Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

Frank C. Howarth, Muhammad A. Qureshi, Zahra H.H. Sobhy, Khatija Parekh, Salem R.R.K.D. Yammahi, Thomas E. Adrian, Ernest Adeghate

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17 Citations (Scopus)

Abstract

Given the clinical prevalence of type 2 diabetes and obesity and their association with high mortality linked to cardiovascular disease, the aim of the study was to investigate the effects of feeding type 2 diabetic Goto-Kakizaki (GK) rats either high- or low-fat diets on cardiomyocyte structure and function. The GK rats were fed either a high-fat diet (HFD) or a low-fat diet (LFD) from the age of 2 months for a period of 7 months. The GK-HFD rats gained more weight, ate less food and drank less water compared with GK-LFD rats. At 7 months, non-fasting blood glucose was higher in GK-LFD (334 ± 35 mg dl-1) compared with GK-HFD rats (235 ± 26 mg dl-1). Feeding GK rats with a HFD had no significant effect on glucose clearance following a glucose challenge. Time-to-peak (tpeak) shortening was reduced in myocytes from GK-HFD (131.8 ± 2.1 ms) compared with GK-LFD rats (144.5 ± 3.0 ms), and time-to-half (t1/2) relaxation of shortening was also reduced in myocytes from GK-HFD (71.7 ± 6.9 ms) compared with GK-LFD rats (86.1 ± 3.6 ms). The HFD had no significant effect on the amplitude of shortening. The HFD had no significant effect ontpeak,t1/2 decay, amplitude of the Ca2+ transient, myofilament sensitivity to Ca2+, sarcoplasmic reticulum Ca2+ content, fractional release of Ca2+ and the rate of Ca2+ uptake. Structurally, ventricular myocytes from GK-HFD rats showed extensive mitochondrial lesions, including swelling, loss of cristae, and loss of inner and outer membranes, resulting in gross vacuolarization and deformation of ventricular mitochondria with a subsequent reduction in mitochondrial density. Expression of genes encoding various L-type Ca2+ channel proteins (Cacnb2) and cardiac muscle proteins (Myl2 and Atp2a1) were downregulated in GK-HFD compared with GK-LFD rats. Structural lesions and changed expression of genes encoding various cardiac muscle proteins might partly underlie the altered time course of myocyte shortening and relaxation in myocytes from GK-HFD compared with GK-LFD rats.

Original languageEnglish
Pages (from-to)765-777
Number of pages13
JournalExperimental Physiology
Volume96
Issue number8
DOIs
Publication statusPublished - Aug 2011

ASJC Scopus subject areas

  • Physiology
  • Nutrition and Dietetics
  • Physiology (medical)

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