Glutamine Regulates Skeletal Muscle Immunometabolism in Type 2 Diabetes
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Glutamine Regulates Skeletal Muscle Immunometabolism in Type 2 Diabetes. / Dollet, Lucile; Kuefner, Michael; Caria, Elena; Rizo-Roca, David; Pendergrast, Logan; Abdelmoez, Ahmed M; Karlsson, Håkan Kr; Dalbram, Emilie; Treebak, Jonas; Harada, Jun; Näslund, Erik; Rydén, Mikael; Zierath, Juleen R; Pillon, Nicolas J; Krook, Anna.
In: Diabetes, Vol. 71, No. 4, 2022, p. 624-636.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Glutamine Regulates Skeletal Muscle Immunometabolism in Type 2 Diabetes
AU - Dollet, Lucile
AU - Kuefner, Michael
AU - Caria, Elena
AU - Rizo-Roca, David
AU - Pendergrast, Logan
AU - Abdelmoez, Ahmed M
AU - Karlsson, Håkan Kr
AU - Dalbram, Emilie
AU - Treebak, Jonas
AU - Harada, Jun
AU - Näslund, Erik
AU - Rydén, Mikael
AU - Zierath, Juleen R
AU - Pillon, Nicolas J
AU - Krook, Anna
N1 - © 2022 by the American Diabetes Association.
PY - 2022
Y1 - 2022
N2 - Dysregulation of skeletal muscle metabolism influences whole body insulin sensitivity and glucose homeostasis. We hypothesized that type 2 diabetes-associated alterations in the plasma metabolome directly contributes to skeletal muscle immunometabolism and the subsequent development of insulin resistance. To this end, we analyzed the plasma and skeletal muscle metabolite profile and identified glutamine as a key amino acid that was inversely correlating with body mass index (BMI) and HOMA-IR index in people with normal glucose tolerance or type 2 diabetes. Using an in vitro model of human myotubes and an in vivo model of diet-induced obesity and insulin resistance in mice, we provide evidence that glutamine levels directly influence the inflammatory response of skeletal muscle and regulates the expression of the adaptor protein GRB10, an inhibitor of insulin signaling. Moreover, we demonstrate that a systemic increase of glutamine levels in a mouse model of obesity improves insulin sensitivity and restores glucose homeostasis. We conclude that glutamine supplementation may represent a potential therapeutic strategy to prevent or delay the onset of insulin resistance in obesity by reducing inflammatory markers and promoting skeletal muscle insulin sensitivity.
AB - Dysregulation of skeletal muscle metabolism influences whole body insulin sensitivity and glucose homeostasis. We hypothesized that type 2 diabetes-associated alterations in the plasma metabolome directly contributes to skeletal muscle immunometabolism and the subsequent development of insulin resistance. To this end, we analyzed the plasma and skeletal muscle metabolite profile and identified glutamine as a key amino acid that was inversely correlating with body mass index (BMI) and HOMA-IR index in people with normal glucose tolerance or type 2 diabetes. Using an in vitro model of human myotubes and an in vivo model of diet-induced obesity and insulin resistance in mice, we provide evidence that glutamine levels directly influence the inflammatory response of skeletal muscle and regulates the expression of the adaptor protein GRB10, an inhibitor of insulin signaling. Moreover, we demonstrate that a systemic increase of glutamine levels in a mouse model of obesity improves insulin sensitivity and restores glucose homeostasis. We conclude that glutamine supplementation may represent a potential therapeutic strategy to prevent or delay the onset of insulin resistance in obesity by reducing inflammatory markers and promoting skeletal muscle insulin sensitivity.
U2 - 10.2337/db20-0814
DO - 10.2337/db20-0814
M3 - Journal article
C2 - 35040927
VL - 71
SP - 624
EP - 636
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 4
ER -
ID: 290599551