Michael P. Mark

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A new chemical class of potent DPP-4 inhibitors structurally derived from the xanthine scaffold for the treatment of type 2 diabetes has been discovered and evaluated. Systematic structural variations have led to 1 (BI 1356), a highly potent, selective, long-acting, and orally active DPP-4 inhibitor that shows considerable blood glucose lowering in(More)
BI 1356 [proposed trade name ONDERO; (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione] is a novel dipeptidyl peptidase (DPP)-4 inhibitor under clinical development for the treatment of type 2 diabetes. In this study, we investigated the potency, selectivity, mechanism, and duration of(More)
Sodium glucose cotransporters (SGLT) actively catalyse carbohydrate transport across cellular membranes. Six of the 12 known SGLT family members have the capacity to bind and/or transport monosaccharides (SGLT-1 to 6); of these, all but SGLT-5 have been characterised. Here we demonstrate that human SGLT-5 is exclusively expressed in the kidney. Four splice(More)
Within the cholesterol biosynthesis cascade, the enzyme 2,3-oxidosqualene cyclase [EC] is of special interest due to its dual function: cyclization of 2,3-monoepoxysqualene to lanosterol and 2,3;22,23-diepoxysqualene to oxylanosterol. Further determination of the significance of this enzyme for the intracellular cholesterol homeostasis was done(More)
BACKGROUND Dipeptidylpeptidase-4 inhibition is reported to have beneficial effects on myocardial ischemia. Mechanisms might include a reduced degradation of stromal cell-derived factor-1 alpha with subsequent increased recruitment of circulating stem cells and/or incretin receptor-dependent pathways. This study evaluated the novel xanthine-based(More)
Linagliptin (TRADJENTA™) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibition attenuates insulin resistance and improves peripheral glucose utilization in humans. However, the effects of chronic DPP-4 inhibition on insulin sensitivity are not known. The effects of long-term treatment (3-4 weeks) with 3 mg/kg/day or 30 mg/kg/day(More)
Antidiabetic effects of dipeptidyl peptidase-4 (DPP-4) inhibitors are exerted by potentiation of the biological activity of incretin hormones like glucagon-like peptide (GLP)-1. BI 1356 [proposed trade name Ondero; (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione] is a novel competitive,(More)
Although human plasma cholesteryl-ester-transfer protein (CETP) is primarily synthesized in the liver, its expression in a number of transformed liver cell lines is very low. However the use of the human hepatoma cell line HepG2 as a model system for the regulation of CETP on mRNA level is facilitated by a quantitative reverse-transcribed polymerase chain(More)
In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly(More)
Non-alcoholic fatty liver disease (NAFLD) is an umbrella term for a series of hepatic pathologies that begin with relatively benign steatosis and can, with appropriate triggers, lead to the serious entity of non-alcoholic steatohepatitis (NASH). This sets the stage for liver fibrosis and finally the development of cirrhosis in up to 20% of patients with(More)