Cardiac lipoprotein lipase: metabolic basis for diabetic heart disease.
The heart has a limited potential to synthesize fatty acid (FA), and, therefore, FA is supplied from several sources: lipolysis of endogenous cardiac triglyceride (TG) stores or from exogenous sources in the blood. Lipoprotein lipase (LPL), synthesized in cardiomyocytes, catalyzes the breakdown of the TG component of lipoproteins to provide FA to the heart. It is the vascular endothelial-bound LPL that determines the rate of plasma TG clearance, and, hence, it is also called heparin-releasable (HR) "functional" LPL. Functional LPL is regulated by numerous dietary and hormonal factors and is sensitive to pathophysiological alterations like those observed during diabetes. In this condition, absolute or relative lack of insulin impairs cardiac glucose transport and oxidation, resulting in FA becoming the preferred means of energy supply. To make available this increased requirement of the heart for FA, the diabetic heart upregulates its luminal LPL activity by posttranslational mechanisms. Chronically elevated cardiac LPL can result in abnormal FA supply and utilization by the heart tissue that could potentially initiate and sustain cardiac dysfunction during diabetes. As effective blood glucose control is difficult during diabetes, it is conceivable that a parallel increase in functional cardiac LPL activity may predispose people with diabetes to premature death from cardiac disease. By gaining more insight into the initial metabolic processes in the diabetic heart, we can attempt to piece together a part of the cascade of events leading to diabetic heart disease.
Pulinilkunnil
Thomas
T
Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Rodrigues
Brian
B
D001786:Blood Glucose / Q000378:metabolism; D048909:Diabetes Complications / Q000201:enzymology*; D005227:Fatty Acids / Q000378:metabolism; D006331:Heart Diseases / Q000201:enzymology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D014280:Triglycerides / Q000378:metabolism
D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D008246:Lysophospholipids; D014280:Triglycerides; D008071:Lipoprotein Lipase