Fig 2: RB ameliorated insulin resistance by upregulating the PI3K/AKT/TXNIP cascade signaling pathway in vitro. (A) Effect of MAN on the expression of p-PI3K, PI3K, p-AKT, AKT, and TXNIP proteins in C2C12 and HepG2 cells; (B) Effect of RB on the expression of p-PI3K, PI3K, p-AKT, AKT, and TXNIP proteins in HepG2 cells; (C) Effect of RB on the expression of p-PI3K, PI3K, p-AKT, AKT, and TXNIP proteins in C2C12 cells; (D) Effect of PI3K inhibitor LY294002 (20 µM) on the expression of p-PI3K, PI3K, p-AKT, AKT, and TXNIP proteins in HepG2 cells; (E) Effect of PI3K inhibitor LY294002 (20 µM) on the expression of p-PI3K, PI3K, p-AKT, AKT, and TXNIP proteins in C2C12 cells. All data are expressed as the mean ± SD of three independent experiments. # p < 0.05, ## p < 0.01, vs. NC group; * p < 0.05, ** p < 0.01, vs. DM control group; $ p < 0.05, $$ p < 0.01, vs. RSG group; ^ p < 0.05, ^^ p < 0.01, vs. BBR group; ! p < 0.05, !! p < 0.01, vs. MIX group; & p < 0.05, && p < 0.01, vs. RB group; ns, no significance.

Fig 3: Schematic representation of the duality of TXNIP function as it pertains to peritoneal carcinomatosis/sarcomatosis

Fig 4: Schematic illustration of the protective effects of bFGF on HUVECs under HG + PA conditions. Diabetes-induced endothelial impairment can be attributed mainly to the dysfunction of S-nitrosylation homeostasis (S-nitrosylation of IKKßC179 and p65C38) and resultant upregulation of chronic inflammation. Mechanistically, the up-regulation of S-nitrosylated IKKßC179 and p65C38 by bFGF were attributed to the synergy between eNOS and Trx activity. In addition, the bFGF-mediated disassociation between Txnip and Trx in a NO-independent manner, also benefited the cellular redox homeostasis and maintaining the content of S-nitrosylated IKKßC179 and p65C38 in endothelial cells. This finding could yield new therapeutic insights into the prevention and treatment of diabetes-associated vascular disease.

Fig 5: Lipidomics analysis of BAT showing less PUFA in KO (n = 8, males)(A–E) Total fatty acid acyl-chain species (A), acyl-chain composition of TAG (B), PC (C), and PE (D), and total acyl-chain (E) of isolated mitochondria from BAT of TXNIP WT and KO animals at RT on control diet. Only the most abundant species are shown for clarity.(F) Membrane fluidity measured as Laurdan general polarization in isolated mitochondria from WT and KO on the control and ketogenic diet.(G–J) Total acyl-chain species (G), acyl-chain composition of TAG (H), PC (I), and PE (J) of WT and KO BAT on a ketogenic diet.(K–O) Total acyl-chain (K), acyl-chain composition of TAG (L), PC (M), PE (N), and cardiolipin (O) of WT and KO heart on the control diet. *p = 0.01 < p < 0.05; **p = 0.001 < p = 0.01; ***p = 0.001