Lipoprotein lipase activity is stimulated by insulin and dexamethasone in cardiomyocytes from diabetic rats

Type 1 diabetes mellitus reduces lipoprotein lipase (LPL) activity in the h eart. The diabetic phenotype of decreased LPL activity in freshly isolated cardiomyocytes persisted after overnight culture (16 h). Total cellular LPL activity was 311 +/- 56 nmol oleate released.h(-1)mg(-1) cell protein in d iabetic cultured cardiomyocytes compared with 661 +/- 81 nmol oleate releas ed.h(-1).mg(-1) cell protein for control cultured cells. Diabetes also resu lted in lower heparin-releasable (HR) LPL activity compared with control ce lls (111 +/- 25 vs. 432 +/- 63 nmol.h(-1).mg(-1) cell protein). In kinetic experiments, the reduction in total cellular LPL and HR-LPL activities in c ultured cells from diabetic hearts was due to a decrease in maximal velocit y, with no change in apparent K-m, for substrate (triolein). LPL activity i n primary cultures of cardiomyocytes from control rats is stimulated by the combination of insulin (Ins) and dexamethasone (Dex). Overnight treatment of cultured cardiomyocytes from diabetic rats with Ins+Dex elicited an 84% increase in cellular LPL activity (to 572 +/- 65 nmol.h(-1).mg(-1) cell pro tein) and a 194% increase in HR-LPL activity (to 326 +/- 46 nmol.h(-1).mg(- 1) cell protein). This stimulation occurred at subnanomolar concentrations of the hormones, but neither hormone was effective alone. The amount of imm unoreactive LPL protein mass in cultured cardiomyocytes from diabetic heart s was unchanged by Ins+Dex treatment. Addition of oleic acid (60 mu M) to t he overnight culture medium inhibited the already reduced HR-LPL activity i n diabetic cultured cells by 73% (to 30 +/- 4 nmol.h(-1).mg(-1) cell protei n). The presence of oleic acid also reduced hormone-stimulated HR-LPL activ ity. Increasing the glucose concentration in the culture medium to 26 mM ha d no effect on total cellular LPL or HR-LPL activities.