PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance.
Protein targeting to glycogen (PTG) is a scaffolding protein that targets protein phosphatase 1alpha (PP1alpha) 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.
Crosson
Sean M
SM
Department of Medicine, Life Sciences Institute, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-0650, USA.
Khan
Ahmir
A
Printen
John
J
Pessin
Jeffrey E
JE
Saltiel
Alan R
AR
D000375:Aging / Q000502:physiology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010749:Phosphoprotein Phosphatases; D015398:Signal Transduction / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
D002352:Carrier Proteins; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; C491294:PPP1R3C protein, human; C104748:Ppp1r3c protein, mouse; D014280:Triglycerides; D006003:Glycogen; D005934:Glucagon; D006006:Glycogen Synthase; D010749:Phosphoprotein Phosphatases; D005947:Glucose