Diacylglycerols Modulate Insulin Action in Rat Adipocytes

Terry, Maria Sylvester; Levy, James R.; Grunberger, George

doi:10.1055/s-2007-1003670

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…Therefore the only noncationic hexagonal phase promoter included in these studies was DiC8. Although we did not observe an effect of DiC8 on receptor phosphorylation in NIH 3T3 HIR 3.5 cells, studies in rat adipocytes showed a stimulation of insulin receptor tyrosine phosphorylation in response to this additive (Terry et al, 1991). Studies in cultured human monocytes and lymphoblastoid cells also showed increased tyrosine kinase activity both in intact cells and with the isolated insulin receptor (Grunberger & Levy, 1990).…”

Section: Discussioncontrasting

confidence: 84%

Insulin Receptor Autophosphorylation and Signaling is Altered by Modulation of Membrane Physical Properties

McCallum

Epand²

1995

Biochemistry

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Many membrane functions are modulated by the bulk biophysical properties of the membrane. Various compounds which alter membrane physical properties were investigated for their ability to modulate insulin receptor autophosphorylation and signaling. Compounds which raise the bilayer to hexagonal phase transition temperature in model membranes, including carbobenzoxydipeptides, apolipoprotein A-I, acyl carnitines, and lysophosphatidylcholine, inhibited insulin stimulation of insulin receptor tyrosine phosphorylation of isolated receptors as well as in cells overexpressing human insulin receptor. For compounds of similar structure, the inhibition of insulin receptor tyrosine phosphorylation correlates well with their bilayer-stabilizing potency. Most of the compounds which inhibit tyrosine phosphorylation of the insulin receptor also inhibited glucose uptake in the same cells. Compounds which lower the bilayer to hexagonal phase transition temperature in model membranes enhanced insulin stimulation of autophosphorylation in isolated receptors, with no effect on insulin receptor activity in NIH 3T3 HIR 3.5 cells. The effects of cationic amphiphiles were not readily predictable from their membrane modulating activity. All of the compounds tested exert their effects independent of changes in insulin binding to the receptor or changes in the basal tyrosine kinase activity of the receptor. This provides evidence that mechanism of modulation of insulin signaling by these additives lies in their ability to alter the bulk physical properties of the membrane. The results suggest that membrane monolayer curvature strain is a factor contributing to the efficiency of insulin signal transduction.

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Section: Discussioncontrasting

confidence: 84%

Insulin Receptor Autophosphorylation and Signaling is Altered by Modulation of Membrane Physical Properties

McCallum

Epand²

1995

Biochemistry

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Insulin resistance in a case of coexisting insulinoma and type 2 diabetes

Grunberger

1993

Acta Diabetol

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Hyperinsulinaemia due to pancreatic beta-cell tumours has been reported to lead to insulin resistance. A possible contribution of dysregulated insulin receptors to the impaired insulin action of insulinoma has not been explored. Therefore, we studied insulin receptor function in a patient with insulin-producing adenoma. This patient was rather unusual in that she was found to have a very large tumour and strikingly high circulating levels of insulin. In addition, her previous history included type 2 (non-insulin-dependent) diabetes mellitus. We confirmed decreased glucose utilization and metabolic clearance rate for glucose in presence of marked endogenous hyperinsulinaemia (approximately 2000 pM). 125I-labelled insulin binding capacity and receptor affinity for insulin were normal in her intact blood monocytes and erythrocytes. Insulin receptors were purified from the patient's tumour as well as from the pancreas, omental fat, liver and erythrocytes. All parameters of insulin binding to these receptors were normal. Thus, no evidence of receptor downregulation due to the marked hyperinsulinaemia was found. As expected, addition of insulin in vitro stimulated receptor autophosphorylation and tyrosine kinase activity of the receptors isolated from the liver, fat and erythrocytes. However, the basal tyrosine kinase activities of the tumour and pancreatic receptors were very high when isolated and further addition of insulin in vitro increased the protein kinase activity only slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

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Diacylglycerols Modulate Insulin Action in Rat Adipocytes

Cited by 2 publications

References 15 publications

Insulin Receptor Autophosphorylation and Signaling is Altered by Modulation of Membrane Physical Properties

Insulin Receptor Autophosphorylation and Signaling is Altered by Modulation of Membrane Physical Properties

Insulin resistance in a case of coexisting insulinoma and type 2 diabetes

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