Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance

P. H. McNulty, Rita Jean Louard, L. I. Deckelbaum, B. L. Zaret, L. H. Young

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Background: Insulin resistance, hyperinsulinemia, and myocardial hypertrophy frequently coexist in patients. Whether hyperinsulinemia directly affects myocardial protein metabolism in humans has not been examined, however. To test the hypothesis that hyperinsulinemia is anabolic for human heart protein, we examined the effects of insulin infusion on myocardial protein synthesis, degradation, and net balance in patients with ischemic heart disease. Methods and Results: Eleven men (aged 57±3 years) with coronary artery disease who had fasted for 12 to 16 hours received a constant infusion of insulin (50 mU · m-2 · min-1) while plasma concentrations of glucose and amino acids were kept constant. Rates of myocardial protein synthesis, degradation, and net balance were estimated from steady state extraction and isotopic dilution of L-[ring-2,6-3H]phenylalanine across the heart basally and 90 minutes into infusion. Subjects had elevated fasting plasma insulin concentrations (173±21 pmol/L) and used little exogenous glucose during insulin infusion, suggesting resistance to the effects of insulin on whole-body carbohydrate metabolism. Basally, myocardial protein degradation, as estimated by phenylalanine release (133±28 nmol/min), exceeded protein synthesis, estimated by phenylalanine uptake (31±15 nmol/min), resulting in net negative phenylalanine balance (-102±17 nmol/min). Insulin infusion reduced myocardial protein degradation by 80% but did not affect protein synthesis, returning net phenylalanine balance to neutral. Conclusions: Acute hyperinsulinemia markedly suppresses myocardial protein degradation in patients with cardiovascular disease who are resistant to its effects on whole-body glucose metabolism. This antiproteolytic action represents a potential mechanism by which hyperinsulinemia could contribute to the development of myocardial hypertrophy in patients with cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)2151-2156
Number of pages6
JournalCirculation
Volume92
Issue number8
StatePublished - 1995
Externally publishedYes

Fingerprint

Disease Resistance
Hyperinsulinism
Proteolysis
Insulin Resistance
Phenylalanine
Cardiovascular Diseases
Insulin
Glucose
Hypertrophy
Proteins
Carbohydrate Metabolism
Myocardial Ischemia
Coronary Artery Disease
Fasting
Amino Acids

Keywords

  • hypertension
  • hypertrophy
  • insulin
  • myocardium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance. / McNulty, P. H.; Louard, Rita Jean; Deckelbaum, L. I.; Zaret, B. L.; Young, L. H.

In: Circulation, Vol. 92, No. 8, 1995, p. 2151-2156.

Research output: Contribution to journalArticle

McNulty, P. H. ; Louard, Rita Jean ; Deckelbaum, L. I. ; Zaret, B. L. ; Young, L. H. / Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance. In: Circulation. 1995 ; Vol. 92, No. 8. pp. 2151-2156.
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