Figures & data
Figure 1. Adipocyte SWELL1 is a positive regulator of insulin signalling and glucose homeostasis. LRR: Leucine Rich Repeat; Cav1: Caveolin-1; GSK3β: Glycogen Synthase 3β; GS: Glycogen Synthase. (Zhang Y. et al., Nature Cell Biology 2017).
Figure 2. SWELL1-mediated VRAC activation by mechanical adipocyte swelling. Mechanical swelling increases adipocyte size without a measurable change in total surface area (as assessed by total cell capacitance) implicating caveolae flattening as a mechanism of VRAC activation in adipocytes. LRR: Leucine Rich Repeat; Cav1: Caveolin-1.
Figure 3. Adipocyte SWELL1/VRAC complex regulates insulin-GRB2-PI3K-AKT2 signalling and senses mechanical forces via caveolae flattening to tune insulin-AKT2 signalling by modulating GRB2-IRS1 interactions. (a) In WT adipocytes, SWELL1 restrains GRB2 from suppression of PI3K-AKT2 signalling. (b) SWELL1 ablation releases GRB2 to fully inhibit insulin-PI3K-AKT2 signalling. (c) GRB2 knock-down (KD) in SWELL1 KO adipocytes fully rescues insulin-PI3K-AKT2 signalling. (d) Working model: adipocyte expansion activates the SWELL1/VRAC complex to disinhibit insulin-PI3K-AKT2 via GRB2, and thereby support lipogenesis and continued adipocyte growth, in a feed-forward manner, potentiating adipocyte hypertrophy.
