title: Hyperinsulinemia inhibits myocardial protein degradation in patients with cardiovascular disease and insulin resistance.
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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, Veterans Affairs Medical Center, West Haven, Conn 06516, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: McNulty
authors.forename: R J
authors.initials: RJ
authors.lastname: Louard
authors.forename: L I
authors.initials: LI
authors.lastname: Deckelbaum
authors.forename: B L
authors.initials: BL
authors.lastname: Zaret
authors.forename: L H
authors.initials: LH
authors.lastname: Young
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009124:Muscle Proteins; D010649:Phenylalanine; D005947:Glucose