Our data demonstrate that although DEX and MET are used as anti-inflammatory agents or insulin sensitizers, respectively, their common property to phosphorylate AMPK promotes cardiomyocyte cell survival through its regulation of Bad and the mitochondrial apoptotic mechanism.

Telmisartan is a safe and effective alternative for the treatment of hypertension. Moreover, due to its good tolerability, an increasing use of telmisartan in cardiovascular high risk patients can be anticipated. This will grant further experimental and clinical research on AT1 receptor-independent pharmacodynamics of telmisartan as well as on telmisartan-related drug safety issues.

Following diabetes, the heart increases its lipoprotein lipase (LPL) at the coronary lumen by transferring LPL from the cardiomyocyte to the endothelial lumen. We examined how hyperglycemia controls secretion of heparanase, the enzyme that cleaves myocyte heparan sulphate proteoglycan to initiate this movement. Diazoxide (DZ) was used to decrease serum insulin and generate hyperglycemia. A modified Langendorff technique was used to separate coronary from interstitial effluent, which were assayed for heparanase and LPL. Within 30 min of DZ, interstitial heparanase increased, an effect that closely mirrored an augmentation in interstitial LPL. Endothelial cells were incubated with palmitic acid (PA) or glucose, and heparanase secretion was determined. PA increased intracellular heparanase, with no effect on secretion of this enzyme. Unlike PA, glucose dosedependently lowered endothelial intracellular heparanase, which was strongly associated with increased heparanase activity in the incubation medium. Preincubation with cytochalasin D or nocodazole prevented the high glucose-induced depletion of intracellular heparanase. Our data suggest that following hyperglycemia, translocation of LPL from the cardiomyocyte cell surface to the apical side of endothelial cells is dependent on the ability of the fatty acid to increase endothelial intracellular heparanase followed by rapid secretion of this enzyme by glucose, which requires an intact microtubule and actin cytoskeleton. diabetes; diazoxide; high glucose; endothelial cell; cytoskeleton SINCE UNINTERRUPTED contraction is a unique feature of the heart, cardiac muscle has a high demand for provision of energy (2). Under normal physiological conditions, hearts can utilize multiple substrates, including fatty acid (FA), carbohydrate, amino acid, and ketone bodies. Among these substrates, carbohydrate (ϳ30%) and FA (ϳ70%) are the major sources from which the heart derives most of its energy (29). FA delivery and utilization by the heart involves 1) release from adipose tissue and transport to the heart after complexing with albumin (19), 2) provision through the breakdown of endogenous cardiac triglyceride (TG) stores (23), 3) internalization of whole lipoproteins (14), and 4) hydrolysis of circulating TG-rich lipoproteins (very low density lipoproteins and chylomicrons) to FA by lipoprotein lipase (LPL) positioned at the endothelial surface of the coronary lumen (4). Despite this critical function, coronary endothelial cells do not synthesize LPL (6). In the heart, this enzyme is produced in cardiomyocytes and subsequently secreted onto heparan sulphate proteoglycan (HSPG) binding sites on the myocyte cell surface (11). From here, LPL is transported onto comparable binding sites on the luminal surface of endothelial cells (3). At the lumen, LPL actively metabolizes the TG core of lipoproteins to FA; these released FA are then transported into the heart for numerous metabolic and structural functions.LPL synthesis and activity is regulated in a tissue-specific manner by v...

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