Jiangzhi Capsule improves fructose-induced insulin resistance in rats: Association with repair of the impaired sarcolemmal glucose transporter-4 recycling.

Jiangzhi Capsule, originated from an experienced formula in traditional Chinese Medicine, has been listed and used for the management of metabolic abnormalities in Australia for a long time. To better understand Jiangzhi Capsule, this study investigated its effect on insulin resistance. Male rats were treated with liquid fructose in their drinking water over 14 weeks. Jiangzhi Capsule was co-administered (once daily, by oral gavage) during the last 7 weeks. Indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by real-time PCR, Western blot and/or immunohistochemistry. Treatment with Jiangzhi Capsule (100mg/kg) attenuated fructose overconsumption-induced increases in basal plasma insulin concentrations, the homeostasis model assessment of insulin resistance index and the adipose tissue insulin resistance index in rats. The increased plasma glucose concentrations during oral glucose tolerance test were also inhibited. Furthermore, Jiangzhi Capsule had a trend to attenuate the decreased ratios of glucose and non-esterified fatty acids to plasma insulin concentrations. Mechanistically, this insulin-sensitizing action was accompanied by normalization of the downregulated sarcolemmal glucose transporter (GLUT)-4 protein expression and the decreased phosphorylated Akt to total Akt protein ratio in gastrocnemius. These results suggest that Jiangzhi Capsule ameliorates fructose-induced insulin resistance with a link to repair of the impaired sarcolemmal GLUT-4 recycling through modulation of the ratio of phosphorylated Akt to total Akt in gastrocnemius. Our findings provide an evidence-based and mechanistic understanding of Jiangzhi Capsule for the management of insulin resistance-associated disorders.

Jiang L ，Yao L ，Yang Y ，Ke D ，Batey R ，Wang J ，Li Y ... -  《-》

Treatment of rats with Jiangzhi Capsule improves liquid fructose-induced fatty liver: modulation of hepatic expression of SREBP-1c and DGAT-2.

Zhao Y ，Pan Y ，Yang Y ，Batey R ，Wang J ，Li Y ... -  《Journal of Translational Medicine》

Treatment with Rhodiola crenulata root extract ameliorates insulin resistance in fructose-fed rats by modulating sarcolemmal and intracellular fatty acid translocase/CD36 redistribution in skeletal muscle.

Chen T ，Yao L ，Ke D ，Cao W ，Zuo G ，Zhou L ，Jiang J ，Yamahara J ，Li Y ，Wang J ... -  《BMC Complementary and Alternative Medicine》

Mitigation of Insulin Resistance by Mangiferin in a Rat Model of Fructose-Induced Metabolic Syndrome Is Associated with Modulation of CD36 Redistribution in the Skeletal Muscle.

Mangiferin is one of the prominent active components responsible for the antidiabetic property of many traditional herbs, but its underlying mechanisms of action remain unclear. CD36 in skeletal muscle is known to contribute to the etiology of insulin resistance by facilitating fatty acid uptake. This study investigated the effect of mangiferin on insulin resistance. The results showed that treatment of Wistar-Kyoto rats with mangiferin (15 mg/kg, once daily, by oral gavage) for 7 weeks inhibited chronic liquid fructose consumption-induced increases in plasma insulin concentrations at the baseline and during oral glucose tolerance test (OGTT), and the homeostasis model assessment of insulin resistance index. It also suppressed the increases in fasted plasma nonesterified fatty acid (NEFA) concentration and the adipose tissue insulin resistance index. Mechanistically, mangiferin neither affected intakes of fructose and chow, and the increase in epididymal and perirenal fat, nor attenuated fructose-induced hypertension. In contrast, mangiferin attenuated fructose-induced acceleration of plasma NEFA clearance during OGTT, and tended to decrease excessive triglyceride accumulation in gastrocnemius. Immunofluorescence staining and subsequent rating of CD36-expressing fibers in gastrocnemius revealed that mangiferin restored fructose-stimulated sarcolemmal CD36 overexpression and decreased intracellular CD36 distribution. In addition, the effects of mangiferin on the parameters associated with insulin resistance and abnormal fatty acid metabolism were absent in the spontaneously hypertensive rats carrying numerous nonfunctional mutations in the CD36 gene. Thus, these results suggest that mangiferin treatment mitigates insulin resistance in a rat model of fructose-induced metabolic syndrome by modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle.

Zhou L ，Pan Y ，Chonan R ，Batey R ，Rong X ，Yamahara J ，Wang J ，Li Y ... -  《-》

Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats.

Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid.

Li Y ，Wang J ，Gu T ，Yamahara J ，Li Y ... -  《-》