly elevated after 4 (1.67 vs 2.53 microU/ml, p less than 0.05) and after 8 weeks (1.67 vs. 2.90 microU/ml, p less than 0.01) of diuretic treatment. Fasting plasma immunoreactive insulin (IRI) levels were virtually unchanged by the drug therapy. The enhanced insulin secretion did not appear secondary to increased insulin resistance at the insulin receptor level, since the specific bound fraction of 125I-insulin remained unaffected by diuretic treatment. Although short-term loop diuretic treatment appears to have no effect on glucose tolerance, the very low density lipoprotein synthetic rate may be promoted by the increased insulin secretion.
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PMID:Effects of a new diuretic piretanide on glucose tolerance, insulin secretion and 125I-insulin binding. 388 96

A method is described for preparing a plasma-membrane fraction from hepatocytes by a rapid, gentle, Percoll fractionation procedure. Cholera toxin elicited the ribosylation of a number of proteins in these membranes, including the components of the stimulatory guanine nucleotide regulatory protein, Ns. Insulin, however, inhibited the ability of cholera toxin to ribosylate a protein of Mr 25 000. The action was decreased in membranes from cells that had been pre-treated with glucagon. Ribosylation of both the components of Ns and the Mr-25 000 species occurred in whole cells treated with cholera toxin, because membranes from such treated cells exhibited decreased labelling when incubated with [32P]NAD+ and activated cholera toxin. The labelling of proteins, including the Mr-25 000 species, with [32P]NAD+ and cholera toxin in the plasma membranes was decreased by an inhibitor of ribosylation. Azido-GTP photoaffinity labelling identified several high-affinity GTP-binding proteins, including one of Mr 25 000. Cholera toxin failed to ribosylate the Mr-25 000 protein in membranes from cells that had been pre-treated with the tumour-promoting agent 12-O-tetradecanoylphorbol 13-acetate (TPA). In membranes from such treated cells, insulin actually allowed cholera toxin to label this species. As TPA activates protein kinase C, it is possible that the Mr-25 000 protein, or a species that interacts with it, is a substrate for phosphorylation. These observations may offer an explanation for some of the perturbing effects that TPA exerts on insulin's action. It is suggested that the insulin receptor interacts with the guanine nucleotide regulatory protein system in the liver, and that the Mr-25 000 species may be a component of Nin, a specific guanine nucleotide regulatory protein that has been proposed to mediate certain of the actions of insulin on target cells [Houslay & Heyworth (1983) Trends Biochem. Sci. 8, 449-452].
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PMID:Insulin inhibits the cholera-toxin-catalysed ribosylation of a Mr-25000 protein in rat liver plasma membranes. 389 32

This report describes a 3-month-old female infant with the typical physical features of leprechaunism. The patient demonstrated glucose intolerance and marked hyperinsulinemia (4600 microU/ml). Since an intravenous insulin injection (actrapid insulin: 0.15 U/kg) caused no significant decrease in the blood glucose level, the presence of insulin resistance was suggested. Neither insulin antibodies nor insulin receptor antibodies were were found in the patient's plasma, and other circulating insulin antagonists such as glucagon, growth hormone, and cortisol were within normal limits. [125I]Insulin binding to the erythrocytes from the patient was as low as 1.02% (control infants: 4.89 +/- 1.08% [mean +/- SD]). [125I]Insulin binding to the cultured transformed lymphocytes from the patient was similarly reduced to 3.58% (control: 20.9 +/- 2.71% [mean +/- SD]). From these findings we concluded that the insulin resistance was due to a primary defect in insulin receptors. Interestingly, transient remissions of the patient's glucose intolerance and hyperinsulinemia were observed during a year of follow-up study. The insulin tolerance test which was performed at the remission period showed an improvement in insulin resistance. However, the insulin binding defect to erythrocytes remained unchanged even at the remission period. The exact cause of these remissions was not clear and remained to be elucidated.
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PMID:[A case of leprechaunism with extreme insulin resistance due to a primary defect in insulin receptors]. 391 Apr 62

Serum insulin and glucagon levels and liver plasma membrane receptor binding were studied in rats after partial hepatectomy. To clarify whether the surgical stress and decreased food intake that accompanies partial hepatectomy influenced these parameters, sham-operated rats were also studied. When sham-operated rats were compared to nonoperated controls, there was a 30% fall in insulin levels and a significant rise in the number of insulin receptors. In contrast, glucagon levels and glucagon receptor binding were unchanged. When partially hepatectomized rats were compared to sham-operated rats, there was no significant change in either insulin levels or the number of plasma membrane insulin receptors. Insulin degradative activity, however, was decreased in liver plasma membranes from partially hepatectomized animals, causing an apparent increase in [125I]iodoinsulin binding to this organelle. Bacitracin, an inhibitor of insulin degradation, abolished this difference in insulin binding. Glucagon levels rose by 65% after partial hepatectomy, whereas the number of glucagon receptors decreased significantly. The studies demonstrate, therefore, that after partial hepatectomy, serum insulin levels and insulin receptor binding in liver are altered, and these alterations are due to surgical stress and decreased food intake. Glucagon levels and glucagon receptor binding are also altered after partial hepatectomy, but these alterations are due to liver regeneration per se.
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PMID:Regenerating rat liver: insulin and glucagon serum levels and receptor binding. 626 53

