Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine

Abstract

The hexose transporter, GLUT2 (SLC2A2), which is expressed by mouse embryos, is important for survival before embryonic day 10.5, but its function in embryos is unknown. GLUT2 can transport the amino sugar glucosamine (GlcN), which could increase substrate for the hexosamine biosynthetic pathway (HBSP) that produces UDP-N-acetylglucosamine for O-linked N-acetylglucosamine modification (O-GlcNAcylation) of proteins. To understand this, we employed a novel murine embryonic stem cell (ESC) line that, like mouse embryos, expresses functional GLUT2 transporters. GlcN stimulated ESC proliferation in a GLUT2-dependent fashion but did not regulate pluripotency. Stimulation of proliferation was not due to increased O-GlcNAcylation. Instead, GlcN decreased dependence of the HBSP on fructose-6-PO4 and glutamine. Consequently, glycolytic- and glutamine-derived intermediates that are needed for anabolic metabolism were increased. Thus, maternally obtained GlcN may increase substrates for biomass accumulation by embryos, as exogenous GlcN does for GLUT2-expressing ESC, and may explain the need for GLUT2 expression by embryos.

Glucose metabolism regulates expression of hair-inductive genes of dermal papilla spheres via histone acetylation

“…2). Carbohydrates including galactose, glucosamine and fructose are transported through glucose transporters and utilized in glucose metabolism 14,15 . Therefore, excessive carbohydrates-mediated DP inductivity should be determined in the future.…”

Direct conversion from skin fibroblasts to functional dopaminergic neurons for biomedical application

“…Acetyl-CoA, methionine, and α-ketoglutarate are the key metabolites that are either a source or cofactor of acetylation, methylation, and dimethylation. Moreover, metabolites like glucosamine-induced stem cell proliferation and differentiation by regulating both epigenetic control and anabolic metabolism (Hwang et al 2016;TeSlaa et al 2016;Carey et al 2015;Jung et al 2016;Jang et al 2012). Thus, metabolic reprogramming is one of the candidates to further examine for regulation of cell fate plasticity.…”

Multifaceted Protective Role of Glucosamine against Osteoarthritis: Review of Its Molecular Mechanisms

“…Glucosamine treatment remarkably increased the size of ESC organoids with the accumulation of GAG; downregulation of type X collagen gene expression; and upregulation of aggrecan, type II collagen, and transcription factor Sox-9 gene expression [125]. Mechanistically, glucosamine stimulates ESC proliferation via the glucose transporter-2-dependent increase for glycolytic-and glutamine-derived intermediates, which could reduce the dependence on the hexosamine biosynthetic pathway [121].…”

“…Glucosamine and its derivatives inhibit osteoclastic differentiation [120] and enhance stem cells proliferation [121][122][123][124], chondrogenic differentiation or chondrogenesis [106,[122][123][124][125][126][127] and osteoblastic differentiation [120]. Glucosamine (0.1 and 1 mM) and N-acetyl glucosamine induced differentiation of mouse MC3T3-E1 osteoblasts by increasing the mineralisation of extracellular matrix and the expression of osteopontin (middle-stage osteoblastic differentiation biomarker) and osteocalcin (late-stage osteoblastic differentiation biomarker) [120].…”

“…High doses ↓cartilage degradation↓ peroxisomal oxidation [104] Human articular cartilage chondrocytes were treated with glucosamine (0.1-10 mM) for 8 and 24 h ↑ LC3-II/LC3-I ratio ↑ autophagy flux Inhibited Akt/FoxO3/mTOR phosphorylation GFP-LC3-transgenic mice were treated with glucosamine (250 mg/kg body weight/day) via oral and intraperitoneal administration for 7 days ↑ autophagy in the mice liver and knee joint cartilage [105] Human hFOB1.19 osteoblasts were treated with glucosamine (0.2-1 mM) up to 48 h ↑ LC3 II and Beclin 1 ↓ SQSTM1/p62 Inhibited mTOR phosphorylation [83] Normal human articular chondrocytes were treated with glucosamine sulfate (10 mM) and then stimulated with IL-1β (10 ng/mL) ↑ GRP78, HSP7C and PDIA1/3 protein levels Tissue regeneration (stem cell proliferation and differentiation) [121] Low glucose-isolated ESCs that highly expressed glucose transporter 2 were treated with glucosamine (0.8 and 2 mM) for 4 days ↑ ESCs proliferation [106] hMSCs were treated with glucosamine hydrochloride (100 µM and 1 mM) for 11 days ↑ chondrogenesis (↑ type II collagen, aggrecan, and sulfated GAG levels) [106] Primary normal and OA chondrocytes were treated with glucosamine hydrochloride (100 µM and 1 mM) for 11 days ↑ chondrogenic phenotypes with the restoration of type II collagen, aggrecan, and sulfated GAG levels Partially blocked IL-1β-mediated downregulation of type II collagen and aggrecan genes expression and inhibited the MMP-13 gene expression [125] 3D-culture of murine ESCs were treated with 2 mM glucosamine, together with glycoproteins, hyaluronic acid, chondroitin sulfate, and heparin sulfate for 21 days ↑ ESC organoids size ↑ chondrogenesis (↑ GAG, aggrecan, type II collagen and Sox-9 genes expression and ↓ type X collagen) [128] Chondrogenic ATDC5 cells were treated with 4.6 mM glucosamine for 5 and 35 days ↓ calcium deposition and mineralization with ↑ sulfated GAG level and ↓ SMAD2/4 and MGP genes expression [120] MC3T3-E1 osteoblasts were treated with glucosamine (0.1 mM and 1 mM) and N-acetyl glucosamine for 3 and 21 days ↑ osteoblastic differentiation (↑ osteopontin and osteocalcin levels) ↓ osteoclastic differentiation (↓ RANKL level) [126] Male New Zealand white rabbits with surgical-induced knee joint cartilage damage were received ACI surgical repair treatment with or without the oral gavage of glucosamine sulphate (…”