Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increased cardiovascular risk is accompanied with diabetes-induced endothelial dysfunction. Pharmacological agents with endothelium-protective effects may decrease cardiovascular complications. In present study sulodexide (glycosaminoglycans composed from heparin-like and dermatan fractions) was chosen to evaluate its protective properties on endothelial dysfunction in diabetes. Effect of sulodexide treatment (SLX, 100 UI/kg/day, i.p.) in 5 and 10 weeks lasting streptozotocin-induced diabetes (30 mg/kg/day, i.p. administered for three consecutive days) was investigated. Animals were divided into four groups: control (injected with saline solution), control-treated with sulodexide (SLX), diabetic (DM) and diabetic-treated with sulodexide (DM+SLX). The pre-prandial and postprandial plasma glucose levels, number of circulating endothelial cells (EC) and acetylcholine-induced relaxation of isolated aorta and mesenteric artery were evaluated. Streptozotocin elicited hyperglycemia irrespective of SLX treatment. Streptozotocin-induced diabetes enhanced the number of circulating endothelial cells compared to controls. SLX treatment decreased the number of EC in 10-week diabetes. Acetylcholine-induced relaxation of mesenteric arteries was significantly impaired in 5 and 10-week diabetes. SLX administration improved relaxation to acetylcholine in 5 and 10-week diabetes. Diabetes impaired acetylcholine-induced relaxation of rat aorta irrespective of SLX treatment. Our results demonstrate that SLX treatment lowers the number of circulating endothelial cells and improves endothelium-dependent relaxation in small arteries. These findings suggest endothelium-protective effect of sulodexide in streptozotocin-induced diabetes.
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http://dx.doi.org/10.33549/physiolres.931506 | DOI Listing |
Mol Ther
January 2025
Department of Molecular Medicine, University of Southern Denmark; Odense, 5230, Denmark. Electronic address:
Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
January 2025
Department of Biomedical Sciences, Grand Valley State University, Allendale, MI 49401, USA.
Background: Diabetes mellitus is associated with morphological and functional impairment of the heart primarily due to lipid toxicity caused by increased fatty acid metabolism. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) have been implicated in the metabolism of fatty acids in the liver and skeletal muscles. However, their role in the heart in diabetes remains unclear.
View Article and Find Full Text PDFNutrients
January 2025
Department of Pharmacy and Master Program, Collage of Pharmacy and Health Care, Tajen University, Yanpu Township 90741, Taiwan.
: This study investigated the wound-healing potential of hispolon, a polyphenolic pigment derived from medicinal mushrooms, under diabetic conditions using both in vitro and in vivo models. : In the in vitro assays, L929 fibroblast cells exposed to high glucose (33 mmol/L) were treated with hispolon at concentrations of 2.5, 5, 7.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg 194223, Russia.
The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)--1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM).
View Article and Find Full Text PDFAntioxidants (Basel)
December 2024
Research Institute for Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea.
Diabetic foot ulcers represent a severe complication of diabetes, often resulting in amputation and high mortality rates. Currently, there are no treatments for diabetic foot ulcers other than antibiotics and dressings. In this study, we evaluated the wound-healing effects of an antidiabetic agent pinitol in lipopolysaccharide (LPS)-damaged human dermal fibroblasts (HDFs) and streptozotocin (STZ)-induced diabetic rat models with a foot wound.
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