Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis

Research output: Contribution to journal › Journal article › Research › peer-review

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Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis. / Von Wilamowitz-Moellendorff, Alexander; Hunter, Roger W.; García-Rocha, Mar; Kang, Li; López-Soldado, Iliana; Lantier, Louise; Patel, Kashyap; Peggie, Mark W.; Martínez-Pons, Carlos; Voss, Martin; Calbó, Joaquim; Cohen, Patricia T.W.; Wasserman, David H.; Guinovart, Joan J.; Sakamoto, Kei.

In: Diabetes, Vol. 62, No. 12, 01.12.2013, p. 4070-4082.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Von Wilamowitz-Moellendorff, A, Hunter, RW, García-Rocha, M, Kang, L, López-Soldado, I, Lantier, L, Patel, K, Peggie, MW, Martínez-Pons, C, Voss, M, Calbó, J, Cohen, PTW, Wasserman, DH, Guinovart, JJ & Sakamoto, K 2013, 'Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis', Diabetes, vol. 62, no. 12, pp. 4070-4082. https://doi.org/10.2337/db13-0880

APA

Von Wilamowitz-Moellendorff, A., Hunter, R. W., García-Rocha, M., Kang, L., López-Soldado, I., Lantier, L., Patel, K., Peggie, M. W., Martínez-Pons, C., Voss, M., Calbó, J., Cohen, P. T. W., Wasserman, D. H., Guinovart, J. J., & Sakamoto, K. (2013). Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis. Diabetes, 62(12), 4070-4082. https://doi.org/10.2337/db13-0880

Vancouver

Von Wilamowitz-Moellendorff A, Hunter RW, García-Rocha M, Kang L, López-Soldado I, Lantier L et al. Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis. Diabetes. 2013 Dec 1;62(12):4070-4082. https://doi.org/10.2337/db13-0880

Author

Von Wilamowitz-Moellendorff, Alexander ; Hunter, Roger W. ; García-Rocha, Mar ; Kang, Li ; López-Soldado, Iliana ; Lantier, Louise ; Patel, Kashyap ; Peggie, Mark W. ; Martínez-Pons, Carlos ; Voss, Martin ; Calbó, Joaquim ; Cohen, Patricia T.W. ; Wasserman, David H. ; Guinovart, Joan J. ; Sakamoto, Kei. / Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis. In: Diabetes. 2013 ; Vol. 62, No. 12. pp. 4070-4082.

Bibtex

@article{a96be3e4eb6e4079a798ff3e4d61698f,
title = "Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis",
abstract = "The liver responds to an increase in blood glucose levels in the postprandial state by uptake of glucose and conversion to glycogen. Liver glycogen synthase (GYS2), a key enzyme in glycogen synthesis, is controlled by a complex interplay between the allosteric activator glucose-6-phosphate (G6P) and reversible phosphorylation through glycogen synthase kinase-3 and the glycogen-associated form of protein phosphatase 1. Here, we initially performed mutagenesis analysis and identified a key residue (Arg582) required for activation of GYS2 by G6P. We then used GYS2 Arg582Ala knockin (+/R582A) mice in which G6Pmediated GYS2 activation had been profoundly impaired (60-70%), while sparing regulation through reversible phosphorylation. R582A mutant-expressing hepatocytes showed significantly reduced glycogen synthesis with glucose and insulin or glucokinase activator, which resulted in channeling glucose/G6P toward glycolysis and lipid synthesis. GYS2+/R582A mice were modestly glucose intolerant and displayed significantly reduced glycogen accumulation with feeding or glucose load in vivo. These data show that G6P-mediated activation of GYS2 plays a key role in controlling glycogen synthesis and hepatic glucose-G6P flux control and thus whole-body glucose homeostasis.",
author = "{Von Wilamowitz-Moellendorff}, Alexander and Hunter, {Roger W.} and Mar Garc{\'i}a-Rocha and Li Kang and Iliana L{\'o}pez-Soldado and Louise Lantier and Kashyap Patel and Peggie, {Mark W.} and Carlos Mart{\'i}nez-Pons and Martin Voss and Joaquim Calb{\'o} and Cohen, {Patricia T.W.} and Wasserman, {David H.} and Guinovart, {Joan J.} and Kei Sakamoto",
year = "2013",
month = dec,
day = "1",
doi = "10.2337/db13-0880",
language = "English",
volume = "62",
pages = "4070--4082",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "12",

