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

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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PTG+/– mice display glucose intolerance, moderate hyperinsulinemia, and ...
PTG+/– mice display glucose intolerance, moderate hyperinsulinemia, and insulin resistance with aging. (a) Fasting PTG+/– mice display the development of glucose intolerance with aging. Male animals fasted for 16 hours overnight were used for glucose tolerance experiments (n = 4–12 per group). Results are reported as mean ± SEM. (*P ≤ 0.05; **P ≤ 0.005; ***P ≤ 0.0002). Age of animals is shown at upper right of each graph. (b) Serum insulin levels of PTG+/– mice are elevated in the fasting state and in response to a glucose bolus during the intraperitoneal glucose tolerance test. Insulin levels were measured from additional sera collected at the time of the intraperitoneal glucose tolerance tests (n = 4–12 group). Results are reported as mean ± SEM (*P ≤ 0.05; **P ≤ 0.02; ***P ≤ 0.005). (c) Nonfasting PTG+/– mice display moderate insulin resistance at 12 months of age. Male animals in the nonfasting state were used for insulin tolerance experiments (n = 4–12 per group). Results are reported as mean ± SEM (*P ≤ 0.002; **P ≤ 0.001; ***P ≤ 0.0005).