Mechanisms underlying depressed Na+/Ca2+ exchanger activity in the diabetic heart

Stephen W. Schaffer, Cherry Ballard-Croft, Scott Boerth, Simon N. Allo

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67 Scopus citations


Objectives: Depression in Na+/Ca2+ exchanger activity is an important factor in the development of the diabetic cardiomyopathy. Since the mechanism underlying this depression remains unknown, the aim of this study was to determine the contribution of hyperglycemia and insulinopenia towards the observed impairment in Na+/Ca2+ exchanger activity. Methods: Non-insulin- dependent diabetes was induced in neonatal Wistar rats by injection of 90 mg/kg streptozotocin. Na+/Ca2+ exchange in sarcolemmal vesicles and isolated cardiomyocytes was determined by Na+-dependent 45Ca2+ transport. To assess the role of insulin deficiency and hyperglycemia on Na+/Ca2+ exchanger activity, neonatal cardiomyocytes were incubated for 3 days in media containing either 5 mM glucose and 56 U/I insulin (Control), 30 mM glucose and 56 U/I insulin (High glucose) or 5 mM glucose and 0 insulin (Insulin deficiency). Since hyperglycemia has been shown to affect protein kinase C activity, Ca2+-dependent isoforms of protein kinase C were examined in non-diabetic and diabetic heart using hydroxylapatite chromatography. Also examined was Na+/Ca2+ exchanger mRNA levels in diabetic and non-diabetic hearts using Northern slot blot analysis. Results: Acute insulin produced a dose-dependent increase in Na+/Ca2+ exchanger activity, which was dramatically attenuated in diabetic membrane. Myocytes incubated in media containing 30 mM glucose exhibited a 33% reduction in Na+/Ca2+ exchanger activity, while insulinopenia reduced activity by 63%. Exchanger mRNA levels of the diabetic heart were normal; however, diabetes was associated with major changes in protein kinase C activity. Conclusions: Reduced Na+/Ca2+ exchanger activity resulting from diabetes, hyperglycemia or insulinopenia may be related to changes in protein kinase C activity, but is not caused by altered expression of the transporter.

Original languageEnglish
Pages (from-to)129-136
Number of pages8
JournalCardiovascular Research
Issue number1
StatePublished - Apr 1997


  • Cardiomyopalty
  • Diabetes
  • Na/Ca exchange
  • Protein kinase C
  • Rat
  • Vennicular myocytes

ASJC Scopus subject areas

  • General Medicine


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