The first paper of this subject is paywalled:
However, eventual papers seems to indicate its effect is mTOR-dependent, through the downregulation of mTOR signalling pathway.Biochem Biophys Res Commun. 2010 Jan 22;391(4):1775-9.
Glucosamine induces autophagy via an mTOR-independent pathway
Tomoya Shintani , Fumiyoshi Yamazaki, Toshihiko Katoh, Midori Umekawa, Yoshiharu Matahira, Seiji Hori, Akira Kakizuka, Kazuhide Totani, Kenji Yamamoto, Hisashi Ashida
PMID: 20045674 DOI: 10.1016/j.bbrc.2009.12.154
Abstract
Autophagy is a cellular process that nonspecifically degrades cytosolic components and is involved in many cellular responses. We found that amino sugars with a free amino group such as glucosamine, galactosamine and mannosamine induced autophagy via an mTOR-independent pathway. Glucosamine-induced autophagy at concentrations of at least 500 microM to over 40 mM. In the presence of 40 mM glucosamine, autophagy induction was initiated at 6h and reached a plateau at 36 h. Glucosamine-induced autophagy could remove accumulated ubiquitin-conjugated proteins as well as 79-glutamine repeats. Therefore, orally administered glucosamine could contribute to the prevention of neurodegenerative diseases and promotion of antiaging effects.
Arthritis Rheum. 2013 Jul;65(7):1843-52.
Glucosamine activates autophagy in vitro and in vivo
Beatriz Caramés , William B Kiosses, Yukio Akasaki, Diana C Brinson, William Eap, James Koziol, Martin K Lotz
PMID: 23606170 PMCID: PMC3772083 DOI: 10.1002/art.37977
Free PMC article
Abstract
[...]
Methods: Chondrocytes from normal human articular cartilage were treated with glucosamine (0.1- 10 mM). Autophagy activation and phosphorylation levels of Akt, FoxO3, and ribosomal protein S6 were determined by Western blotting. Autophagosome formation was analyzed by confocal microscopy. Reporter mice systemically expressing green fluorescent protein (GFP) fused to light chain 3 (LC3) (GFP-LC3-transgenic mice) were used to assess changes in autophagy in response to starvation and glucosamine treatment.
Results: Glucosamine treatment of chondrocytes activated autophagy, as indicated by increased LC3-II levels, formation of LC3 puncta, and increased LC3 turnover. This was associated with glucosamine-mediated inhibition of the Akt/FoxO3/mammalian target of rapamycin pathway. Administration of glucosamine to GFP-LC3-transgenic mice markedly activated autophagy in articular cartilage.
Conclusion: Glucosamine modulates molecular targets of the autophagy pathway in vitro and in vivo, and the enhancement of autophagy is mainly dependent on the Akt/FoxO/mTOR pathway. These findings suggest that glucosamine is an effective autophagy activator and should motivate future studies on the efficacy of glucosamine in modifying aging-related cellular changes and supporting joint health.
J Orthop Res. 2014 Nov;32(11):1532-42.
Glucosamine protects nucleus pulposus cells and induces autophagy via the mTOR-dependent pathway
LiBo Jiang , YongLong Jin, HuiRen Wang, YunQi Jiang, Jian Dong
PMID: 25087910 DOI: 10.1002/jor.22699
Free article
Abstract
Although glucosamine has been suggested to be effective in the treatment of osteoarthritis, its effect on disc degeneration remains unclear. We sought to explore whether glucosamine can activate autophagy in rat nucleus pulposus (NP) cells and protect cells treated with IL-1β or hydrogen peroxide (H2O2). Autophagy in cells was examined by detecting for LC3, Beclin-1, m-TOR, and p70S6K, as well as by analyzing autophagosomes. To inhibit autophagy, 3-methyladenine (3-MA) was used. In the cells treated with IL-1β, the levels of Adamts-4, Mmp-13, aggrecan, and Col2a1 were analyzed by real-time PCR and immunofluorescence. Apoptosis was analyzed by TUNEL. Cell senescence under H2O2 was revealed by SA-β-Gal staining. Glucosamine could activate autophagy in a dose-dependent manner within 24 h and inhibit the phosphorylation of m-TOR and p70S6K. Autophagy in IL-1β or H2O2 -treated cells was increased by glucosamine. Glucosamine attenuated the decrease of aggrecan and prevented the apoptosis of the NP cells induced by IL-1β, whereas 3-MA partly reversed these effects. The percentage of SA-β-Gal-positive cells induced by H2O2 treatment was decreased by glucosamine, accompanied by the decline of p70S6K phosphorylation. Glucosamine protects NP cells and up-regulates autophagy by inhibiting the m-TOR pathway, which might point a potential therapeutic agent for disc degeneration.
Int J Mol Sci. 2018 May 9;19(5):1416.
