Abstract
We have previously reported that Agriophyllum oligosaccharides (AOS) significantly enhance glycemic control by increasing the activation of insulin receptor (INS-R), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), peroxisome proliferator-activated receptor (PPAR)-γ, and glucose transporter 4 (Glut4) proteins in hepatic tissues. However, the effect of glucose control by AOS on the regulation of pancreatic tissues in db/db mice and MIN6 cells remains to be determined. An oral dose of AOS (380 or 750 mg/kg) was administered to type-2 diabetic db/db mice for 8 weeks to determine whether AOS regulates glucose by the INS-R/IRS/Glut4-mediated insulin pathway. Meanwhile, the effects of AOS on glucose uptake and its related signaling pathway in MIN6 cells were also investigated. The results showed that the random blood glucose (RBG) level in the AOS-treated group was lower than that in the control group. AOS reduced the levels of glycated hemoglobin (HbA1c) and free fatty acid (FFA) and significantly improved the pathological changes in the pancreatic tissues in db/db mice. Moreover, immunohistochemical analysis revealed that the expression of INS-R, IRS-1, IRS-2, and Glut4 was increased in the AOS-treated group than in the model group. Further, in vitro experiments using MIN6 cells showed that AOS regulated INS-R, IRS-1, IRS-2, and Glut4 protein and mRNA levels and attenuated insulin resistance and cell apoptosis. The results of both in vitro and in vivo experiments were comparable. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometric analysis of AOS with precolumn derivatization with 3-amino-9-ethylcarbazole (AEC) tentatively identified five types of sugars: glucose, lactose, rutinose, glucuronic acid, and maltotriose. Our present study clearly showed that AOS is efficacious in preventing hyperglycemia, possibly by increasing insulin sensitivity and improving IR by regulating the INS-R/IRS/Glut4 insulin signal pathway. Therefore, AOS may be considered as a potential drug for diabetes treatment.
Highlights
Diabetes mellitus (DM), characterized by hyperglycemia, is the most common chronic metabolic disorder globally (Kim et al, 2020)
Compared with the high glucose-treated group, we found that Agriophyllum oligosaccharides (AOS) did not significantly reduce the Insulin receptor substrate (IRS)-1 and glucose transporter 4 (Glut4) mRNA levels (Figure 7F,I)
We reported that AOS treatment significantly improved glucose metabolism in db/db mice and high glucoseexposed MIN6 cells
Summary
Diabetes mellitus (DM), characterized by hyperglycemia, is the most common chronic metabolic disorder globally (Kim et al, 2020). The number of people with DM and its complications is increasing globally (Vieira et al, 2019). IR is the main driver of T2DM and causes DM-related complications (Wang et al, 2019a; Gao et al, 2019). To control T2DM, developing safe, effective, and low-toxicity drugs that ameliorate IR is important. A previous report showed that synthetic drugs are associated with side effects (Wang et al, 2019b). Around 20–30% of patients receiving metformin tend to develop loss of appetite, nausea, vomiting, abdominal pain, acid reflux, and other gastrointestinal side effects, whereas some others develop lactic acidosis (Dujic et al, 2016). A previous clinical study has reported that the incidence of lactic acidosis is very low in patients with T2DM receiving metformin (DeFronzo et al, 2016). Identifying novel herbal agents with fewer side effects for treating T2DM is imperative
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