}

RIS

TY - JOUR

T1 - Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis

AU - Von Wilamowitz-Moellendorff, Alexander

AU - Hunter, Roger W.

AU - García-Rocha, Mar

AU - Kang, Li

AU - López-Soldado, Iliana

AU - Lantier, Louise

AU - Patel, Kashyap

AU - Peggie, Mark W.

AU - Martínez-Pons, Carlos

AU - Voss, Martin

AU - Calbó, Joaquim

AU - Cohen, Patricia T.W.

AU - Wasserman, David H.

AU - Guinovart, Joan J.

AU - Sakamoto, Kei

PY - 2013/12/1

Y1 - 2013/12/1

N2 - The liver responds to an increase in blood glucose levels in the postprandial state by uptake of glucose and conversion to glycogen. Liver glycogen synthase (GYS2), a key enzyme in glycogen synthesis, is controlled by a complex interplay between the allosteric activator glucose-6-phosphate (G6P) and reversible phosphorylation through glycogen synthase kinase-3 and the glycogen-associated form of protein phosphatase 1. Here, we initially performed mutagenesis analysis and identified a key residue (Arg582) required for activation of GYS2 by G6P. We then used GYS2 Arg582Ala knockin (+/R582A) mice in which G6Pmediated GYS2 activation had been profoundly impaired (60-70%), while sparing regulation through reversible phosphorylation. R582A mutant-expressing hepatocytes showed significantly reduced glycogen synthesis with glucose and insulin or glucokinase activator, which resulted in channeling glucose/G6P toward glycolysis and lipid synthesis. GYS2+/R582A mice were modestly glucose intolerant and displayed significantly reduced glycogen accumulation with feeding or glucose load in vivo. These data show that G6P-mediated activation of GYS2 plays a key role in controlling glycogen synthesis and hepatic glucose-G6P flux control and thus whole-body glucose homeostasis.

AB - The liver responds to an increase in blood glucose levels in the postprandial state by uptake of glucose and conversion to glycogen. Liver glycogen synthase (GYS2), a key enzyme in glycogen synthesis, is controlled by a complex interplay between the allosteric activator glucose-6-phosphate (G6P) and reversible phosphorylation through glycogen synthase kinase-3 and the glycogen-associated form of protein phosphatase 1. Here, we initially performed mutagenesis analysis and identified a key residue (Arg582) required for activation of GYS2 by G6P. We then used GYS2 Arg582Ala knockin (+/R582A) mice in which G6Pmediated GYS2 activation had been profoundly impaired (60-70%), while sparing regulation through reversible phosphorylation. R582A mutant-expressing hepatocytes showed significantly reduced glycogen synthesis with glucose and insulin or glucokinase activator, which resulted in channeling glucose/G6P toward glycolysis and lipid synthesis. GYS2+/R582A mice were modestly glucose intolerant and displayed significantly reduced glycogen accumulation with feeding or glucose load in vivo. These data show that G6P-mediated activation of GYS2 plays a key role in controlling glycogen synthesis and hepatic glucose-G6P flux control and thus whole-body glucose homeostasis.

UR - http://www.scopus.com/inward/record.url?scp=84891797370&partnerID=8YFLogxK

U2 - 10.2337/db13-0880

DO - 10.2337/db13-0880

M3 - Journal article

C2 - 23990365

AN - SCOPUS:84891797370

VL - 62

SP - 4070

EP - 4082

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 12

ER -

ID: 239216185