Objective(s): This study was aimed to investigate the effect of Berberis integerrima (B. integerrima) extract on Insulin sensitivity in high-fructose-fed Insulin-resistant rats. Materials and Methods: Experimental rats were randomly divided into two groups: the control group was fed a regular chow diet while other group fed with a high-fructose diet for 8 weeks. After the first six weeks, the animals were treated with B. integerrima extract or pioglitazone for two weeks. Insulin and adiponectin levels were measured by ELISA. Additionally, Insulin resistance was calculated using a Homeostasis Model Assessment of Insulin resistance (HOMA-IR). The plasma free fatty acid (FFA) profile was obtained by gas chromatography. PPARγ and GLUT4 gene expression were assessed by real-time polymerase chain reaction (PCR) and western-blotting. Results: Comparing the B. integerrima treated group with the control group, weight gain (P=0. 009) and levels of Insulin (P=0. 001), blood glucose (P<0. 0001), and HOMA-IR (P<0. 0001) were significantly reduced. Additionally, the adiponectin concentration was significantly increased (P<0. 0001). Among the FFA fractions, the mean concentration of palmitoleic acid and stearic acid in the B. integerrima group were significantly higher than the control group (P<0. 0001 and P=0. 005, respectively). However, there was no significant difference at the mRNA and protein level of GLUT4 and PPAR-γ between B. integerrima treated group and control group. Conclusion: The study findings revealed that B. integerrima might be a protective candidate against Type 2 diabetes/Insulin resistance through direct Insulin-like effect and an increase in adiponectin levels. However, the mechanism of B. integerrima was independent of GLUT4 and PPARγ .

Objective(s): Diabetes mellitus has been suggested to be the most common metabolic disorder associated with magnesium deficiency. This study aimed to investigate the effects and mechanisms of magnesium supplementation on Insulin receptor activity in elderly type 2 diabetes using a rat model and to provide experimental evidence for Insulin resistance improvement by magnesium supplementation. Materials and Methods: Rat model of type 2 diabetes was developed using a high-fat diet along with low dose streptozotocin (STZ) treatment. Magnesium supplement was given orally by mixing with the high-fat diet. Serum Insulin level, Insulin sensitivity, and Insulin receptor affinity were assessed using radioimmunoassay (RIA). Insulin receptor, Insulin receptor substrate (IRS-2), and β-Arrestin-2 gene and protein expression levels were measured using immunohistochemistry and RT-PCR. Xanthine oxidase assay, thiobarbituric acid reactive substance assay (TCA method), colorimetric assay, and ELISA were used to determine the serum SOD, MDA, T-AOC, and ox-LDL levels, respectively. Results: Magnesium supplementation enhanced Insulin sensitivity and decreased Insulin resistance in diabetic rats mainly through increasing Insulin receptor expression, affinity, and augmenting Insulin receptor signaling. Magnesium supplementation also inhibited lipid peroxidation in diabetic rats and protected against pancreatic cell injury in diabetic rats. In addition, we found that β-arrestin-2 gene expression was suppressed in diabetes, which was possibly attributed to gene methylation modification, as β-arrestin 2 promotor was rich in methylation-regulating sites. Magnesium supplementation could affect β-arrestin-2 gene expression and methylation. Conclusion: Magnesium supplementation has a positive effect on Insulin receptor activity and Insulin sensitivity in type 2 diabetes.