Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration

Taguchi, Tadao; Yamashita, Er.; Mizutani, T.; Nakajima, Hitoshi; Yabuuchi, Masahiko; Asano, Naoki; Miwa, Ichitomo

doi:10.1152/ajpendo.00451.2004

Cited by 30 publications

(36 citation statements)

References 23 publications

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“…Glycogen breakdown has been proposed as a possibility, as shown in rats in response to epinephrine administration (19). Glycogen phosphorylase is activated upon induction of ER stress, which could provide glycosylation precursors during stress (20).…”

Section: Discussionmentioning

confidence: 99%

Mannose Efflux from the Cells

Sharma

Freeze

2011

Journal of Biological Chemistry

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All mammals have 50 -100 M mannose in their blood. However, the source of the dynamic pool of mannose in blood is unknown. Most of it is thought to be derived from glucose in the cells. We studied mannose uptake and release by various cell types. Interestingly, our results show that mannose taken up by the cells through transporters is handled differently from the mannose released within the cells due to glycan processing of protein-bound oligosaccharides. Although more than 95% of incoming mannose is catabolized, most of the mannose released by intracellular processing is expelled from the cells as free mannose predominantly via a nocodazole-sensitive sugar transporter. Under physiological conditions, incoming mannose is more accessible to hexokinase, whereas mannose released within the cells is protected from HK and therefore has a different fate. Our data also suggest that generation of free mannose due to the processing of glycoconjugates composed of glucosederived mannose and its efflux from the cells can account for most of the mannose found in blood and its steady state maintenance.Mannose is an important constituent of N-glycans. The addition of high mannose oligosaccharides to the newly synthesized polypeptide chain and their subsequent processing provide diversity to N-glycan structures. Mannose residues in N-glycans can be derived from either glycogen/glucose or mannose in the blood. Blood has a metabolically active pool of 50 -150 M mannose in steady state; however, mannose homeostasis is not well understood (1). Dietary contribution is insignificant (2), arguing that most of it is probably derived from an endogenous source. Mannose enters the cells via hexose transporters present at the plasma membrane. It is immediately phosphorylated by hexokinase (HK) 2 and then either catabolized via mannose phosphate isomerase (MPI) or diverted toward glycosylation through phosphomannomutase-2 (PMM2) (Scheme 1).Glycosylation precursors, such as mannose 1-phosphate, GDP-mannose, and dolichol phosphate mannose, are used to assemble lipid-linked oligosaccharides (LLO). The glycan portion is then transferred to proteins (3). Mannose, which is incorporated into N-glycans, is trimmed down by mannosidases within the endoplasmic reticulum (ER) and Golgi to generate free mannose. In this study, we show that although more than 95% mannose entering the cell is catabolized, surprisingly, more than 50% of mannose derived from glycan processing and degradation is protected from catabolism and exits the cells as free mannose, most probably via a transporter. This mannose efflux from the cells can account for the majority of mannose found in mammalian blood. EXPERIMENTAL PROCEDURESMaterials-Most of the reagents were purchased from Sigma except BCA protein assay reagent (Pierce). ␣-Minimal essential medium, Dulbecco's modified Eagle's medium (DMEM) with and without glucose, DMEM/F-12 (1:1) medium, and equine serum were from Invitrogen. Fetal bovine serum was obtained from Hyclone Laboratories (Logan, UT). Concanavalin A-Sepharo...

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Section: Discussionmentioning

confidence: 99%

Mannose Efflux from the Cells

Sharma

Freeze

2011

Journal of Biological Chemistry

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“…Little is known about the physiological role of mannose, other than its use in protein glycosylation. Mannose enters the cell via a specific transporter that is insensitive to glucose (Panneerselvam & Freeze 1996), and hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentrations (Taguchi et al 2005). These observations and the association with GCKR detected in the GWAS study, which is even stronger than that of glucose with GCKR, call for further investigation of the role of mannose as a differential biomarker, or even as a potential point of intervention in diabetes care.…”

Section: The Role Of Genetic Variance and The Intermediate Metabolic mentioning

confidence: 95%

Metabolic profiling in diabetes

Suhre¹

2014

Journal of Endocrinology

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Metabolic profiling, or metabolomics, has developed into a mature science in recent years. It has major applications in the study of metabolic disorders. This review addresses issues relevant to the choice of the metabolomics platform, study design and data analysis in diabetes research, and presents recent advances using metabolomics in the identification of markers for altered metabolic pathways, biomarker discovery, challenge studies, metabolic markers of drug efficacy and off-target effects. The role of genetic variance and intermediate metabolic phenotypes and its relevance to diabetes research is also addressed.

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“…The synthesis and degradation of glycogen in the liver are important mechanisms in the control of blood glucose homeostasis [1,2] . The inhibition of enzymes involved in glycogenolysis constitutes an alternative approach to suppressing hepatic glucose production and lowering blood glucose levels [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

Effect of geniposide, a hypoglycemic glucoside, on hepatic regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin

et al. 2009

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Aim: Hepatic glycogen phosphorylase (GP) and glucose-6-phosphatase (G6Pase) play an important role in the control of blood glucose homeostasis and are proposed to be potential targets for anti-diabetic drugs. Geniposide is an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits and has been reported to have a hypoglycemic effect. However, little is known about the biochemical mechanisms by which geniposide regulates hepatic glucose-metabolizing enzymes. The present study investigates whether the hypoglycemic effect of geniposide is mediated by GP or G6Pase. Methods: Type 2 diabetic mice, induced by a high-fat diet and streptozotocin injection, were treated with or without geniposide for 2 weeks. Blood glucose levels were monitored by a glucometer. Insulin concentrations were analyzed by the ELISA method. Total cholesterol (TC) and triglyceride (TG) levels were measured using Labassay TM kits. Activities of hepatic GP and G6Pase were measured by glucose-6-phosphate dehydrogenase-coupled reaction. Real-time RT-PCR and Western blotting were used to determine the mRNA and protein levels of both enzymes. Results: Geniposide (200 and 400 mg/kg) significantly decreased the blood glucose, insulin and TG levels in diabetic mice in a dose-dependent manner. This compound also decreased the expression of GP and G6Pase at mRNA and immunoreactive protein levels, as well as enzyme activity. Conclusion: Geniposide is an effective hypoglycemic agent in diabetic mice. The hypoglycemic effect of this compound may be mediated, at least in part, by inhibiting the GP and G6Pase activities.

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Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration

Cited by 30 publications

References 23 publications

Mannose Efflux from the Cells

Mannose Efflux from the Cells

Metabolic profiling in diabetes

Effect of geniposide, a hypoglycemic glucoside, on hepatic regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin

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