Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes.

Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes. Research Abstract Details 

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Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes. Abstract Text:

Rafael Medina-Navarro,Alberto M ,Margarita ,Genoveva Duran-Reyes,Clara Ortega-Camarillo,Ivonne M Olivares-Corichi, Hicks,Rafael Medina-Navarro,Alberto M ,Margarita ,Genoveva Duran-Reyes,Clara Ortega-Camarillo,Ivonne M Olivares-Corichi, Hicks,

Lipid peroxidation induced by reactive oxygen species might modify circulating biomolecules because of the formation of alpha,beta-unsaturated or dicarbonylic aldehydes. In order to investigate the interaction between a lipoperoxidation product, acrolein, and a circulating protein, insulin, the acrolein-insulin adduct was obtained. To characterize the adduct, gel filtration chromatography, sodium dodecylsulfate-polyacrylamide gel electrophoresis and carbonyl determination were performed. Induction of hypoglycemia in the rat and stimulation of glucose uptake by 3T3 adipocytes were used to evaluate the biological efficiency of the adduct compared with that of native insulin (Mackness, B., Quarck, R., Verte, W., Mackness, M., and Holvoet, P. (2006) Arterioscler., Thromb. Vasc. Biol. 26, 1545-1550). Formation of the acrolein-insulin complex in vitro increased the carbonyl group concentration from 2.5 to 22.5 nmol/mg of protein, and it formed without intermolecular aggregates (Halliwell, B., and Whiteman, M. (2004) Br. J. Pharmacol. 142, 231-255. The hypoglycaemic effect 18 min after administration to the rat is decreased by 25% (Robertson, R. P. (2004) J. Biol. Chem. 279, 42351-42354. An adduct concentration of 94 nM, compared to 10 nM for native insulin, was required to obtain the A 50% (concentration needed to obtain 50% of maximum transport of glucose uptake by 3T3 adipocytes). In conclusion, formation of the acrolein-insulin adduct modifies the structure of insulin and decreases its hypoglycemic effect in rat and glucose uptake by 3T3 adipocytes. These results help explain how a toxic aldehyde prone to be produced in vivo can structurally modify insulin and change its biological action.

Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes. Publishing Authors By Initials

R Medina-Navarro,AM ,M ,G Duran-Reyes,C Ortega-Camarillo,IM Olivares-Corichi,JJ Hicks,R Medina-Navarro,AM ,M ,G Duran-Reyes,C Ortega-Camarillo,IM Olivares-Corichi,JJ Hicks,

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Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Chemical research in toxicology

VOLUME: 20

Page Numbers: 1477-81

Journal Abbreviation: Chem. Res. Toxicol.

ISSN: 0893-228X

DAY: 6

MONTH: 09

YEAR: 2007

Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes. Information

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LANGUAGE: eng

NlmUniqueID: 8807448

Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes. Keywords Mesh Terms:

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Grant and Affiliation Information for Formation of an adduct between insulin and the toxic lipoperoxidation product acrolein decreases both the hypoglycemic effect of the hormone in rat and glucose uptake in 3T3 adipocytes.

AFFILIATION: Laboratorio de Metabolismo Experimental, Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, Morelia, Michoacán, Mexico.

Country: United States

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MEDLINETA: Chem Res Toxicol

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