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. 2022 Nov 14;13:6754. doi: 10.1038/s41467-022-34095-x

Fig. 1. Inhibition of glucokinase prevents the effects of chronic hyperglycaemia.

Fig. 1

a Schematic showing how mannoheptulose (MH) inhibits glucose metabolism. b, c Insulin secretion (b) and insulin content (c) in LG-cells and HG-cells cultured for 48 h ± 10 mM mannoheptulose (MANNO) and then stimulated with 2 mM or 20 mM glucose. Mannoheptulose was omitted during the assay (n = 3 biologically independent experiments). d Oxygen-consumption rate (OCR) in LG-cells and HG-cells cultured for 48 h ± 10 mM MANNO. OCR was recorded at 2 mM glucose and after sequential addition of 20 mM glucose (20 G), 1 μM oligomycin (Oligo) and 0.5 μM rotenone + 0.5 μM antimycin A (Rot + Ant). Data are expressed as the percentage change from baseline (2 mM glucose); n = 10 biologically independent experiments per group. e Percentage change in OCR when glucose was raised from 2 to 20 mM (20 G), ATP-linked OCR (Oligo), OCR required to maintain the mitochondrial leak (Rot + Ant) and non-mitochondrial OCR (non-mito); n = 10 biologically independent experiments per group. Same data as in (d). f, g mRNA levels of the indicated genes involved in glycolytic (f) and mitochondrial (g) metabolism as assessed by qPCR in LG-cells and HG-cells cultured for 48 h ± 10 mM mannoheptulose (Pdk1, Idh2 and Ndufs8, n = 6 biologically independent experiments; Ndufa4, n = 4 biologically independent experiments; Pfkl, Pfkfb3, Eno1, Sdha and Mdh2, n = 3 biologically independent experiments; Aldob, n = 6 biologically independent experiments for LG and HG but n = 5 for LG + MANNO and HG + MANNO; Ndufs8, n = 6 biologically independent experiments for LG but n = 3 for LG + MANNO, HG and HG + MANNO). All panels show individual data points and mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001; two-tailed unpaired Student’s t test. LG-cells (black), HG-cells (red), LG-cells + mannoheptulose (blue), HG-cells + mannoheptulose (orange). Source data are provided as a Source Data file.