Trelagliptin succinate: DPP-4 inhibitor to improve insulin resistance in adipocytes

Liu, Zhenhua; Xu, Lanting; Xing, Mingzhao; Xu, Xiaojie; Wei, Jinfeng; Wang, Jinmei

doi:10.1016/j.biopha.2020.109952

Cited by 21 publications

(8 citation statements)

References 31 publications

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“…In a recent study by Liu et al, 25–100 μM Trelagliptin was used to treat mouse 3T3-L1 preadipocytes [ 26 ]. We tested the cytotoxicity of the osteoblastic cell line MC3T3-E1.…”

Section: Resultsmentioning

confidence: 99%

Trelagliptin stimulates osteoblastic differentiation by increasing runt-related transcription factor 2 (RUNX2): a therapeutic implication in osteoporosis

Shao

Cao

et al. 2021

Bioengineered

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Osteoporosis, an aging-associated bone metabolic disease, is affecting millions of people worldwide. The deregulated process of osteoblastic differentiation has been linked with the progression of osteoporosis. Trelagliptin is a long-acting inhibitor of DPP-4 used for the management of type 2 diabetes mellitus. However, it is unknown whether Trelagliptin possesses a beneficial effect in osteoblastic differentiation. Interestingly, we found that treatment with Trelagliptin enhanced differentiation and promoted the mineralization of MC3T3-E1 cells. Firstly, Trelagliptin increased the activity of alkaline phosphatase (ALP) and promoted osteoblastic calcium deposition. Additionally, treatment with Trelagliptin upregulated ALP, osteocalcin (OCN), osteopontin (OPN), and bone morphogenetic protein-2 (BMP-2). Notably, Trelagliptin increased RUNX2, a major regulator of osteoblastic differentiation. Mechanistically, Trelagliptin upregulated the levels of p-AMPKα. Blockage of AMPK with compound C abolished the effects of Trelagliptin in RUNX2 and osteoblastic differentiation, suggesting the involvement of AMPK. Our findings suggest that Trelagliptin might possess a potential for the treatment of osteoporosis.

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“…In a recent study by Liu et al, 25–100 μM Trelagliptin was used to treat mouse 3T3-L1 preadipocytes [ 26 ]. We tested the cytotoxicity of the osteoblastic cell line MC3T3-E1.…”

Section: Resultsmentioning

confidence: 99%

Trelagliptin stimulates osteoblastic differentiation by increasing runt-related transcription factor 2 (RUNX2): a therapeutic implication in osteoporosis

Shao

Cao

et al. 2021

Bioengineered

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“…Furthermore, inhibition of C/EBP-α and PPAR-γ reduces lipid accumulation in WAT and can therefore contribute to obesity prevention. Additionally, it can reduce the risk of diseases such as obesity-induced metabolic syndrome and vascular diseases [ 46 , 47 ]. Therefore, our results suggest that EF-2001 inhibited adipogenesis by reduction of C/EBP-α and PPAR-γ expression and nuclear translocation both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Heat-Killed Enterococcus faecalis Prevents Adipogenesis and High Fat Diet-Induced Obesity by Inhibition of Lipid Accumulation through Inhibiting C/EBP-α and PPAR-γ in the Insulin Signaling Pathway

et al. 2022

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Increasing consumption of food with high caloric density and a sedentary lifestyle have influenced the increasing obesity prevalence worldwide. The recent pandemic has contributed to this problem. Obesity refers to a state in which lipid accumulates excessively in adipocytes and adipose tissues. Dried heat-killed Enterococcus faecalis (EF-2001) prevents allergic mechanisms, inflammation, and tumor progression. In the present study, we investigated the effects of EF-2001 on high fat diet (HFD)-induced obese rats. The degree of obesity in experimental rats was reduced after 6 weeks of oral administration of 3 mg/kg or 30 mg/kg dosages of EF-2001, indicating regulating effects in rats with HFD-induced obesity. We found that EF-2001 decreased the amounts of total cholesterol, triglyceride, and non-high density lipoprotein (HDL) in HFD-induced obese rats. The effects of EF-2001 on 3T3-L1 adipocytes stained with Oil red O stain are shown in reductions of lipid accumulation, respectively. In addition, we examined the relationships between EF-2001 treatment and mechanisms for the insulin signaling of adipogenesis in 3T3-L1 cells. EF-2001 induced down-regulation in phosphorylation of Erk, JNK, and Akt through the inhibition of insulin receptor phosphorylation. EF-2001 inhibits the expressions of C/EBP-α and PPAR-γ, a lipid metabolism-related transcription factor through confocal microscope observation and Western blot on 3T3-L1 adipocytes and HFD-induced obese rats. Based on our results, intake of EF-2001 significantly prevented HFD-induced obesity in rats through inhibition of C/EBP-α and PPAR-γ in the insulin signaling pathway on lipid accumulation.

