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Metalloprotease inhibitors regulate biliary progenitor cells through sDLK1 in organoid models of liver injury.
J Clin Invest
December 2024
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Understanding cell fate regulation in the liver is necessary to advance cell therapies for hepatic disease. Liver progenitor cells (LPC) contribute to tissue regeneration after severe hepatic injury yet signals instructing progenitor cell dynamics and fate are largely unknown. The Tissue Inhibitor of Metalloproteinases, TIMP1 and TIMP3 control the sheddases ADAM10 and ADAM17, key for NOTCH activation.
View Article and Find Full Text PDFRisk of Atherosclerosis Due to HMGB1-dependent Platelet-derived Microparticles in Patients with Type 2 Diabetes Mellitus.
Clin Appl Thromb Hemost
November 2024
First Department of Internal Medicine, Kansai Medical University, Hirakata, Japan.
We measured high mobility group box 1 protein (HMGB1) and platelet-derived microparticles (PDMP) in blood samples from patients with untreated type 2 diabetes mellitus (T2DM). We examined the effects of a combination of sodium/glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Multiple regression analysis of HMGB1 was conducted on data from 252 patients in our previously reported T2DM-related clinical study.
View Article and Find Full Text PDFElucidation of DPP-4 involvement in systemic distribution and renal reabsorption of linagliptin by PBPK modeling with a cluster Gauss-Newton method.
Clin Transl Sci
October 2024
Laboratory of Clinical Pharmacology, Yokohama University of Pharmacy, Yokohama-shi, Kanagawa, Japan.
The dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (LNG) exhibits target-mediated drug disposition (TMDD) in clinical settings, characterized by saturable binding to plasma soluble DPP-4 (sDPP-4) and tissue transmembrane DPP-4 (tDPP-4). Previous studies have indicated that saturable renal reabsorption of LNG contributes to its nonlinear urinary excretion observed in humans and wild-type mice, but not in Dpp-4 knockout mice. To elucidate the mechanisms underlying these complex phenomena, including DPP-4-related renal reabsorption of LNG, we employed physiologically-based pharmacokinetic (PBPK) modeling combined with a cluster Gauss-Newton method (CGNM).
View Article and Find Full Text PDFAntidiabetic Agents and Bone Quality: A Focus on Glycation End Products and Incretin Pathway Modulations.
J Bone Metab
August 2024
Department of Pharmacology and Toxicology, College of Pharmacy, University of Mosul, Mosul, Iraq.
Diabetes mellitus is associated with inadequate bone health and quality and heightened susceptibility to fractures, even in patients with normal or elevated bone mineral density. Elevated advanced glycation end-products (AGEs) and a suppressed incretin pathway are among the mechanisms through which diabetes affects the bone. Accordingly, the present review aimed to investigate the effects of antidiabetic medications on bone quality, primarily through AGEs and the incretin pathway.
View Article and Find Full Text PDFTherapeutic Potential of Luteolin for Diabetes Mellitus and Its Complications.
Chin J Integr Med
September 2024
Endocrinology Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
The global prevalence of diabetes mellitus (DM) and its complications has been showing an upward trend in the past few decades, posing an increased economic burden to society and a serious threat to human life and health. Therefore, it is urgent to investigate the effectiveness of complementary and alternative therapies for DM and its complications. Luteolin is a kind of polyphenol flavonoid with widely existence in some natural resources, as a safe dietary supplement, it has been widely studied and reported in the treatment of DM and its complications.
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