Abstract
Diabetes is one of the most serious chronic diseases. Numerous drugs including oral agents and traditional Chinese medicines, such as sitagliptin phosphate (SP) and Fuzhujiangtang granules (FJG), have been discovered to treat diabetes and used in combination in clinical practice. However, the exact effect and underlying mechanism of using combined medicine is not clear. In this study, we compared the antidiabetic effect of SP, FJG, and SP plus FJG (SP-FJG) using forty 8-week-old Zucker diabetic fatty (ZDF) rats and 10 age-matched Zucker lean rats as the normal control group. ZDF rats were treated with different therapies, respectively, for 6 weeks. The study showed that the fast blood glucose, random blood glucose (RBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), homeostasis model of assessment-insulin resistance index, triglyceride (TC), superoxide dismutase, and malondialdehyde of each treatment group were improved when compared with the diabetes mellitus (DM) control group. Using SP-FJG in combination had better improvements in OGTT, fast serum insulin levels, TNF-α, and IL-6 compared with using SP individually. Besides, the increased LDL and TC caused by using SP was attenuated by using FJG in combination. Meanwhile, compared with the DM group, 1781 differentially expressed genes (DEGs) (including 1248 mRNA, 211 ncRNA, 202 cirRNA, and 120 miRNA) were enriched in 58 pathways. Through analysis of ceRNA networks, we found that rno-miR-326-3p, rno-miR-423-5p, rno-miR-15b-5p, rno-let-7c-5p, and rno-let-7b-5p were related to pharmacodynamics in different groups. By analyzing the protein-protein interaction (PPI) and coexpression networks of the transcriptomes of different groups, it is inferred that Lrrk2 and Irak3 may be pharmacodynamic genes for type 2 diabetes mellitus (T2DM). Our research compared the treatment of SP, FJG, and SP-FJG and acquainted the PPI network, coexpression network, mutations, and pharmacodynamics genes, which reveals the new mechanisms of pathogenesis of T2DM.
Highlights
IntroductionThe prevalence of chronic noncommunicable diseases is growing at a phenomenal rate [1]
Worldwide, the prevalence of chronic noncommunicable diseases is growing at a phenomenal rate [1]
The sitagliptin phosphate (SP group) and combined medication (SP-Fuzhujiangtang granules (FJG) group) had significant effect of reducing FBG, and the effect of combined medication on reducing random blood glucose (RBG) was better than monotherapy (Table 1)
Summary
The prevalence of chronic noncommunicable diseases is growing at a phenomenal rate [1]. Roughout the world, the number of people with diabetes is estimated to increase from 171 million in 2000 to 366 million by 2030. A growing number of people get diabetes as a result of population growth, aging, urbanization, and increasing prevalence of obesity and lack of exercises [2]. Some oral agents such as sulfonylureas, metformin, sitagliptin phosphate (SP), and injection of insulin are extensively used in the treatment of type 2 diabetes mellitus (T2DM). In the United States, five classes of oral agents (sulfonylureas, metformin, acarbose, troglitazone, and repaglinide) with different mechanism of action are currently available to improve glycemic control in patients with T2DM [4]. The GCTOF/MS analysis and sequencing technology were used to study the therapeutic action of MDG-1, a water-soluble β-d-fructan polysaccharide from O. japonicus [10], and Tangnaikang [11] in T2DM
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