Diabetic Cardiomyopathy in Zucker Diabetic Fatty Rats: the Forgotten Right Ventricle

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2010 Jun 17

PMID 20550678

Citations 27

Authors

Charissa E van den Brom

Joanna W A M Bosmans

Ronald Vlasblom

Louis M Handoko

Marc C Huisman

Mark Lubberink

Carla F M Molthoff

Adriaan A Lammertsma

Margriet D Ouwens

Michaela Diamant

Christa Boer

Affiliations

Soon will be listed here.

Abstract

Background: In patients with myocardial infarction or heart failure, right ventricular (RV) dysfunction is associated with death, shock and arrhythmias. In patients with type 2 diabetes mellitus, structural and functional alterations of the left ventricle (LV) are highly prevalent, however, little is known about the impact of diabetes on RV characteristics. The purpose of the present study was to investigate whether LV changes are paralleled by RV alterations in a rat model of diabetes.

Methods: Zucker diabetic fatty (ZDF) and control (ZL) rats underwent echocardiography and positron emission tomography (PET) scanning using [18F]-2-fluoro-2-deoxy-D-glucose under hyperinsulinaemic euglycaemic clamp conditions. Glucose, insulin, triglycerides and fatty acids were assessed from trunk blood. Another group of rats received an insulin or saline injection to study RV insulin signaling.

Results: ZDF rats developed hyperglycaemia, hyperinsulinaemia and dyslipidaemia (all p < 0.05). Echocardiography revealed depressed LV fractional shortening and tricuspid annular plane systolic excursion (TAPSE) in ZDF vs. ZL rats (both p < 0.05). A decrease in LV and RV insulin-mediated glucose utilisation was found in ZDF vs. ZL rats (both p < 0.05). LV associated with RV with respect to systolic function (r = 0.86, p < 0.05) and glucose utilisation (r = 0.74, p < 0.05). TAPSE associated with RV MRglu (r = 0.92, p < 0.05) and M-value (r = 0.91, p < 0.0001) and RV MRglu associated with M-value (r = 0.77, p < 0.05). Finally, reduced RV insulin-stimulated phosphorylation of Akt was found in ZDF vs. ZL (p < 0.05).

Conclusions: LV changes were paralleled by RV alterations in insulin-stimulated glucose utilisation and RV systolic function in a rat model of diabetes, which may be attributed to ventricular interdependence as well as to the uniform effect of diabetes. Since diabetic patients are prone to develop diabetic cardiomyopathy and myocardial ischaemia, it might be suggested that RV dysfunction plays a central role in cardiac abnormalities in this population.

Citing Articles

Impact of diabetes mellitus on right ventricular dysfunction and ventricular interdependence in hypertensive patients with heart failure with reduced ejection fraction assessed via 3.0 T cardiac MRI.

Zhang G, Shi R, Li X, Yan W, Xu H, Li Y Cardiovasc Diabetol. 2024; 23(1):375.

PMID: 39443983 PMC: 11515597. DOI: 10.1186/s12933-024-02472-z.

Myocardial Calcium Handling in Type 2 Diabetes: A Novel Therapeutic Target.

Dattani A, Singh A, McCann G, Gulsin G J Cardiovasc Dev Dis. 2024; 11(1).

PMID: 38248882 PMC: 10817027. DOI: 10.3390/jcdd11010012.

Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery.

Gao S, Liu X, Li T, Chen L, Feng Y, Wang Y Acta Pharmacol Sin. 2023; 45(1):23-35.

PMID: 37644131 PMC: 10770177. DOI: 10.1038/s41401-023-01152-0.

Age and Sex Differences in Heart Failure With Preserved Ejection Fraction.

Kobak K, Zarzycka W, Chiao Y Front Aging. 2022; 3:811436.

PMID: 35821846 PMC: 9261310. DOI: 10.3389/fragi.2022.811436.

Heart failure in diabetes.

Jankauskas S, Kansakar U, Varzideh F, Wilson S, Mone P, Lombardi A Metabolism. 2021; 125:154910.

PMID: 34627874 PMC: 8941799. DOI: 10.1016/j.metabol.2021.154910.

