Evidence for rapid "metabolic switching" through lipoprotein lipase occupation of endothelial-binding sites

J Mol Cell Cardiol. 2003 Sep;35(9):1093-103. doi: 10.1016/s0022-2828(03)00205-0.


During diabetes, impaired glucose transport and utilization by the heart switches energy production to exclusive beta-oxidation of fatty acid (FA). In the current study, we examined the contribution of cardiac lipoprotein lipase (LPL) towards providing FA to the diabetic heart. Streptozotocin (STZ) caused an augmentation of LPL activity at the coronary lumen, an effect duplicated by diazoxide (DZ). With DZ, the amplification of LPL at the coronary luminal surface was determined to be exceptionally rapid. Interestingly, unlike DZ, the capability of hearts from STZ animals to maintain this amplified LPL activity was sustained in vitro. This increased enzyme in the hyperglycemic heart is likely unrelated to an increase in the number of capillary endothelial LPL-binding sites. Our data imply that binding sites for LPL in the control rat heart are only partly occupied by the enzyme and diabetes rapidly initiates filling of all of these sites. Phloridzin treatment of STZ animals normalized plasma glucose with no effect on luminal LPL suggesting that the effects of diabetes on LPL are also largely independent of changes in blood glucose. Both 2 and 8 U of insulin normalized plasma glucose in DZ-treated animals but only 8 U reversed DZ-induced augmentation of cardiac luminal LPL. Our data suggest that impaired intracellular glucose utilization allows rapid vectorial transfer of LPL to unoccupied binding sites to supply the diabetic heart with excess FA. The persistence of increased coronary luminal LPL even in a setting of normoglycemia may provide excessive FA to the diabetic heart with deleterious consequences over the long term.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Binding Sites
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / enzymology*
  • Dichloroacetic Acid / pharmacology
  • Endothelial Cells / enzymology*
  • Endothelium, Vascular / enzymology
  • Fatty Acids, Nonesterified / metabolism
  • Gene Expression Regulation, Enzymologic
  • Hyperglycemia / blood
  • Hyperglycemia / metabolism
  • Insulin / administration & dosage
  • Insulin / blood
  • Lipolysis
  • Lipoprotein Lipase / analysis
  • Lipoprotein Lipase / genetics
  • Lipoprotein Lipase / metabolism*
  • Male
  • Malonyl Coenzyme A / analysis
  • Malonyl Coenzyme A / metabolism
  • Milk / enzymology
  • Perfusion
  • Phlorhizin / pharmacology
  • Pyruvate Dehydrogenase Complex / antagonists & inhibitors
  • Pyruvate Dehydrogenase Complex / metabolism
  • Rats
  • Rats, Wistar
  • Streptozocin
  • Time Factors


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • Pyruvate Dehydrogenase Complex
  • Malonyl Coenzyme A
  • Streptozocin
  • Dichloroacetic Acid
  • Phlorhizin
  • Lipoprotein Lipase