Aging is associated with myocardial insulin resistance and mitochondrial dysfunction.

Aging is associated with myocardial insulin resistance and mitochondrial dysfunction. Research Abstract Details 

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Aging is associated with myocardial insulin resistance and mitochondrial dysfunction. Abstract Text:

Siva Bhashyam,Pratik Parikh,Hakki Bolukoglu,Alexander H Shannon,James H Porter,You-Tang Shen,Richard P Shannon,Siva Bhashyam,Pratik Parikh,Hakki Bolukoglu,Alexander H Shannon,James H Porter,You-Tang Shen,Richard P Shannon,

Aging is associated with insulin resistance, often attributable to obesity and inactivity. Recent evidence suggests that skeletal muscle insulin resistance in aging is associated with mitochondrial alterations. Whether this is true of the senescent myocardium is unknown. Twelve young (Y, 4 years old) and 12 old (O, 11 years old) dogs, matched for body mass, were instrumented with left-ventricular pressure gauges, aortic and coronary sinus catheters, and flow probes on left circumflex artery. Before surgery, all dogs participated in a 6-wk exercise program. Dogs underwent measurements of hemodynamics and plasma substrates before and during a 2-h hyperinsulinemic-euglycemic clamp to measure whole body and myocardial glucose and nonesterified fatty acid uptake. Following the protocol, myocardial and skeletal samples were obtained to measure components of the insulin-signaling cascade and mitochondrial structure. There was no difference in plasma glucose (Y, 90 +/- 4 mg/dl; O, 87 +/- 4 mg/dl), but old dogs had higher (P < 0.02) nonesterified fatty acids (Y, 384 +/- 48 micromol/l; O, 952 +/- 97 micromol/l) and plasma insulin (Y, 39 +/- 11 pmol/l; O, 108 +/- 18 pmol/l). Old dogs had impaired total body glucose disposition (Y, 11.5 +/- 1 mg x kg(-1) x min(-1); O, 8.0 +/- 0.5 mg x kg(-1) x min(-1); P < 0.05) and insulin-stimulated myocardial glucose uptake (Y, 3.5 +/- 0.3 mg x min(-1) x g(-1); O, 1.8 +/- 0.3 mg x min(-1) x g(-1); P < 0.05). The impaired insulin action was associated with altered insulin signaling and glucose transporter (GLUT4) translocation. There were myocardial mitochondrial structural changes observed in association with decreased expression of uncoupling protein-3. Aging is associated with both whole body and myocardial insulin resistance, independent of obesity and inactivity, but involving altered mitochondrial structure and impaired cellular insulin action.

Aging is associated with myocardial insulin resistance and mitochondrial dysfunction. Publishing Authors By Initials

S Bhashyam,P Parikh,H Bolukoglu,AH Shannon,JH Porter,YT Shen,RP Shannon,S Bhashyam,P Parikh,H Bolukoglu,AH Shannon,JH Porter,YT Shen,RP Shannon,

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Aging is associated with myocardial insulin resistance and mitochondrial dysfunction. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: American journal of physiology. Heart and circulat

VOLUME: 293

Page Numbers: H3063-71

Journal Abbreviation: Am. J. Physiol. Heart Circ. Ph

ISSN: 0363-6135

DAY: 14

MONTH: 09

YEAR: 2007

Aging is associated with myocardial insulin resistance and mitochondrial dysfunction. Information

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LANGUAGE: eng

NlmUniqueID: 100901228

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Grant and Affiliation Information for Aging is associated with myocardial insulin resistance and mitochondrial dysfunction.

AFFILIATION: Department of Medicine, Allegheny General Hospital, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Country: United States

AGENCY: United States NIDA

GRANT: DA-104080

ACRONYM: DA

MEDLINETA: Am J Physiol Heart Circ Physio

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