Localization of Lipoprotein Lipase in the Diabetic Heart: Regulation by Acute Changes in Insulin

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 19; no. 6; pp. 1526 - 1534
• Main Authors: Sambandam, Nandakumar, Abrahani, Mohammed A, St. Pierre, Edith, Al-Atar, Osama, Cam, Margaret C, Rodrigues, Brian
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-06-1999; Hagerstown, MD Lippincott
• Subjects: Animals; Associated diseases and complications; Biological and medical sciences; Diabetes Mellitus, Experimental - enzymology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Fasting; Fatty Acids, Nonesterified - metabolism; Immunohistochemistry; Insulin - blood; Lipoprotein Lipase - analysis; Male; Medical sciences; Myocardium - enzymology; Perfusion; Rats; Rats, Wistar; Streptozocin; Endocrinopathy; Heart; Rat; Enzyme; Cardiomyopathy; Immunocytochemistry; Pathogenesis; Diabetes mellitus; Rodentia; Cardiovascular disease; Esterases; Lipoprotein lipase; Myocardial disease; Insulin; Carboxylic ester hydrolases; Pathology; Vertebrata; Mammalia; Heart disease; Animal; Hydrolases; Complication
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.19.6.1526

Vascular endothelium-bound lipoprotein lipase (LPL) is rate limiting for free fatty acid (FFA) transport into tissues. In streptozotocin (STZ)-diabetic rats, we have previously demonstrated an increased heparin-releasable LPL activity from perfused hearts. Because heparin can traverse the endothelial barrier, conventional Langendorff retrograde perfusion of the heart with heparin could release LPL from both the capillary luminal and abluminal surfaces. To determine the precise location of the augmented LPL, a modified Langendorff retrograde perfusion was used to isolate the enzyme at the coronary lumen from that in the interstitial effluent. In response to heparin, a 4-fold increase in LPL activity and protein mass was observed in the coronary perfusate after 2 weeks of STZ diabetes. Release of LPL activity into the interstitial fluid of control hearts was slow but progressive, whereas in diabetic hearts, peak enzyme activity was observed within 1 to 2 minutes after heparin, followed by a gradual decline. Immunohistochemical studies of myocardial sections confirmed that the augmented LPL in diabetic hearts was mainly localized at the capillary endothelium. To study the acute effects of insulin on endothelial LPL activity, we examined rat hearts at various times after the onset of hyperglycemia. An increased heparin-releasable LPL activity in diabetic rats was demonstrated shortly (6 to 24 hours) after STZ injection or after withdrawal from exogenous insulin. Heparin-releasable coronary LPL activity was also increased after an overnight fast. These studies indicate that the intravascular heparin-releasable fraction of cardiac LPL activity is acutely regulated by short-term changes in insulin rather than glucose. Thus, during short periods (hours) of hypoinsulinemia, increased LPL activity at the capillary endothelium can increase the delivery of FFAs to the heart. The resultant metabolic changes could induce the subsequent cardiomyopathy that is observed in the chronic diabetic rat. (Arterioscler Thromb Vasc Biol. 1999;19:1526-1534.)