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PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance
Sean M. Crosson, … , Jeffrey E. Pessin, Alan R. Saltiel
Sean M. Crosson, … , Jeffrey E. Pessin, Alan R. Saltiel
Published May 1, 2003
Citation Information: J Clin Invest. 2003;111(9):1423-1432. https://doi.org/10.1172/JCI17975.
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Article Metabolism

PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance

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Abstract

Protein targeting to glycogen (PTG) is a scaffolding protein that targets protein phosphatase 1α (PP1α) to glycogen, and links it to enzymes involved in glycogen synthesis and degradation. We generated mice that possess a heterozygous deletion of the PTG gene. These mice have reduced glycogen stores in adipose tissue, liver, heart, and skeletal muscle, corresponding with decreased glycogen synthase activity and glycogen synthesis rate. Although young PTG heterozygous mice initially demonstrate normal glucose tolerance, progressive glucose intolerance, hyperinsulinemia, and insulin resistance develop with aging. Insulin resistance in older PTG heterozygous mice correlates with a significant increase in muscle triglyceride content, with a corresponding attenuation of insulin receptor signaling. These data suggest that PTG plays a critical role in glycogen synthesis and is necessary to maintain the appropriate metabolic balance for the partitioning of fuel substrates between glycogen and lipid.

Authors

Sean M. Crosson, Ahmir Khan, John Printen, Jeffrey E. Pessin, Alan R. Saltiel

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Figure 1

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Mice possessing a heterozygous deletion of the PTG gene display reduced ...
Mice possessing a heterozygous deletion of the PTG gene display reduced PTG protein levels while the expression of GL and GM are not altered. (a) The entire 1-kb coding region of the intronless PTG gene was targeted for disruption. PTG heterozygous mice were generated as outlined in Methods and then backcrossed for five generations to inbred C57BL/6J mice. (b) PTG protein levels are reduced in insulin-responsive tissues of PTG+/– mice. Tissue homogenates were prepared from nonfasted 1- to 2-month-old male animals and analyzed by Western blotting. Equivalent loading was insured by analysis of the levels of the basal transcription factor TFIIEα. (c) The expression levels of the tissue-specific glycogen-targeting subunits GM and GL are unchanged in PTG heterozygous mice. The expression level of GL at the mRNA level was analyzed by RT-PCR using liver total RNA isolated from nonfasting 1- to 2-month-old male animals. The expression of GM was analyzed by Western blotting and equivalent loading was insured by analysis of the levels of TFIIEα.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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