TY - JOUR
T1 - Deletion of muscle IGF-I transiently impairs growth and progressively disrupts glucose homeostasis in male mice
AU - Vassilakos, Georgios
AU - Lei, Hanqin
AU - Yang, Yun
AU - Puglise, Jason
AU - Matheny, Michael
AU - Durzynska, Julia
AU - Ozery, Matan
AU - Bennett, Katherine
AU - Spradlin, Ray
AU - Bonanno, Heather
AU - Park, Soohyun
AU - Ahima, Rexford S.
AU - Barton, Elisabeth R.
N1 - Publisher Copyright:
© The Author(s).
PY - 2019/1
Y1 - 2019/1
N2 - Insulin-like growth factors (IGFs) are essential for local skeletal muscle growth and organismal physiology, but these actions are entwined with glucose homeostasis through convergence with insulin signaling. The objective of thisworkwas to determinewhether the effects of IGF-I on growth andmetabolismcould be separated. Wegeneratedmuscle-specific IGF-I-deficient (MID) mice that afford inducible deletion of Igf1 at any age.After Igf1 deletion at birth or in young adultmice, evaluations ofmuscle physiology and glucose homeostasiswere performed up to 16wk of age.MIDmice generated at birth had lowermuscle and circulating IGF-I,decreasedmuscle and body mass, and impairedmuscle force production. Eight-wk-oldmaleMID had heightened insulin levels with trends of elevated fasting glucose. This phenotype progressed to impaired glucose handling and increased fat deposition without significant musclemass loss at 16wk of age. The same phenotype emerged in 16-wk-oldMIDmice induced at 12 wk of age, compounded with heightened muscle fatigability and exercise intolerance.We assert that muscle IGF-I independently modulates anabolismandmetabolismin an age-dependentmanner, thus positioningmuscle IGF-Imaintenance to be critical for bothmuscle growth andmetabolic homeostasis.
AB - Insulin-like growth factors (IGFs) are essential for local skeletal muscle growth and organismal physiology, but these actions are entwined with glucose homeostasis through convergence with insulin signaling. The objective of thisworkwas to determinewhether the effects of IGF-I on growth andmetabolismcould be separated. Wegeneratedmuscle-specific IGF-I-deficient (MID) mice that afford inducible deletion of Igf1 at any age.After Igf1 deletion at birth or in young adultmice, evaluations ofmuscle physiology and glucose homeostasiswere performed up to 16wk of age.MIDmice generated at birth had lowermuscle and circulating IGF-I,decreasedmuscle and body mass, and impairedmuscle force production. Eight-wk-oldmaleMID had heightened insulin levels with trends of elevated fasting glucose. This phenotype progressed to impaired glucose handling and increased fat deposition without significant musclemass loss at 16wk of age. The same phenotype emerged in 16-wk-oldMIDmice induced at 12 wk of age, compounded with heightened muscle fatigability and exercise intolerance.We assert that muscle IGF-I independently modulates anabolismandmetabolismin an age-dependentmanner, thus positioningmuscle IGF-Imaintenance to be critical for bothmuscle growth andmetabolic homeostasis.
KW - Diabetes
KW - Exercise intolerance
KW - Force generation
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U2 - 10.1096/fj.201800459R
DO - 10.1096/fj.201800459R
M3 - Article
C2 - 29932867
AN - SCOPUS:85059225452
SN - 0892-6638
VL - 33
SP - 181
EP - 194
JO - FASEB Journal
JF - FASEB Journal
IS - 1
ER -