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A novel mechanism for the insulin‐sensitizing effect of leucine in adipocytes
Author(s) -
Halim Vera,
Guo Xin,
Li Honggui,
Wu Chaodong
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.351.2
Leucine supplementation improves glycemic control and decreases adipose tissue inflammation in mouse models of diet‐induced obesity and type 2 diabetes. However, the mechanisms underlying the beneficial effects of leucine remain to be elucidated. The objective of this study is to define how leucine improves adipocyte insulin signaling. In cultured 3T3‐L1 adipocytes, palmitate caused a decrease in insulin‐induced Akt phosphorylation, demonstrating a role for overnutrition in inducing adipocyte insulin resistance. Upon supplementation of leucine, palmitate‐induced adipocyte insulin resistance was completely reversed, indicating an insulin‐sensitizing effect of leucine in adipocytes. Because PFKFB3/iPFK2 is a master regulator of adipocyte nutrient metabolism that governs adipocyte insulin signaling, we then determined the involvement of PFKFB3/iPFK2 in the insulin‐sensitizing effect of leucine and found that PFKFB3/iPFK2 knockdown caused a marked decrease in insulin‐induced Akt phosphorylation in cultured 3T3‐L1 adipocytes. More importantly, knockdown of PFKFB3/iPFK2 nearly abolished the insulin‐sensitizing effect of leucine. Together, these data suggest a novel mechanism for the insulin‐sensitizing effect of leucine. In this novel mechanism, PFKFB3/iPFK2 is critically involved in the effect of leucine on stimulating adipocyte insulin signaling. Grant Funding Source : ADA Junior Faculty Award