High dietary sucrose triggers hyperinsulinemia, increases myocardial beta-oxidation, reduces glycolytic flux and delays post-ischemic contractile recovery.
Although the causal relationship between insulin resistance (IR) and hypertension is not fully resolved, the importance of IR in cardiovascular dysfunction is recognized. As IR may follow excess sucrose or fructose diet, the aim of this study was to test whether dietary starch substitution with sucrose results in myocardial dysfunction in energy substrate utilization and contractility during normoxic and post-ischemic conditions. Forty-eight male Wistar rats were randomly allocated to three diets, differing only in their starch to sucrose (S) ratio (13, 2 and 0 for the Low S, Middle S and High S groups, respectively), for 3 weeks. Developed pressure and rate x pressure product (RPP) were determined in Langendorff mode-perfused hearts. After 30 min stabilization, hearts were subjected to 25 min of total normothermic global ischemia, followed by 45-min reperfusion. Oxygen consumption, beta-oxidation rate (using 1-13C hexanoate and Isotopic Ratio Mass Spectrometry of CO2 produced in the coronary effluent) and flux of non-oxidative glycolysis were also evaluated. Although fasting plasma glucose levels were not affected by increased dietary sucrose, high sucrose intake resulted in increased plasma insulin levels, without significant rise in plasma triglyceride and free fatty acid concentrations. Sucrose-rich diet reduced pre-ischemic baseline measures of heart rate, RPP and non-oxidative glycolysis. During reperfusion, post-ischemic recovery of RPP was impaired in the Middle S and High S groups, as compared to Low S, mainly due to delayed recovery of developed pressure, which by 45 min of reperfusion eventually resumed levels matching Low S. At the start of reperfusion, delayed post-ischemic recovery of contractile function was accompanied by: (i) reduced lactate production; (ii) decreased lactate to pyruvate ratio; (iii) increased beta-oxidation; and (iv) depressed metabolic efficiency. In conclusion, sucrose rich-diet increased plasma insulin levels, in intact rat, and increased cardiac beta-oxidation and coronary flow-rate, but reduced glycolytic flux and contractility during normoxic baseline function of isolated perfused hearts. Sucrose rich-diet impaired early post-ischemic recovery of isolated heart cardiac mechanical function and further augmented cardiac beta-oxidation but reduced glycolytic and lactate flux.
Gonsolin
D
D
Laboratoire de Bioénergétique Fondamentale et Appliquée, INSERM E221, Université J. Fourier, BP 53, 38041, Grenoble cedex 09, France.
Couturier
K
K
Garait
B
B
Rondel
S
S
Novel-Chaté
V
V
Peltier
S
S
Faure
P
P
Gachon
P
P
Boirie
Y
Y
Keriel
C
C
Favier
R
R
Pepe
S
S
Demaison
L
L
Leverve
X
X
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D019422:Dietary Sucrose / Q000008:administration & dosage* / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D006946:Hyperinsulinism / Q000473:pathology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000473:pathology*; D015428:Myocardial Reperfusion Injury; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D019422:Dietary Sucrose; D007328:Insulin; D008055:Lipids; D014280:Triglycerides; D019344:Lactic Acid; D019289:Pyruvic Acid