Streptozotocin diabetes increases mRNA expression of ketogenic enzymes in the rat heart

George Cook, Eduard N. Lavrentyev, Kevin Pham, Edwards Park

Research output: Contribution to journalArticle

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Abstract

Background Diabetic cardiomyopathy develops in insulin-dependent diabetic patients who have no hypertension, cardiac hypertrophy or vascular disease. Diabetes increases cardiac fatty acid oxidation, but cardiac hypertrophy limits fatty acid oxidation. Here we examined effects of diabetes on gene expression in rat hearts. Methods We used oligonucleotide microarrays to examine effects of insulindependent diabetes in the rat heart. RTQ PCR confirmed results of microarrays. Specific antibodies were used to examine changes in the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). Results A surprising result of diabetes was increased mRNA encoding all enzymes of the ketone body synthesis pathway. Increased mRNA expression for these enzymes was confirmed by RTQ PCR. The mRNA encoding HMGCS2, the rate-controlling enzyme, was 27 times greater in diabetic hearts. Total HMGCS2 protein increased 8-fold in diabetic hearts, but no difference was found in HMGCS2 protein in control vs. diabetic liver. Conclusions Insulin-dependent diabetes induced the enzymes of ketone body synthesis in the heart, including HMGCS2, as well as increasing enzymes of fatty acid oxidation. General significance The mammalian heart does not export ketone bodies to other tissues, but rather is a major consumer of ketone bodies. Induction of HMGCS2, which is normally expressed only in the fetal and newborn heart, may indicate an adaptation by the heart to combat “metabolic inflexibility” by shifting the flux of excess intramitochondrial acetyl-CoA derived from elevated fatty acid oxidation into ketone bodies, liberating free CoA to balance the acetyl-CoA/CoA ratio in favor of increased glucose oxidation through the pyruvate dehydrogenase complex.

Original languageEnglish (US)
Pages (from-to)307-312
Number of pages6
JournalBiochimica et Biophysica Acta - General Subjects
Volume1861
Issue number2
DOIs
StatePublished - Feb 1 2017

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Experimental Diabetes Mellitus
Streptozocin
Medical problems
Ketone Bodies
Rats
Messenger RNA
Enzymes
Fatty Acids
Oxidation
Acetyl Coenzyme A
Cardiomegaly
Coenzyme A
Microarrays
Diabetic Cardiomyopathies
Insulin
Pyruvate Dehydrogenase Complex
Fetal Heart
Polymerase Chain Reaction
Oligonucleotide Array Sequence Analysis
Vascular Diseases

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Streptozotocin diabetes increases mRNA expression of ketogenic enzymes in the rat heart. / Cook, George; Lavrentyev, Eduard N.; Pham, Kevin; Park, Edwards.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1861, No. 2, 01.02.2017, p. 307-312.

Research output: Contribution to journalArticle

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