PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance

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

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1423-1432
Number of pages10
JournalJournal of Clinical Investigation
Volume111
Issue number9
DOIs
StatePublished - May 2003
Externally publishedYes

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Gene Deletion
Protein Transport
Glycogen
Insulin Resistance
Protein Phosphatase 1
Glycogen Synthase
Glucose Intolerance
Insulin Receptor
Hyperinsulinism
Adipose Tissue
Myocardium
Skeletal Muscle
Triglycerides
Lipids
Glucose
Muscles

ASJC Scopus subject areas

  • Medicine(all)

Cite this

PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance. / Crosson, Sean M.; Khan, Ahmir; Printen, John; Pessin, Jeffrey E.; Saltiel, Alan R.

In: Journal of Clinical Investigation, Vol. 111, No. 9, 05.2003, p. 1423-1432.

Research output: Contribution to journalArticle

Crosson, Sean M. ; Khan, Ahmir ; Printen, John ; Pessin, Jeffrey E. ; Saltiel, Alan R. / PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 9. pp. 1423-1432.
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