Myocardial metabolism in insulin-deficient diabetic humans without coronary artery disease

A. Avogaro, R. Nosadini, A. Doria, P. Fioretto, M. Velussi, C. Vigorito, L. Sacca, G. Toffolo, C. Cobelli, R. Trevisan, E. Duner, R. Razzolini, F. Rengo, G. Crepaldi

Research output: Contribution to journalArticlepeer-review

Abstract

Eleven insulin-dependent diabetes mellitus (IDDM) patients with angiographically normal coronary arteries and a normal hemodynamic response to an echocardiographic-dipyridamole test and 12 normal controls were studied at rest and after atrial pacing simultaneously sampling arterial and coronary sinus blood. In IDDM patients, despite hyperglycemia [10.0 ± 2.0 (SE) mmol/l], myocardial glucose uptake was slightly lower than in controls. This process was significantly activated in both groups during atrial pacing. The isotopically calculated net flux of lactate across myocardium, in agreement with the net balance value based on unlabeled lactate-pyruvate arteriovenous differences, showed a net uptake in controls (3.5 ± 0.6 μmol · min-1 · 1.73 m-2) and a net release in IDDM (12.4 ± 2.6; P <0.01). Atrial pacing stimulated lactate uptake in both groups. Myocardial uptake of ketone bodies was significantly higher in IDDM (37.0 ± 6.3 μmol · min-1 · 1.73 m-2) than in controls (10.1 ± 3.4 μmol · min-1 · 1.73 m-2; P <0.01). Free fatty acids uptake was also significantly greater in IDDM than in controls (44.1 ± 7.0 vs. 24.1 ± 5.1 μmol · min-1 · 1.73 m-2; P <0.01). Alanine and branched amino acids were released by diabetic but not by control hearts at rest. The normalization of blood glucose concentrations restored normal patterns of lactate and ketone body kinetics across diabetic myocardium. In conclusion, 1) at rest, myocardial lactate and amino acid uptake is markedly impaired in IDDM without coronary artery disease, and 2) the metabolic abnormalities of the diabetic myocardium are not a primary phenomenon but rather a consequence of hypoinsulinemia and hyperglycemia because insulin administration, resulting in euglycemia, restored normal patterns of cardiac metabolism.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume258
Issue number4 21-4
Publication statusPublished - 1990

Keywords

  • diabetes
  • free fatty acids
  • ketone body
  • lactate

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

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