Cyclic AMP modulates insulin binding and induces post-receptor insulin resistance of glucose transport in isolated rat adipocytes

Kirsch, D.; Kemmler, Wolfgang; Häring, Hans‐Ulrich

doi:10.1016/0006-291x(83)91017-3

Cited by 37 publications

(15 citation statements)

References 15 publications

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“…These alterations are closely related to a glucagon-induced decrease in the affinity for insulin of the receptor [2].A decrease in afffinity was also observed in the cells which were preincubated with N6, 2-O-dibutyryl adenosine 3', 5'-cyclic monophosphate [2]. Results similar to our findings were also reported by others [3,4]. These observations suggested that the glucagon regulation of insulin action is mediated by cAMP-induced modification of insulin binding at the receptor level [5][6][7][8].…”

supporting

confidence: 82%

Adenosine 3',5'-Cyclic Monophosphate-Dependent Protein Kinase (A Kinase) Regulation of Insulin Receptor Function: Phosphorylation of Insulin Receptor with A Kinase Decreases the Insulin Binding Activity.

et al. 1991

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Abstract. The effect of phosphorylation of insulin receptor with adenosine 3', 5'-cyclic monophosphate-dependent protein kinase (A kinase) on its insulin binding activity was investigated by using insulin receptors prepared from rat liver in vitro. A 95 KDa protein was phosphorylated by stimulation of insulin receptor kinase. This protein was also phosphorylated by A kinase. Analysis of phosphoamino acid showed that tyrosine residue(s) was phosphorylated by activation of insulin receptor kinase, whereas phosphoserine and phosphothreonine were dominantly generated by activation of A kinase.[125I] Iodoinsulin binding activity was decreased by prior phosphorylation of the receptor with A kinase. Scatchard analysis showed that the affinity for insulin was decreased by the phosphorylation with A kinase. Although the maximal activity of insulin receptor kinase was not affected by phosphorylation with A kinase, the insulin concentration which induced half maximal activity (ED50) of the receptor kinase was increased by the phosphorylation with A kinase.These results suggested that counter regulatory hormones whose actions are mediated by the generation of adenosine 3', 5'-cyclic monophosphate regulate the insulin binding to the a subunit through phosphorylation of the ƒÀ subunit of insulin receptor.

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supporting

confidence: 82%

Adenosine 3',5'-Cyclic Monophosphate-Dependent Protein Kinase (A Kinase) Regulation of Insulin Receptor Function: Phosphorylation of Insulin Receptor with A Kinase Decreases the Insulin Binding Activity.

et al. 1991

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“…We have shown here that after a 72-h fast there is a decrease in JAK2 protein expression and a more marked decrease in insulin-induced JAK2 tyrosine phosphorylation. These results suggest a tissue-speci c regulation of amount of JAK2 tyrosine phosphorylation, given that in the liver of 72-h-fasted rats the insulin-induced tyrosine phosphorylation of this kinase is increased (31). Before insulin infusion, JAK2 tyrosine phosphorylation is also higher in fed rats, probably as consequence of the higher insulin levels these animals present.…”

Section: Discussionmentioning

confidence: 71%

“…An excess of epinephrine has long been known to cause insulin resistance (21,(31)(32)(33). Catecholamines antagonize the action of insulin by stimulating gluconeogenesis, glycogenolysis, and lipolysis and by inhibiting peripheral use of glucose by way of a b -adrenergic mechanism that may also involve a decrease in cellular glucose transport (21).…”

Section: Discussionmentioning

confidence: 99%

Regulation of Cardiac Jak‐2 in Animal Models of Insulin Resistance

Rojas¹,

Carvalho²,

Paez-Espinosa

et al. 2000

IUBMB Life

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Insulin induces phosphorylation and activation of JAK2 tyrosine, as well as its association with STAT1 and SHP2 in insulin-sensitive tissues of intact rats, thus demonstrating a new pathway in transduction of insulin signals. We investigated this pathway in hearts of rats in three situations of insulin resistance: 72 h of fasting, chronic treatment with dexamethasone, and acute treatment with epinephrine. The acute treatment with epinephrine showed no difference in insulin-induced JAK2 tyrosine phosphorylation or JAK2/STAT1 and JAK2/SHP2 association in comparison with the control. In fasted rats the JAK2 protein concentration decreased, accompanied by a decrease in the stoichiometry of the phosphorylation to 70%, an increase in association of JAK2/STAT1 to 160%, and a decrease in JAK2/SHP2 association to 85%. In the dexamethasone-treated group, the JAK2 protein concentrations increased but the stoichiometry of its phosphorylation decreased to 20%, whereas the JAK2/STAT1 and JAK2/SHP2 associations changed by 70% and 170%, respectively. In fasting and dexamethasone-treated rats, therefore, insulin-induced JAK2 tyrosine phosphorylation decreases, and the JAK2 protein expression is differentially regulated such that the insulin-induced JAK2 association with SHP2 and STAT1 shows opposite interactions with the kinase.

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“…Regarding the reports that cAMP potentiates the down-regulation of different hormone receptors i.e. : insulin receptors (Kirsch et al, 1983); it seems probable that the increased cAMP accumulation detected by us in adipocytes from streptozotocindiabetic rats could potentiate the downregulation of glucagon receptors in these cells. On the other hand, fat cells from diabetic rats were found to inactivate glucagon to the same extent, showing that the changes in glucagon binding were not due to differences in glucagon degradation at the time of binding.…”

Section: Discussionmentioning

confidence: 74%

Glucagon Binding and Lipolytic Response in Isolated Adipocytes from Streptozotocin-diabetic Rats.

Mayor

Calle

1988

Endocrinol Japon

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Evidence for pre-receptor, receptor and post-receptor glucagon defects was investigated in adipocytes from streptozotocin-diabetic rats. For this purpose male Wistar rats were injected by cardiac puncture with streptozotocin (65 mg/Kg body-weight) or saline solution and sacrificed after 7 and 15 days of drug administration.Increased glucagon levels and increased glucagon degradation in serum together with a decrease in glucagon binding were found in both groups of diabetic rats. The decrease in glucagon binding was related to a decrease in the number of glucagon receptors/cell rather than to a change in receptor affinity. The lipolytic response of glucagon was increased. However, the ability of glucagon to increase basal or theophylline-stimulated cAMP accumulation in the incubation medium of adipocytes from diabetic rats was decreased. Such alterations could represent a counter-regulatory mechanism of the hyperglucagonemia detected in streptozotocin-diabetic rats.

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Cyclic AMP modulates insulin binding and induces post-receptor insulin resistance of glucose transport in isolated rat adipocytes

Cited by 37 publications

References 15 publications

Adenosine 3',5'-Cyclic Monophosphate-Dependent Protein Kinase (A Kinase) Regulation of Insulin Receptor Function: Phosphorylation of Insulin Receptor with A Kinase Decreases the Insulin Binding Activity.

Adenosine 3',5'-Cyclic Monophosphate-Dependent Protein Kinase (A Kinase) Regulation of Insulin Receptor Function: Phosphorylation of Insulin Receptor with A Kinase Decreases the Insulin Binding Activity.

Regulation of Cardiac Jak‐2 in Animal Models of Insulin Resistance

Glucagon Binding and Lipolytic Response in Isolated Adipocytes from Streptozotocin-diabetic Rats.

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