High dietary sucrose triggers hyperinsulinemia, increases myocardial β-oxidation, reduces glycolytic flux and delays post-ischemic contractile recovery

Gonsolin, D.; Couturier, Karine; Garait, Blandine; Rondel, Stéphanie; Novel-Chate, Valérie; Peltier, Sébastien; Faure, Patrice; Gachon, Pierre; Boirie‌, Yves; Kériel, Christiane; Favier, R.; Pepe, Salvatore; Demaison, Luc; Leverve, Xavier

doi:10.1007/s11010-006-9291-7

Cited by 19 publications

(12 citation statements)

References 57 publications

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“…Indeed, a relationship between reperfusion contractile function and myocardial glucose flux rates has been noted in insulin-resistant rats (12). Moreover, insulin-stimulated myocardial glycolysis is suppressed by fatty acids (10) and, as indicated by the present and prior studies (1,20), the exposure of the heart to fatty acids considerably increases myocardial injury in response to ischemia-reperfusion.…”

Section: Discussionmentioning

confidence: 62%

Myocardial susceptibility to ischemic-reperfusion injury in a prediabetic model of dietary-induced obesity

Toit

Smith²,

Muller³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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We assessed the myocardial susceptibility to ischemic-reperfusion injury in obese rat hearts in the absence and the presence of predicted circulating concentrations of insulin and fatty acids. Feeding rats a high-calorie diet resulted in increases in body weight, visceral fat content, cardiac hypertrophy, plasma insulin, nonesterified free fatty acid, and triglyceride concentrations. In the absence of both insulin and fatty acids in the coronary perfusate, the hearts of obese rats developed an increased infarct size (41.9 +/- 1.9% for obese vs. 22.9 +/- 2.3% for control, P < 0.05) and a reduced percent recovery of aortic output (4.2 +/- 4.2% for obese vs. 27.7 +/- 3.4% for controls, P < 0.05) after coronary artery occlusion and reperfusion. In the presence of insulin in the coronary perfusate, a cardioprotective effect was noted in both groups, an action that was greater in hearts from obese compared with control rats and which abolished the obesity-induced changes in infarct size (13.8 +/- 1.2% for controls vs. 21.0 +/- 1.6% for obese), and percent recovery of aortic output (60.2 +/- 4.7% for controls vs. 45.7 +/- 9.4% for obese). Fatty acids (0.7 mM, control; and 1.5 mM, obese) added to the coronary perfusate with in vivo concentrations of insulin dramatically increased infarct size (48.2 +/- 3.1% for obese, and 37.5 +/- 2.7% for control; P < 0.05 vs. without fatty acids) and decreased percent aortic output recovery (control, 10.4 +/- 5.2%, and obese 7.8 +/- 3.5%; P < 0.05 vs. without fatty acids) in both groups to similar values. In conclusion, in obesity, the impact of an increased susceptibility of the myocardium to ischemic-reperfusion injury on myocardial injury is likely to be overshadowed by the comparatively greater roles played by predicted increases in circulating insulin and fatty acids found in vivo. These data support the notion that adiposity per se is unlikely to be a valuable predictor of outcomes in ischemic-reperfusion injury.

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Section: Discussionmentioning

confidence: 62%

Myocardial susceptibility to ischemic-reperfusion injury in a prediabetic model of dietary-induced obesity

Toit

Smith²,

Muller³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Many studies have shown that high fat and/or high sucrose diets induces insulin resistance in rodents (17,33,37,38). The mechanisms by which high fat and/or high sucrose diets cause insulin resistance are not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Intake of Sucrose-sweetened Water Induces Insulin Resistance and Exacerbates Memory Deficits and Amyloidosis in a Transgenic Mouse Model of Alzheimer Disease