References

Kosmala W, Colonna P, Przewlocka-Kosmala M, Mazurek W . Right ventricular dysfunction in asymptomatic diabetic patients. Diabetes Care. 2004; 27(11):2736-8. DOI: 10.2337/diacare.27.11.2736. View

van den Brom C, Huisman M, Vlasblom R, Boontje N, Duijst S, Lubberink M . Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography. Cardiovasc Diabetol. 2009; 8:39. PMC: 2722582. DOI: 10.1186/1475-2840-8-39. View

Movahed M, Milne N . Presence of biventricular dysfunction in patients with type II diabetes mellitus. Congest Heart Fail. 2007; 13(2):78-80. DOI: 10.1111/j.1527-5299.2007.888138.x. View

Rytter L, Troelsen S, Beck-Nielsen H . Prevalence and mortality of acute myocardial infarction in patients with diabetes. Diabetes Care. 1985; 8(3):230-4. DOI: 10.2337/diacare.8.3.230. View

Golfman L, Wilson C, Sharma S, Burgmaier M, Young M, Guthrie P . Activation of PPARgamma enhances myocardial glucose oxidation and improves contractile function in isolated working hearts of ZDF rats. Am J Physiol Endocrinol Metab. 2005; 289(2):E328-36. DOI: 10.1152/ajpendo.00055.2005. View

Di Salvo T, Mathier M, Semigran M, Dec G . Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol. 1995; 25(5):1143-53. DOI: 10.1016/0735-1097(94)00511-n. View

Slot J, Geuze H, Gigengack S, James D, Lienhard G . Translocation of the glucose transporter GLUT4 in cardiac myocytes of the rat. Proc Natl Acad Sci U S A. 1991; 88(17):7815-9. PMC: 52394. DOI: 10.1073/pnas.88.17.7815. View

Fang Z, Prins J, Marwick T . Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev. 2004; 25(4):543-67. DOI: 10.1210/er.2003-0012. View

An D, Rodrigues B . Role of changes in cardiac metabolism in development of diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2006; 291(4):H1489-506. DOI: 10.1152/ajpheart.00278.2006. View

10.

Mehta S, Eikelboom J, Natarajan M, Diaz R, Yi C, Gibbons R . Impact of right ventricular involvement on mortality and morbidity in patients with inferior myocardial infarction. J Am Coll Cardiol. 2001; 37(1):37-43. DOI: 10.1016/s0735-1097(00)01089-5. View

11.

Pelzer T, Jazbutyte V, Arias-Loza P, Segerer S, Lichtenwald M, Law M . Pioglitazone reverses down-regulation of cardiac PPARgamma expression in Zucker diabetic fatty rats. Biochem Biophys Res Commun. 2005; 329(2):726-32. DOI: 10.1016/j.bbrc.2005.02.029. View

12.

de Groote P, Millaire A, Nugue O, Marchandise X, DUCLOUX G, Lablanche J . Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure. J Am Coll Cardiol. 1998; 32(4):948-54. DOI: 10.1016/s0735-1097(98)00337-4. View

13.

Kosmala W, Przewlocka-Kosmala M, Mazurek W . Subclinical right ventricular dysfunction in diabetes mellitus--an ultrasonic strain/strain rate study. Diabet Med. 2007; 24(6):656-63. DOI: 10.1111/j.1464-5491.2007.02101.x. View

14.

Karamitsos T, Karvounis H, Dalamanga E, Papadopoulos C, Didangellos T, Karamitsos D . Early diastolic impairment of diabetic heart: the significance of right ventricle. Int J Cardiol. 2006; 114(2):218-23. DOI: 10.1016/j.ijcard.2006.02.003. View

15.

Handoko M, Schalij I, Kramer K, Sebkhi A, Postmus P, van der Laarse W . A refined radio-telemetry technique to monitor right ventricle or pulmonary artery pressures in rats: a useful tool in pulmonary hypertension research. Pflugers Arch. 2007; 455(5):951-9. PMC: 2137943. DOI: 10.1007/s00424-007-0334-z. View

16.

Ouwens D, Diamant M, Fodor M, Habets D, Pelsers M, El Hasnaoui M . Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification. Diabetologia. 2007; 50(9):1938-1948. PMC: 2039861. DOI: 10.1007/s00125-007-0735-8. View

17.

Shoghi K, Gropler R, Sharp T, Herrero P, Fettig N, Su Y . Time course of alterations in myocardial glucose utilization in the Zucker diabetic fatty rat with correlation to gene expression of glucose transporters: a small-animal PET investigation. J Nucl Med. 2008; 49(8):1320-7. PMC: 2857655. DOI: 10.2967/jnumed.108.051672. View

18.

Mittal S . Right ventricular functions in patients with type 2 diabetes below 50 years. J Assoc Physicians India. 2007; 55:599-600. View

19.

Ouwens D, Boer C, Fodor M, de Galan P, Heine R, Maassen J . Cardiac dysfunction induced by high-fat diet is associated with altered myocardial insulin signalling in rats. Diabetologia. 2005; 48(6):1229-37. DOI: 10.1007/s00125-005-1755-x. View