Insulin and glucagon secretion after glucose load and the hormone-receptor inter-action were compared between 6- and 24-month-old Wistar rats. The 24-month-old rats showed a failure to decrease glucagon secretion after glucose load in contrast to 6-month-old rats with a similar degree of glucose tolerance and insulin response. Age-related change of insulin receptor of rat livers was tentatively suggested to be a disappearance of the binding site with higher affinity. Affinity of the glucagon receptor did not differ significantly between the two groups. The hyposuppressibility of glucagon by hyperglycemia and the decrease of insulin affinity might contribute to the glucose intolerance with aging.
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PMID:Insulin insensitivity and hyposuppressibility of glucagon by hyperglycemia in aged Wistar rats. 627 41

Activation of T- and B-lymphocytes by a variety of immunological stimuli has been reported to induce specific insulin receptors. The purpose of the present work was to determine whether glucagon receptors are also induced in activated cells. Studies of glucagon and insulin receptors were carried out using normal human mononuclear cells activated by phytohemagglutinin or T-cell growth factor (TCGF), as well as established B- and T-lymphoblastoid cell lines. With phytohemagglutinin, glucagon and insulin binding increased 15- and 36-fold, respectively, and peaked after 5 days in parallel with the rise in thymidine incorporation. Increased binding was associated with an increase in the number of receptors, most marked for insulin, though affinity for the insulin receptor was decreased. Normal human mononuclear cells cultured with TCGF showed an early modest rise in insulin binding due to increased receptor number, without a change in affinity, and a striking and progressive rise up to 50-fold in glucagon binding due to both increased receptor number and affinity. The differences in receptor response to these T-cell mitogens suggest that TCGF selects out a T-lymphoblast subset with very high glucagon receptors. B- and T-lymphoblastoid cells showed patterns of glucagon and insulin receptors that appear to be characteristic for each cell type. Glucagon binding was 7-fold higher (P less than 0.01), while inulin binding was 7-fold lower (P less than 0.01) in T- vs. B-lymphoblastoid cells. T-Cell lines had twice the number of glucagon receptors, whereas B-lines had 4-fold the number of insulin receptors, with much greater affinity for insulin compared with T-line insulin receptors. Induction of both insulin and glucagon receptors on activated lymphoblasts suggests that these receptors may play a significant role in cell function.
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PMID:Expression of glucagon receptors on T- and B- lymphoblasts: comparison with insulin receptors. 628 89

Eighteen patients with postnecrotic cirrhosis of liver, including three patients who had had a portosystemic shunt operation, and 19 normal controls were studied. The tests performed included monocyte insulin receptor assay, iv glucose tolerance test, glucagon test, and insulin tolerance test. Insulin resistance was documented by the presence of fasting hyperglycemia and glucose intolerance together with hyperinsulinemia as well as resistance to exogenous insulin. The binding of [125I]insulin to monocyte insulin receptors was significantly decreased in cirrhotic patients compared with that in controls (P less than 0.02), and this was due to a significant decrease in the high affinity association constant (P less than 0.005). There was a significant negative correlation between the fasting insulin level and maximum [125I]insulin binding in cirrhotic patients (r = -0.8; P less than 0.02). Cirrhotics that had had a shunt operation showed a higher fasting insulin level, a greater insulin resistance, and a smaller maximum [125I]insulin binding to insulin receptors than those without shunt. All of these findings suggested a down-regulatory effect of hyperinsulinemia on the monocyte insulin receptors. An impaired glycemic response to glucagon was also found in cirrhotics, the exact mechanism of which remains to be elucidated. However, as the increases in plasma cAMP after glucagon were similar in cirrhotics and controls, the fault apparently did not lie in the glucagon receptor.
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PMID:Down-regulation of insulin receptors in postnecrotic cirrhosis of liver. 628 82

To gain insight into the mechanisms responsible for the impaired glycogenolytic response to glucagon and the diminished ketogenic capacity of newborn guinea pig, we studied the ontogeny of insulin and glucagon receptors, and the responsiveness of the adenylate cyclase complex to glucagon, PGE1, NaF, and cholera toxin in liver plasma membrane from fetal (58 d, late gestation, and 65 d, term) and adult guinea pigs. The number of insulin receptors (x 10(-10) M/L) was least in 58-d fetus (3.0 +/- 0.4; mean +/- SEM) and increased 3-fold in 65 d fetus (8.8 +/- 0.6; P less than 0.01). In adult guinea pig, both insulin receptor number (6.0 +/- 0.7) and average affinity constant (1.20 +/- 0.08 x 10(8) M-1) were significantly lower (P less than 0.01) compared with 65-d fetus. The number of glucagon receptors remained unchanged between 58-d and 65-d fetuses, but both average and high affinity association constants were significantly higher at d 65. In contrast to the lower capacity and affinity of insulin receptors in the adult compared with term fetus, the total glucagon receptor number (x 10(-10) M/L) in adults (7.2 +/- 0.8) was twice that of the 58 d (3.2 +/- 0.2) and 65 d (3.2 +/- 1.0) fetuses. The average affinity constant (x 10(8) M-1) in adult (3.8 +/- 0.2) was, however, significantly lower than the two fetal groups (58 d, 5.0 +/- 0.3; P less than 0.05 and 65 d, 8.1 +/- 1.0; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ontogeny of insulin and glucagon receptors and the adenylate cyclase system in guinea pig liver. 633 Jun 58


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