PMC

Apocynin prevents oleate-induced beta cell dysfunction ex vivo in islets isolated from rats. (a) Insulin secretory response to glucose and (b) islet insulin content in freshly isolated islets of rats treated as described in the Fig.  legend. Data are means ± SEM (saline [SAL], n = 7; oleate [OLE], n = 7; OLE + apocynin [APO], n = 7; APO, n = 8); **p < 0.01 OLE vs SAL; ^‡ p < 0.05 OLE vs all

The genetic deletion of p47^phox in mice prevents oleate-induced beta cell dysfunction ex vivo in isolated islets. (a) Insulin secretory response to glucose and (b) islet insulin content in freshly isolated islets of p47^phox-null mice (KO) and their WT littermate controls treated as described in the Fig.  legend. Data are means ± SEM (WT-saline [SAL], n = 8; WT-oleate [OLE], n = 7; KO-OLE, n = 7; KO-SAL, n = 6); **p < 0.01 KO-OLE vs WT-SAL, ^‡‡ p < 0.01 WT-OLE vs all

Apocynin prevents the decrease in beta cell function induced by oleate in vivo during two-step hyperglycaemic clamp in rats. Rats were treated as described in the Fig.  legend. Plasma levels of NEFA (a), glucose (b), insulin (d) and C-peptide (e) and glucose infusion rate (Ginf) (c) were measured during the two-step hyperglycaemic clamp. Data are means ± SEM (saline [SAL], n = 8; oleate [OLE], n = 8; OLE + apocynin [APO], n = 5; APO, n = 7); **p < 0.01 OLE vs SAL, ***p < 0.001 OLE vs SAL, ^† p < 0.05 OLE vs OLE + APO, ^‡‡ p < 0.01 OLE vs all. White circles, SAL; black circles, OLE; black squares, OLE + APO; white squares, APO

The genetic deletion of p47^phox in mice normalises total superoxide and total ROS levels increased by oleate in islets. p47^phox-null mice (KO) and their WT littermate controls were treated for 48 h with saline (SAL, 0.5 μl/min) or oleate (OLE, 0.4 μmol/min) to elevate plasma NEFA 1.5- to twofold. Total (a) and mitochondrial (b) superoxide levels (WT-saline [SAL], n = 7; WT-oleate [OLE], n = 6; KO-OLE, n = 6; KO-SAL, n = 4) and total ROS (c) levels (WT-SAL, n = 6; WT-OLE, n = 6; KO-OLE, n = 7; KO-SAL, n = 3) in freshly isolated islets of the mice treated as above. Data are expressed as mean % of SAL ± SEM; ^‡‡ p < 0.01 WT-OLE vs all. The representative fluorescent images of islets imaged with HEt, MitoSOX and H₂DCF-DA are also shown

The NADPH oxidase inhibitor apocynin normalises NADPH oxidase activity, total superoxide, total ROS and MDA levels increased by oleate in rat islets. Rats were treated for 48 h with saline (SAL, 5 μl/min); oleate, to elevate plasma NEFA 1.5- to twofold (OLE, 1.3 μmol/min); oleate + apocynin (OLE + APO, 1.3 μmol/min + 0.5 μmol kg⁻¹ min⁻¹, respectively) or apocynin (APO, 0.5 μmol kg⁻¹ min⁻¹). (a) NADPH oxidase activity in freshly isolated islets of the rats treated as above. Data are means ± SEM (SAL, n = 7; OLE, n = 9; OLE + APO, n = 6; APO, n = 6). (b) NADPH/NADP⁺ in freshly isolated islets of the rats treated as above. Data are means ± SEM (n = 6 per group). Total (c) and mitochondrial (d) superoxide levels (n = 6 rats per group) and total ROS (e) levels (n = 4 rats per group) in freshly isolated islets of rats treated as above. Data are expressed as mean % of SAL ± SEM. The representative fluorescent images of islets stained with hydroethidine, MitoSOX and H₂DCF-DA are also shown. (f) MDA levels in freshly isolated islets of rats treated as described above. Data are means ± SEM (SAL, n = 7; OLE, n = 8; OLE + APO, n = 9; APO, n = 9); *p < 0.05 OLE vs SAL, **p < 0.01 OLE vs SAL, ^† p < 0.05 OLE vs OLE + APO and APO, ^†† p < 0.01 OLE vs OLE + APO and APO, ^‡‡ p < 0.01 OLE vs all