Effects of diabetes on myocardial glucose transport system in rats: Implications for diabetic cardiomyopathy

W. T. Garvey, D. Hardin, M. Juhaszova, Jesus Dominguez

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Abstract

Biochemical mechanisms underlying impaired myocardial glucose utilization in diabetes mellitus have not been elucidated. We studied sarcolemmal vesicles (SL) in control, streptozotocin-induced diabetic (D), and insulin- treated diabetic (Tx) rats and found that 3-O-methylglucose transport rates were decreased 53% in D rats and were normalized by insulin therapy. Immunoblot analyses of SL revealed that GLUT4 glucose transporters were decreased 56% in D and were normal in Tx rats. Thus diminished transport rates could be fully explained by reduced numbers of SL GLUT4 with normal functional activity. To determine whether SL GLUT4 were decreased due to tissue depletion or abnormal subcellular distribution, we measured GLUT4 in total membranes (SL plus intracellular fractions). Total GLUT4 (per mg membrane protein or per DNA) was decreased 45-51% in D [half time = 3.5 days after streptozotocin], and these values were restored to normal in Tx rats. Also, diabetes decreased GLUT4 mRNA levels by 43%, and this effect was reversed by insulin therapy. We conclude that, in diabetes, 1) impaired myocardial glucose utilization is the result of a decrease in glucose transport activity, and 2) transport rates are reduced due to pretranslational suppression of GLUT4 gene expression and can be corrected by insulin therapy, GLUT4 depletion could limit glucose availability under conditions of increased workload and anoxia and could cause myocardial dysfunction.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number3 33-3
StatePublished - 1993

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Diabetic Cardiomyopathies
Insulin
Glucose
Streptozocin
3-O-Methylglucose
Facilitative Glucose Transport Proteins
Workload
Type 1 Diabetes Mellitus
Diabetes Mellitus
Membrane Proteins
Therapeutics
Gene Expression
Messenger RNA
Membranes
DNA

Keywords

  • diabetes mellitus
  • gene expression
  • glucose transporter proteins
  • GLUT4
  • heart
  • insulin resistance
  • myocardium
  • streptozotocin

ASJC Scopus subject areas

  • Physiology

Cite this

Effects of diabetes on myocardial glucose transport system in rats : Implications for diabetic cardiomyopathy. / Garvey, W. T.; Hardin, D.; Juhaszova, M.; Dominguez, Jesus.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 264, No. 3 33-3, 1993.

Research output: Contribution to journalArticle

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