Glucosamine-Induced Autophagy through AMPK⁻mTOR Pathway Attenuates Lipofuscin-Like Autofluorescence in Human Retinal Pigment Epithelial Cells In Vitro
Ching-Long Chen , Yi-Hao Chen, Chang-Min Liang, Ming-Cheng Tai, Da-Wen Lu, Jiann-Torng Chen
PMID: 29747425 PMCID: PMC5983587 DOI: 10.3390/ijms19051416
Free PMC article
Abstract
Age-related macular degeneration (AMD) is a vision-threatening age-associated disease. The retinal pigment epithelial (RPE) cells phagocytose and digest photoreceptor outer segment (POS). Incomplete digestion of POS leads to lipofuscin accumulation, which contributes to the pathology of the AMD. Autophagy could help reduce the amount of lipofuscin accumulation. In the present study, we evaluated the effects of glucosamine (GlcN), a natural supplement, on the induction of autophagy and POS-derived lipofuscin-like autofluorescence (LLAF) in ARPE-19 cells in vitro, and investigated the potential molecular pathway involved. Our results revealed that GlcN had no effect on phagocytosis of POS at the lower doses. GlcN treatment induced autophagy in cells. GlcN decreased the LLAF in native POS-treated cells, whereas malondialdehyde or 4-hydroxynonenal-modified POS attenuated this effect. 3-Methyladenine inhibited GlcN-induced autophagy and attenuated the effect of GlcN on the decrease of the native POS-derived LLAF. Furthermore, GlcN induced the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR), whereas Compound C inhibited these effects of GlcN. Altogether, these results suggest that GlcN decreased the native POS-derived LLAF through induction of autophagy, at least in part, by the AMPK⁻mTOR pathway. This mechanism has potential for the preventive treatment of lipofuscin-related retinal degeneration such as AMD.
And the most recent one is quite confusing, by saying glucosamine "inducing autophagic stress through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling"...Biomed Pharmacother. 2018 Mar;99:271-277.
Glucosamine promotes osteoblast proliferation by modulating autophagy via the mammalian target of rapamycin pathway
Chen Lv , Lu Wang 1, Xiongbai Zhu 1, Wenjun Lin 1, Xin Chen 1, Zhengxiang Huang 1, Lintuo Huang 1, Shengwu Yang 2
PMID: 29334671 DOI: 10.1016/j.biopha.2018.01.066
Abstract
Glucosamine is effective in the treatment of osteoarthritis; however, its effect on osteoporosis remains unclear. Decreased activity of osteoblasts is the main cause of osteoporosis. Here, we examined the effects of glucosamine on osteoblasts. The potential underlying mechanisms were explored. The results showed that glucosamine had a biphasic effect on the viability of hFOB1.19 osteoblasts. At low concentrations (<0.6 mM), glucosamine induced hFOB1.19 cell proliferation, whereas at high concentrations (>0.8 mM) it induced apoptosis. The autophagy inhibitor 3-methyladenine (3-MA) was used to verify that glucosamine modulated hFOB1.19 cell viability via autophagy. The induction of apoptosis by high concentrations of glucosamine was significantly exacerbated by 3-MA, whereas the promotion of cell proliferation by low concentrations of glucosamine was significantly suppressed by 3-MA. Autophagy was examined by western blot detection of autophagy-related proteins including LC3, Beclin-1, and SQSTM1/p62 and by immunofluorescence analysis of autophagosomes. Glucosamine activated autophagy in a time- and concentration-dependent manner. Investigation of the underlying mechanism showed that glucosamine inhibited the phosphorylation of m-TOR in a concentration-dependent manner within 48 h, and rapamycin significantly inhibited the phosphorylation of m-TOR. These results demonstrated that glucosamine promoted hFOB1.19 cell proliferation and increased autophagy by inhibiting the m-TOR pathway, suggesting its potential as a therapeutic agent for osteoporosis.
What do you think?Autophagy. 2020 Mar;16(3):548-561.
Glucosamine promotes hepatitis B virus replication through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling
Yong Lin, Chunchen Wu , Xueyu Wang , Shi Liu, Kaitao Zhao, Thekla Kemper , Haisheng Yu, Mengqi Li, Jiming Zhang, Mingzhou Chen, Ying Zhu, Xinwen Chen, Mengji Lu
PMID: 31204557 PMCID: PMC6999643 DOI: 10.1080/15548627.2019.1632104
Free PMC article
Abstract
Glucosamine (GlcN), a dietary supplement widely utilized to promote joint health and effective in the treatment of osteoarthritis, is an effective macroautophagy/autophagy activator in vitro and in vivo. Previous studies have shown that autophagy is required for hepatitis B virus (HBV) replication and envelopment. The objective of this study was to determine whether and how GlcN affects HBV replication, using in vitro and in vivo experiments. Our data demonstrated that HBsAg production and HBV replication were significantly increased by GlcN treatment. Confocal microscopy and western blot analysis showed that the amount of autophagosomes and the levels of autophagic markers MAP1LC3/LC3-II and SQSTM1 were clearly elevated by GlcN treatment. GlcN strongly blocked autophagic degradation of HBV virions and proteins by inhibiting lysosomal acidification through its amino group. Moreover, GlcN further promoted HBV replication by inducing autophagosome formation via feedback inhibition of mechanistic target of rapamycin kinase complex 1 (MTORC1) signaling in an RRAGA (Ras related GTP binding A) GTPase-dependent manner. In vivo, GlcN application promoted HBV replication and blocked autophagic degradation in an HBV hydrodynamic injection mouse model. In addition, GlcN promoted influenza A virus, enterovirus 71, and vesicular stomatitis virus replication in vitro. In conclusion, GlcN efficiently promotes virus replication by inducing autophagic stress through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling. Thus, there is a potential risk of enhanced viral replication by oral GlcN intake in chronically virally infected patients.