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“…35 Alike prior studies that manifested that combination treatment of DPP-4 inhibitor was secure and effective, the current survey indicated that the risks of severe hypoglycemia and death in patients dosed roughly with DPP-4 inhibitor in dual therapy were not different from those obtained with proper dosing of DPP-4 inhibitor as monotherapy. 36,37 To achieve much more effective results in controlling fasting and random blood glucose level and glycosylated hemoglobin we used combination therapy (dual therapy). Encouraging results were obtained in the case of dipeptidyl peptidase class along with sulfonylurea which reduces HbA1C concentration up to 2.25 from the results observed at baseline and the present results are in accordance with the observations reported by Amir Q and coworkers(2017).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial

Ms.¹,

Khan²,

Khan³

et al. 2020

JRMC

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Objective: This trial was conducted to evaluate the effectiveness of oral hypoglycemic agents on diabetic control and biochemical parameters of known diabetic subjects. Introduction: T2DM occurs due to abnormal metabolism of carbohydrate, proteins and lipids leading to increased blood glucose characterized by polyuria and polydypsia due to relative 5deficiency or lack of insulin. Beside dietary control and insulin therapy, various oral hypoglycemic such as sulfonylurea biguanide, thiazolidinedione, DPP–4 inhibitors, glucagon–like peptide inhibitors and SGL2. Material and Methods: This comparative trial was carried out on previously diagnosed type–2 diabetic subjects. This trial was conducted at health care centers of District Nowshehra viz. NMC Nowshehra, DHQ Hospital Nowshehra, and ICS, Peshawar in collaboration with KMC and PIMC Peshawar, Khyber Pakhtunkhwa, Pakistan. A total of 200 known diabetic subjects were randomly recruited on the basis of predetermined selection criteria and were splited into two groups. Group A having 100 diabetic subjects was given DPP–4 inhibitor; Sitagliptin 50 mg two times a day alone for six (06) months while Group B comprising of 100 patients were treated with combination of DPP–4 inhibitor (Sitagliptin 50 mg 1BD) and Metformin in a dose of 500 mg two times a day. Venous blood samples were taken from each patient in both fasting (10–12 hour night long fast) and random (2 hour post prandial) state. FBS, RBS, HbA1C, S. creatinine and fasting S. lipid profile were determined by using spectrophotometric colorimetric methods using kits (procured from Elitech, Spain) at 03 and 06 months follow up. Inclusion criteria was subjects with T2DM of age 18 years and above. T2DM patients on insulin, diabetic nephropathy and retinopathy were excluded. The data was analyzed by using SPSS software version 20. Results: Significant results (p < 0.05) were seen for glycemic control (FBS, RBS, HbA1C) in Group B as compare to Group A patients.

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Trelagliptin succinate: DPP-4 inhibitor to improve insulin resistance in adipocytes

Cited by 21 publications

References 31 publications

Trelagliptin stimulates osteoblastic differentiation by increasing runt-related transcription factor 2 (RUNX2): a therapeutic implication in osteoporosis

Trelagliptin stimulates osteoblastic differentiation by increasing runt-related transcription factor 2 (RUNX2): a therapeutic implication in osteoporosis

Heat-Killed Enterococcus faecalis Prevents Adipogenesis and High Fat Diet-Induced Obesity by Inhibition of Lipid Accumulation through Inhibiting C/EBP-α and PPAR-γ in the Insulin Signaling Pathway

Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial

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