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Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen.

Publication ,  Journal Article
O'Doherty, RM; Jensen, PB; Anderson, P; Jones, JG; Berman, HK; Kearney, D; Newgard, CB
Published in: J Clin Invest
February 2000

Glycogen-targeting subunits of protein phosphatase-1, such as protein targeting to glycogen (PTG), direct the phosphatase to the glycogen particle, where it stimulates glycogenesis. We have investigated the metabolic impact of overexpressing PTG in liver of normal rats. After administration of PTG cDNA in a recombinant adenovirus, animals were fasted or allowed to continue feeding for 24 hours. Liver glycogen was nearly completely depleted in fasted control animals, whereas glycogen levels in fasted or fed PTG-overexpressing animals were 70% higher than in fed controls. Nevertheless, transgenic animals regulated plasma glucose, triglycerides, FFAs, ketones, and insulin normally in the fasted and fed states. Fasted PTG-overexpressing animals receiving an oral bolus of [U-(13)C]glucose exhibited a large increase in hepatic glycogen content and a 70% increase in incorporation of [(13)C]glucose into glycogen. However, incorporation of labeled glucose accounted for only a small portion of the glycogen synthesized in PTG-overexpressing animals, consistent with our earlier finding that PTG promotes glycogen synthesis from gluconeogenic precursors. We conclude that hepatic PTG overexpression activates both direct and indirect pathways of glycogen synthesis. Because of its ability to enhance glucose storage without affecting other metabolic indicators, the glycogen-targeting subunit may prove valuable in controlling blood glucose levels in diabetes.

Duke Scholars

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

February 2000

Volume

105

Issue

4

Start / End Page

479 / 488

Location

United States

Related Subject Headings

  • Triglycerides
  • Recombinant Proteins
  • Rats, Wistar
  • Rats
  • Male
  • Liver Glycogen
  • Liver
  • Ketones
  • Intracellular Signaling Peptides and Proteins
  • Insulin
 

Citation

APA
Chicago
ICMJE
MLA
NLM
O’Doherty, R. M., Jensen, P. B., Anderson, P., Jones, J. G., Berman, H. K., Kearney, D., & Newgard, C. B. (2000). Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen. J Clin Invest, 105(4), 479–488. https://doi.org/10.1172/JCI8673
O’Doherty, R. M., P. B. Jensen, P. Anderson, J. G. Jones, H. K. Berman, D. Kearney, and C. B. Newgard. “Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen.J Clin Invest 105, no. 4 (February 2000): 479–88. https://doi.org/10.1172/JCI8673.
O’Doherty RM, Jensen PB, Anderson P, Jones JG, Berman HK, Kearney D, et al. Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen. J Clin Invest. 2000 Feb;105(4):479–88.
O’Doherty, R. M., et al. “Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen.J Clin Invest, vol. 105, no. 4, Feb. 2000, pp. 479–88. Pubmed, doi:10.1172/JCI8673.
O’Doherty RM, Jensen PB, Anderson P, Jones JG, Berman HK, Kearney D, Newgard CB. Activation of direct and indirect pathways of glycogen synthesis by hepatic overexpression of protein targeting to glycogen. J Clin Invest. 2000 Feb;105(4):479–488.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

February 2000

Volume

105

Issue

4

Start / End Page

479 / 488

Location

United States

Related Subject Headings

  • Triglycerides
  • Recombinant Proteins
  • Rats, Wistar
  • Rats
  • Male
  • Liver Glycogen
  • Liver
  • Ketones
  • Intracellular Signaling Peptides and Proteins
  • Insulin