Dataset Information

Tetradecyl 2,3-Dihydroxybenzoate Improves the Symptoms of Diabetic Mice by Modulation of Insulin and Adiponectin Signaling Pathways.

ABSTRACT: Background: Tetradecyl 2,3-dihydroxybenzoate (ABG-001) derived from Chinese medicine, gentiana regescens Franch is a leading compound with NGF mimic effect, it can induce neurite outgrowth of PC12 cells via the IGF-1/PI3K/ERK signaling pathway. Thus, we inferred that this compound had anti-diabetic effect and used streptozocin (STZ)-induced diabetic mice to indicate it. Methods: ABG-001 was synthesized with 2,3-dihydroxybenzoic acid and tetradecyl alcohol under certain reaction conditions. STZ-induced diabetic mice were used to investigate anti-diabetic effect. Oral glucose tolerance test, insulin tolerance test, RT-PCR, Western blot, ELISA assays and histological section were performed to do the analysis of action mechanism. Results: ABG-001 showed anti-diabetic effect in STZ-induced diabetic mice. In diabetic mice, the anti-diabetic effect of ABG-001 at a dose of 20 mg/kg was equal with metformin at a dose of 140 mg/kg. Moreover, glucose tolerance and insulin sensitivity were significantly improved on diabetic mice. The plasma insulin, adiponectin and leptin were notably increased, whereas glucagon remarkably decreased. The gene expressions of adiponectin and leptin in adipose tissue, glucose transporter 4 and adiponectin receptor 1 in liver and gastrocnemius, ADR2 in hypothalamus and pancreas were obviously increased. Conclusion: ABG-001 exerts antidiabetic effects via modulation of insulin and adiponectin signaling pathways. This new type of molecule could be a promising drug candidate for treatment of diabetes.

SUBMITTER: Xiang L

PROVIDER: S-EPMC5693855 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Tetradecyl 2,3-Dihydroxybenzoate Improves the Symptoms of Diabetic Mice by Modulation of Insulin and Adiponectin Signaling Pathways.

Xiang Lan L Li Jing J Wang Yanhui Y Tang Ruiqi R Wang Qian Q Wu Qiaobei Q Qi Jianhua J

Frontiers in pharmacology 20171113

Background: Tetradecyl 2,3-dihydroxybenzoate (ABG-001) derived from Chinese medicine, gentiana regescens Franch is a leading compound with NGF mimic effect, it can induce neurite outgrowth of PC12 cells via the IGF-1/PI3K/ERK signaling pathway. Thus, we inferred that this compound had anti-diabetic effect and used streptozocin (STZ)-induced diabetic mice to indicate it. Methods: ABG-001 was synthesized with 2,3-dihydroxybenzoic acid and tetradecyl alcohol under certain react ...[more]

PMID: 29180962

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Project description:: Silk fibroin hydrolysates have been reported to reduce hyperglycemia, but the mechanism has not been determined in Asian type 2 diabetes (T2DM). We hypothesized that the consumption of acid hydrolyzed silk peptides (SPs) alleviates hyperglycemia by improving insulin sensitivity and subsequently normalizing glucose-stimulated insulin secretion in T2DM. We investigated this hypothesis in a partial pancreatectomized (Px) rat model. Px rats was assigned randomly to the following six groups and fed assigned diet for 8 weeks: the Px-CON (0.5 g/kg/day dextrin), the SP-L (0.05 g/kg/day), the SP-M (0.1 g/kg/day), the SP-H (0.5 g/kg/day), the positive-CON (30 mg/kg/day metformin), or the normal-CON (sham-operated rats; 0.5 g/kg/day dextrin). SPs contained high levels of glycine, alanine, and serine. We found SPs dose-dependently increased food efficiency and body weight gain in Px rats. Animals in the Px-control group rats exhibited lower glucose metabolism, as evidenced by impaired glucose-stimulated insulin secretion coupled with impaired insulin sensitivity, and reduced bone mineral density (BMD) and lean body mass (LBM), compared to normal-CON. SPs and metformin similarly partially protected against Px-induced BMD loss in the lumbar spine and femur. Px-induced decreases in LBM were dose-dependently prevented by SPs, and muscle forces in the SP-M and SP-H groups were maintained at the normal-CON level. Glucose tolerance was dose-dependently improved by SPs as determined by oral glucose tolerance and oral maltose tolerance tests, and glucose tolerances were similar in the SP-H and positive-CON groups. Insulin tolerance, an index of insulin sensitivity, was dose-dependently enhanced by SPs, and the SP-H group exhibited better insulin tolerance than the positive-CON group as determined by intraperitoneal insulin sensitivity testing. Insulin secretory capacity assessed using a hyperglycemic clamp improved in the following order: Px-control <SA-L <SA-M <positive-control <SA-H <normal-control. SP-M prevented gut microbiota dysbiosis. In conclusion, SPs administered at 0.1-0.5 g/kg/day improved glucose regulation by potentiating both insulin secretion and insulin sensitivity in non-obese T2DM rats.

Dataset Information

Tetradecyl 2,3-Dihydroxybenzoate Improves the Symptoms of Diabetic Mice by Modulation of Insulin and Adiponectin Signaling Pathways.

Publications

Tetradecyl 2,3-Dihydroxybenzoate Improves the Symptoms of Diabetic Mice by Modulation of Insulin and Adiponectin Signaling Pathways.

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