Effects of allyl isothiocyanate on insulin resistance, oxidative stress status, and transcription factors in high‐fat diet/streptozotocin‐induced type 2 diabetes mellitus in rats

Abstract

Allyl isothiocyanate (AITC), a dietary phytochemical found in some cruciferous vegetables, is commonly used as an antimicrobial, anticancer, and antioxidant agent.In the present study, we investigated the effects of AITC on insulin resistance and transcription factors in a diabetic rat model. A total of 42 Wistar rats were divided into six groups and orally treated for 12 weeks as follows: (i) control; (ii) AITC (100 mg/kg body weight [BW]); (iii) high fat diet (HFD); (iv) HFD + AITC (100 mg/kg BW); (v) HFD + streptozotocin (STZ, 40 mg/kg BW); and (vi) HFD + STZ + AITC.Administration of AITC reduced blood glucose, total cholesterol, triglycerides, and creatinine levels, but increased (P < 0.001) total antioxidant capacity. In AITC-treated rats, the glucose transporter-2, peroxisome proliferator-activated receptor gamma, p-insulin receptor substrate-1, and nuclear factor erythroid-derived 2 in the liver and kidney were increased while nuclear factor-kappa B was downregulated (P < 0.05). In conclusion, AITC possesses antidiabetic, antioxidant, and anti-inflammatory activities in HFD/STZ-induced T2DM in rats. These findings may further justify the importance of AITC in phytomedicine. K E Y W O R D Sallyl isothiocyanate, diabetes, insulin resistance, oxidative stress, streptozotocin

Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review

“…Other corroborating evidences are the increased inflammatory markers (NF-κB, TNFα, IL-6, and IL-10) reported in cortical tissues of murine diabetes models [201][202][203], HK2 cell cultures under high glucose environment (NF-κB) [204], and cortical portions of T2D patients (NF-κB) [202]. These elevated markers were associated with disrupted insulin signalling characterized by high FOXO1 and reduced AKT [202], PPARγ, and ISRS1 [201,203] but maintained ISR2 levels [201]. Increased renal gluconeogenesis [202], as expected, and reduced GLUT2 [203] were also associated with enhanced inflammatory markers.…”

“…These elevated markers were associated with disrupted insulin signalling characterized by high FOXO1 and reduced AKT [202], PPARγ, and ISRS1 [201,203] but maintained ISR2 levels [201]. Increased renal gluconeogenesis [202], as expected, and reduced GLUT2 [203] were also associated with enhanced inflammatory markers.…”

“…It was reported that insulin raises SGLT2 protein availability and activity independently of glucose and additionally regulates SGLT2i bioavailability [140][141][142]. Differences in IRec density along the nephron [46] and in the type of IRS expressed in diverse tubule segments, or the same segment but under distinct insulin sensitivity [27,191,[199][200][201]203], point to a renal site-specific selective insulin action and, possibly, to a spatial selective insulin resistance.…”

Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus

“…Additionally, Abdulmalek and Balbaa in 2019 examined the potential of selenium and found that it promoted insulin sensitivity by ameliorating inflammation and oxidative stress in diabetic rats [140]. These data complement the results of basic studies suggesting oxidative stress induces insulin resistance and DM [97,123,132,137,139,140]. Whilst relatively few, there is clinical evidence supporting the animal studies [141].…”

“…One study with a randomized double-blind placebo-controlled design. 6 Oxidative Medicine and Cellular Longevity and inflammatory responses in diabetic rats [139]. Additionally, Abdulmalek and Balbaa in 2019 examined the potential of selenium and found that it promoted insulin sensitivity by ameliorating inflammation and oxidative stress in diabetic rats [140].…”