The Lipid Peroxidation End-Product 4-Hydroxynonenal Induces Insulin Resistance in Isolated Rat Slow-Twitch Skeletal Muscle

Persistent Link:
http://hdl.handle.net/10150/297614
Title:
The Lipid Peroxidation End-Product 4-Hydroxynonenal Induces Insulin Resistance in Isolated Rat Slow-Twitch Skeletal Muscle
Author:
Giovannini, Franchesca J.; Prasannarong, Mujalin; Santos, Fernando R.; Henriksen, Erik J.
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
A primary defect leading to the development of type 2 diabetes is insulin resistance of the glucose transport system in skeletal muscle. One factor known to induce insulin resistance is oxidative stress. A by>product of lipid peroxidation is the reactive aldehyde 4-hydroxynonenal (4-HNE), an oxidant that induces a number of deleterious consequences on cell function. However, the impact of 4-HNE on the glucose transport system in rat slow>twitch skeletal muscle is currently not known. Therefore, we assessed the impact of 4-HNE on insulin signaling factors (IRS-1 protein expression and phosphorylation of Akt Ser473 (pAkt) and AS160 Thr642 (pAS160)) and on glucose transport activity in mammalian slow-twitch muscle. Strips of soleus muscle from lean Zucker rats were incubated with 4-HNE (50 μM) in the absence or presence of insulin (5 mU/ml) for up to 6 hr. Insulin>stimulated glucose transport activity (determined using 2-deoxyglucose uptake) was decreased by 4-HNE at 2 hr (30%), 4 hr (26%), and 6 hr (39%) (all p<0.05). At 2 hr of 4-HNE treatment in the presence of insulin, pAS160 was decreased by 28%, whereas pAkt was only reduced 11% and IRS-1 protein levels were not changed. At 4 hr, pAS160 was decreased by 22%, as was pAkt, and IRS-1 levels were 39% lower than in the control muscles. At 6 hr, pAS160 was 47% lower, pAkt was decreased by 26%, and IRS-1 protein levels were reduced by 51%. Interestingly, IRS-2 protein levels were decreased by 17% only at the 6 hr time point. In summary, these data indicate that the lipid peroxidation end>product and oxidant 4-HNE induces insulin resistance of glucose transport activity in rat slow>twitch skeletal muscle, initially associated with impaired phosphorylation (and therefore reduced activation) of AS160. Longer durations of 4-HNE exposure led to a greater impairment of Akt phosphorylation and to a selective loss of IRS-1 protein. These results provide further support for an important role of oxidative stress in the etiology of skeletal muscle insulin resistance.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
bachelors
Degree Program:
Honors College; Physiology
Degree Grantor:
University of Arizona
Advisor:
Henriksen, Erik

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleThe Lipid Peroxidation End-Product 4-Hydroxynonenal Induces Insulin Resistance in Isolated Rat Slow-Twitch Skeletal Muscleen_US
dc.creatorGiovannini, Franchesca J.en_US
dc.contributor.authorGiovannini, Franchesca J.en_US
dc.contributor.authorPrasannarong, Mujalinen_US
dc.contributor.authorSantos, Fernando R.en_US
dc.contributor.authorHenriksen, Erik J.en_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractA primary defect leading to the development of type 2 diabetes is insulin resistance of the glucose transport system in skeletal muscle. One factor known to induce insulin resistance is oxidative stress. A by>product of lipid peroxidation is the reactive aldehyde 4-hydroxynonenal (4-HNE), an oxidant that induces a number of deleterious consequences on cell function. However, the impact of 4-HNE on the glucose transport system in rat slow>twitch skeletal muscle is currently not known. Therefore, we assessed the impact of 4-HNE on insulin signaling factors (IRS-1 protein expression and phosphorylation of Akt Ser473 (pAkt) and AS160 Thr642 (pAS160)) and on glucose transport activity in mammalian slow-twitch muscle. Strips of soleus muscle from lean Zucker rats were incubated with 4-HNE (50 μM) in the absence or presence of insulin (5 mU/ml) for up to 6 hr. Insulin>stimulated glucose transport activity (determined using 2-deoxyglucose uptake) was decreased by 4-HNE at 2 hr (30%), 4 hr (26%), and 6 hr (39%) (all p<0.05). At 2 hr of 4-HNE treatment in the presence of insulin, pAS160 was decreased by 28%, whereas pAkt was only reduced 11% and IRS-1 protein levels were not changed. At 4 hr, pAS160 was decreased by 22%, as was pAkt, and IRS-1 levels were 39% lower than in the control muscles. At 6 hr, pAS160 was 47% lower, pAkt was decreased by 26%, and IRS-1 protein levels were reduced by 51%. Interestingly, IRS-2 protein levels were decreased by 17% only at the 6 hr time point. In summary, these data indicate that the lipid peroxidation end>product and oxidant 4-HNE induces insulin resistance of glucose transport activity in rat slow>twitch skeletal muscle, initially associated with impaired phosphorylation (and therefore reduced activation) of AS160. Longer durations of 4-HNE exposure led to a greater impairment of Akt phosphorylation and to a selective loss of IRS-1 protein. These results provide further support for an important role of oxidative stress in the etiology of skeletal muscle insulin resistance.en_US
dc.typetexten_US
dc.typeElectronic Thesisen_US
thesis.degree.nameB.S.en_US
thesis.degree.levelbachelorsen_US
thesis.degree.disciplineHonors Collegeen_US
thesis.degree.disciplinePhysiologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorHenriksen, Erik-
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