Cao

Lewis

et al. 2007

Journal of Biological Chemistry

303

217

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Compelling evidence indicates that excess consumption of sugar-sweetened beverages plays an important role in the epidemic of obesity, a major risk factor for type 2 diabetes mellitus. Type 2 diabetes mellitus has been associated with a higher incidence of Alzheimer disease (AD). High fat diets promote ADlike pathology in mice. It is not known whether consumption of excess sugar as in calorically sweetened beverages with an otherwise normal diet affects the development of AD. In the present study, we provided 10% sucrose-sweetened water to a transgenic mouse model of AD with a normal rodent diet. Compared with the control mice with no sucrose added in the water, the sucrose group gained more body weight and developed glucose intolerance, hyperinsulinemia, and hypercholesterolemia. These metabolic changes were associated with the exacerbation of memory impairment and a 2-3-fold increase in insoluble amyloid-␤ protein levels and deposition in the brain. We further showed that the levels of expression and secretase-cleaved products of amyloid-␤ precursor protein were not affected by sucrose intake. The steady-state levels of insulin-degrading enzyme did not change significantly, whereas there was a 2.5-fold increase in brain apoE levels. Therefore, we concluded that the up-regulation of apoE accelerated the aggregation of A␤, resulting in the exacerbation of cerebral amyloidosis in sucrose-treated mice. These data underscore the potential role of dietary sugar in the pathogenesis of AD and suggest that controlling the consumption of sugar-sweetened beverages may be an effective way to curtail the risk of developing AD.Added sugars, mainly sucrose and high fructose corn syrup, are major components of a modern human diet. Compelling evidence indicates that excess consumption of sweet foods, particularly sugar-sweetened beverages, plays an important role in the epidemic of obesity around the world (1). In the United States, the percentage of children who are overweight has doubled, and the percentage of teenagers who are overweight has tripled (2, 3). Overweight children are at an increased risk to become obese adults (4). Even moderate obesity can contribute to chronic metabolic abnormalities leading to type 2 diabetes mellitus (5) characterized by glucose intolerance and hyperinsulinemia.Alzheimer disease (AD) 2 is a progressive neurodegenerative disease characterized clinically by progressive cognitive impairment. Pathological hallmarks of the AD brain include intracellular neurofibrillary tangles and deposits of aggregated amyloid-␤ protein (A␤) in neuritic plaques and cerebral vessels. The pathogenic mechanisms that lead to the development of AD, however, are not fully understood. One of the main hypotheses is that ␤-amyloidosis (production and deposition of A␤) plays a crucial role in the pathogenesis of AD (6). A␤ (39 -43 amino acids) is derived from a large transmembrane glycoprotein, amyloid-␤ precursor protein (APP), via proteolytic processing by secretases (6). This hypothesis is supported by discoveries of...

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“…The cause for these complications in diabetic patients is the greater sensitivity of diabetic hearts to ischemia-reperfusion injury. This has been linked to impaired Akt signaling and GLUT4 trafficking, as well as mitochondrial dysfunction [5], [6], [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Loss of Intralipid®- but Not Sevoflurane-Mediated Cardioprotection in Early Type-2 Diabetic Hearts of Fructose-Fed Rats: Importance of ROS Signaling

et al. 2014

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BackgroundInsulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury.MethodsEarly type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1%) was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%) served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained.ResultsIntralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3.ConclusionsEarly type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection.

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High dietary sucrose triggers hyperinsulinemia, increases myocardial β-oxidation, reduces glycolytic flux and delays post-ischemic contractile recovery

Cited by 19 publications

References 57 publications

Myocardial susceptibility to ischemic-reperfusion injury in a prediabetic model of dietary-induced obesity

Myocardial susceptibility to ischemic-reperfusion injury in a prediabetic model of dietary-induced obesity

Intake of Sucrose-sweetened Water Induces Insulin Resistance and Exacerbates Memory Deficits and Amyloidosis in a Transgenic Mouse Model of Alzheimer Disease

Loss of Intralipid®- but Not Sevoflurane-Mediated Cardioprotection in Early Type-2 Diabetic Hearts of Fructose-Fed Rats: Importance of ROS Signaling

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