Fig. 8: Inhibition of S6 kinase prevents the effects of chronic hyperglycaemia on oxidative metabolism. | Nature Communications

Fig. 8: Inhibition of S6 kinase prevents the effects of chronic hyperglycaemia on oxidative metabolism.

From: Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells

Fig. 8

a Oxygen-consumption rate (OCR) of LG- and HG-cells cultured for 48 h ± 10 µM S6-kinase inhibitor PF-4708671 (S6Ki). OCR is expressed as the percentage change from the OCR baseline (2 mM glucose) following sequential addition of 20 mM glucose (20 G), 1 μM oligomycin (Oligo) and 0.5 μM rotenone + 0.5 μM antimycin A (Rot + Ant) (n = 5 biologically independent experiments per group). LG-cells (black), HG-cells (red), LG-cells+S6Ki (blue), HG-cells+S6Ki (orange). b Percentage change in OCR when glucose was raised from 2 mM to 20 mM (20 G, n = 5 replicates/group), ATP-linked OCR (Oligo), OCR required to maintain the mitochondrial leak (Rot + Ant) and non-mitochondrial OCR (non-mito) (n = 5 replicates/group). Same data as in (a). c OCR in control and diabetic islets cultured for 48 h ± 10 µM S6Ki. OCR is expressed as the percentage change from the OCR baseline (2 mM glucose) and after sequential addition of 20 mM glucose (20 G), 5 μM oligomycin (Oligo) and 5 μM rotenone + 5 µM antimycin A (Rot + Ant). Control islets (black, n = 7 mice examined over seven independent experiments), Diabetic islets (red, n = 7 animals examined over seven independent experiments), Control islets + S6Ki (blue, n = 7 mice examined over ten independent experiments), Diabetic islets + S6Ki (orange, n = 7 mice examined over 8 independent experiments). d Percentage change in OCR of control and diabetic islets when glucose was raised from 2 mM to 20 mM (20 G), ATP-linked OCR (Oligo), OCR required to maintain the mitochondrial leak (Rot + Ant) and non-mitochondrial OCR (non-mito). Same data as in (c). e Basal OCR at 2 mM glucose in LG- and HG-cells cultured for 48 h ± 10 µM S6Ki (n = 5 biologically independent experiments per group). f Basal OCR at 2 mM glucose in control and diabetic islets cultured for 48 h ± 10 µM S6Ki Control islets (black, n = 7 mice examined over seven independent experiments), Diabetic islets (red, n = 7 animals examined over seven independent experiments), Control islets + S6Ki (blue, n = 7 mice examined over ten independent experiments), Diabetic islets + S6Ki (orange, n = 7 mice examined over 8 independent experiments). All panels show individual data points and mean ± sem. *P < 0.05, **P < 0.01, ***P < 0.001. ± s.e.m. two-tailed unpaired Student’s t test. Veh, vehicle (0.05% DMSO). Source data are provided as a Source Data file.

Back to article page