The Importance of Glycogen Molecular Structure for Blood Glucose Control

Overview

Journal iScience

Publisher Cell Press

Date 2021 Jan 18

PMID 33458612

Citations 2

Authors

Asad Nawaz

Peng Zhang

Enpeng Li

Robert G Gilbert

Mitchell A Sullivan

Affiliations

Soon will be listed here.

Abstract

Type 2 diabetes incidence continues to increase rapidly. This disease is characterized by a breakdown in blood glucose homeostasis. The impairment of glycemic control is linked to the structure of glycogen, a highly branched glucose polymer. Liver glycogen, a major controller of blood sugar, comprises small β particles which can link together to form larger α particles. These degrade to glucose more slowly than β particles, enabling a controlled release of blood glucose. The α particles in diabetic mice are however easily broken down into β particles, which degrade more quickly. Because this may lead to higher blood glucose, understanding this diabetes-associated breakdown of α-particle molecular structure may help in the development of diabetes therapeutics. We review the extraction of liver glycogen, its molecular structure, and how this structure is affected by diabetes and then use this knowledge to make postulates to guide the development of strategies to help mitigate type 2 diabetes.

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References

Morell M, Samuel M, OShea M . Analysis of starch structure using fluorophore-assisted carbohydrate electrophoresis. Electrophoresis. 1998; 19(15):2603-11. DOI: 10.1002/elps.1150191507. View

KRISMAN C, Barengo R . A precursor of glycogen biosynthesis: alpha-1,4-glucan-protein. Eur J Biochem. 1975; 52(1):117-23. DOI: 10.1111/j.1432-1033.1975.tb03979.x. View

Parker G, Koay A, Gilbert-Wilson R, Waddington L, Stapleton D . AMP-activated protein kinase does not associate with glycogen alpha-particles from rat liver. Biochem Biophys Res Commun. 2007; 362(4):811-5. DOI: 10.1016/j.bbrc.2007.08.080. View

Sullivan M, Nitschke S, Steup M, Minassian B, Nitschke F . Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan. Int J Mol Sci. 2017; 18(8). PMC: 5578133. DOI: 10.3390/ijms18081743. View

Notkins A, Lernmark A . Autoimmune type 1 diabetes: resolved and unresolved issues. J Clin Invest. 2001; 108(9):1247-52. PMC: 209446. DOI: 10.1172/JCI14257. View

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N . Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9 edition. Diabetes Res Clin Pract. 2019; 157:107843. DOI: 10.1016/j.diabres.2019.107843. View

Roesler W, Helgason C, Gulka M, Khandelwal R . Aberrations in the diurnal rhythms of plasma glucose, plasma insulin, liver glycogen, and hepatic glycogen synthase and phosphorylase activities in genetically diabetic (db/db) mice. Horm Metab Res. 1985; 17(11):572-5. DOI: 10.1055/s-2007-1013609. View

Tan X, Sullivan M, Nada S, Deng B, Schulz B, Gilbert R . Proteomic Investigation of the Binding Agent between Liver Glycogen β Particles. ACS Omega. 2018; 3(4):3640-3645. PMC: 6045358. DOI: 10.1021/acsomega.8b00119. View

Liu Q, Zhu Z, Wang M, Wang Y, Zhang P, Wang H . Characterization of glycogen molecular structure in the worm Caenorhabditis elegans. Carbohydr Polym. 2020; 237:116181. DOI: 10.1016/j.carbpol.2020.116181. View

10.

Meyer F, Heilmeyer Jr L, Haschke R, FISCHER E . Control of phosphorylase activity in a muscle glycogen particle. I. Isolation and characterization of the protein-glycogen complex. J Biol Chem. 1970; 245(24):6642-8. View

11.

Roach P, DePaoli-Roach A, Hurley T, Tagliabracci V . Glycogen and its metabolism: some new developments and old themes. Biochem J. 2012; 441(3):763-87. PMC: 4945249. DOI: 10.1042/BJ20111416. View

12.

Sullivan M, Powell P, Witt T, Vilaplana F, Roura E, Gilbert R . Improving size-exclusion chromatography separation for glycogen. J Chromatogr A. 2014; 1332:21-9. DOI: 10.1016/j.chroma.2014.01.053. View

13.

Hu Z, Deng B, Tan X, Gan H, Li C, Nada S . Diurnal changes of glycogen molecular structure in healthy and diabetic mice. Carbohydr Polym. 2018; 185:145-152. DOI: 10.1016/j.carbpol.2018.01.003. View

14.

Adeva-Andany M, Gonzalez-Lucan M, Donapetry-Garcia C, Fernandez-Fernandez C, Ameneiros-Rodriguez E . Glycogen metabolism in humans. BBA Clin. 2016; 5:85-100. PMC: 4802397. DOI: 10.1016/j.bbacli.2016.02.001. View

15.

Wang L, Liu Q, Tan X, Wang Z, Wang M, Wise M . Molecular Structure of Glycogen in Escherichia coli. Biomacromolecules. 2019; 20(7):2821-2829. DOI: 10.1021/acs.biomac.9b00586. View

16.

Sullivan M, Aroney S, Li S, Warren F, Joo J, Mak K . Changes in glycogen structure over feeding cycle sheds new light on blood-glucose control. Biomacromolecules. 2013; 15(2):660-5. DOI: 10.1021/bm401714v. View

17.

Sullivan M, Li J, Li C, Vilaplana F, Stapleton D, Gray-Weale A . Molecular structural differences between type-2-diabetic and healthy glycogen. Biomacromolecules. 2011; 12(6):1983-6. PMC: 3113368. DOI: 10.1021/bm2006054. View

18.

Stumvoll M, Goldstein B, van Haeften T . Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005; 365(9467):1333-46. DOI: 10.1016/S0140-6736(05)61032-X. View

19.

Sullivan M, Vilaplana F, Cave R, Stapleton D, Gray-Weale A, Gilbert R . Nature of alpha and beta particles in glycogen using molecular size distributions. Biomacromolecules. 2010; 11(4):1094-100. DOI: 10.1021/bm100074p. View

20.

MacAulay K, Woodgett J . Targeting glycogen synthase kinase-3 (GSK-3) in the treatment of Type 2 diabetes. Expert Opin Ther Targets. 2008; 12(10):1265-74. PMC: 4485462. DOI: 10.1517/14728222.12.10.1265. View