Carbohydrate-Induced Insulin Signaling Activates Focal Adhesion Kinase: A Nutrient and Mechanotransduction Crossroads

Abstract

Research has suggested that nutrient, exercise, and metabolism-related proteins interact to regulate mammalian target of rapamycin complex one (mTOR) post-exercise and their interactions needs clarification. In a double-blind, cross-over, repeated measures design, ten participants completed four sets to failure at 70% of 1-repitition maximum (1-RM) with 45 s rest on angled leg press with or without pre-exercise maltodextrin (2 g/kg) after a 3 h fast. Vastus lateralis biopsies were collected at baseline before supplementation and 1 h post-exercise to analyze Focal Adhesion Kinase (FAK), ribosomal protein S6 kinase beta-1 (p70S6K), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and 5' AMP-activated protein kinase (AMPK) activation. FAK and IRS-1 activity were only elevated 1 h post-exercise with carbohydrate ingestion (p < 0.05). PI3K and p70S6K activation were both elevated after exercise in both conditions (p < 0.05). However, AMPK activity did not change from baseline in both conditions (p > 0.05). We conclude that FAK does not induce mTOR activation through PI3K crosstalk in response to exercise alone. In addition, FAK may not be regulated by AMPK catalytic activity, but this needs further research. Interestingly, carbohydrate-induced insulin signaling appears to activate FAK at the level of IRS-1 but did not enhance mTOR activity 1 h post-exercise greater than the placebo condition. Future research should investigate these interactions under different conditions and within different time frames to clearly understand the interactions between these signaling molecules.

Keywords: crosstalk; focal adhesion kinase; insulin; insulin receptor substrate 1 (IRS-1); mammalian target of rapamycin complex one (mTOR); mechanotransduction; phosphatidylinositol 3-kinase (PI3K).

Figure 1

Changes in focal adhesion kinase (FAK) phosphorylation at Tyr³⁹⁷ for each time point and condition relative to total protein content are illustrated. There was a significant interaction showing a greater increase in FAK Tyr³⁹⁷phosphorylation 1 h post-exercise (**). In addition, there was a significant condition effect showing carbohydrate supplementation increased FAK Tyr³⁹⁷ phosphorylation greater than the placebo condition (*).

Figure 2

Changes in total amount of ribosomal protein S6 kinase beta-1 (p70S6K) phosphorylated at Thr³⁸⁹ for each timepoint and condition relative to total protein content are illustrated. There was a significant time effect showing increases in p70S6K Thr³⁸⁹ phosphorylation from pre-exercise to 1 h post-exercise (*).

Figure 3

Changes in total amount of activated insulin receptor substrate-1 (IRS-1) ^panTyr for each time point and condition relative to total protein content are illustrated. There was an interaction effect showing a significant increase in IRS-1 phosphorylation in the carbohydrate condition at 1 h post-exercise compared to the placebo (*). No change in IRS-1 (^panTyr) was observed for the placebo condition.

Figure 4

Changes in total amount of activated phosphatidylinositol 3-kinase (PI3K) p110 subunit in for pre-exercise and 1 h post-exercise with or without carbohydrate supplementation relative to total protein content are illustrated. There was a significant increase in PI3K activation across time for both conditions (*).