Potential linkage between dipeptidyl peptidase‐4 inhibitor use and the risk of pancreatitis/pancreatic cancer

Shirakawa, Jun; Terauchi, Yasuo

doi:10.1111/jdi.13192

Cited by 7 publications

(6 citation statements)

References 11 publications

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“…diabetic retinopathy, cardiomyopathy, nephropathy and neuropathy and ‘other diabetic complications. From this specific diabetic complications Venn analysis, a cluster of 23 proteins were identified as common (Fig-7B) and included several important markers such as TNFα, TLR4, CCL2, SOD1, TGFβ1 and SOD2, all of which are deregulated and involved in various stages of diabetic pathogenesis [25],[30,31]. The proteins present in each category and Venn diagram overlaps are listed in Supplementary Data 4.…”

Section: Resultsmentioning

confidence: 99%

“…DPP4 has gained importance as a key therapeutic target over the last few years due to its primary role in increasing endogenous GLP-1 levels, which is found to be important for improved glycemic control and systemic glucose homeostasis. Though there are several approved DPP4 inhibitors, they are relatively expensive and are associated with some side effects such as pancreatitis, joint pain and a possible increased risk of cancer (Mohanty et al, 2019;Kalhotra et al, 2018;Hermansyah et al, 2021;Shirakawa and Terauchi, 2020). Hence there is an increasing interest in identifying new compounds that are cheap, safe and The present study is an attempt to provide transdisciplinary understanding for the antidiabetic action of a clinically established formulation called NK with a special focus on DPP4 inhibition activity.…”

Section: Discussionmentioning

confidence: 99%

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In vitroandin silicoanalysis proving DPP4 inhibition and diabetes associated gene network modulation by a polyherbal formulation –Nisakathakadi Kashaya

Thottappillil

Sahoo

Chakraborty

et al. 2022

Preprint

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Frontiers of disease biology started recognizing the importance of systems and network medicine approach for managing chronic disease like diabetes. Polyherbal preparations like Ayurveda formulations are known to exert a multicomponent-multitargeted mode of action that makes them an ideal tool for delineating new biological insights into this systemic mechanism of disease manifestation and management. Additionally, these formulations are rich repository for identifying novel ligands that interact with drug targets having systemic effects. The current study aims at identifying DPP4 inhibitory potential and modulation of diabetes associated gene network by a clinically established Ayurvedic anti-diabetic formulation Nisakathakadi Kashaya (NK) using in vitro and in silico methods. DPP4 inhibitory potential of NK was evaluated by standard enzyme inhibition assay. Bioinformatics and computational biology tools were used to identify the potential bioactives responsible for the DPP4 inhibitory activity of NK. Molecular docking and dynamics studies of the identified compounds provided insights about the molecular interactions involved in DPP4 inhibition. Target mapping of phytochemicals using network pharmacology tools viz. STITCH, CHEMBL and BindingDB databases was used to depict the multi-targeted interaction of the formulation and a sub network for diabetes related genes and their relationship with other diabetes associated comorbidities were depicted with the help of EnrichR. NK demonstrated a dose dependent DPP4 inhibition with an IC50 of 2.06 μg GAE/mL. Further, the in silico studies identified three compounds namely Terchebin, Locaracemoside B and 1,2,4,6 Tetra o Galloyl Beta D Glucose showing stable interactions with DPP4 when compared to the standard drug Vildagliptin. Network pharmacology studies with the phytochemicals identified from NK revealed a number of genes like TNF, TGFβ, SOD1, SOD2, AKT1, DPP4 and GLP1R in its protein-protein interaction network which are vital to diabetic progression and complications. This suggests that a polyherbal formulation like NK can exert its action through various phytomolecules present. The present work demonstrated that the polyherbal formulation NK has DPP4 inhibition potential and modulates a large number of diabetes related genes and pathways. The approach adopted in the current study by combining in vitro and in silico methods allowed us to understand the mechanism of DPP4 inhibition by the formulation and also the possible pharmacological networking through which the formulation modulate diverse disease related targets.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In vitroandin silicoanalysis proving DPP4 inhibition and diabetes associated gene network modulation by a polyherbal formulation –Nisakathakadi Kashaya

Thottappillil

Sahoo

Chakraborty

et al. 2022

Preprint

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“…These inhibitors have certain advantages as oral hypoglycemic agents, such as weight neutrality, less risk of hypoglycemia, and an insulin-independent mechanism of action as an oral hypoglycemic agent, when compared with other drugs, such as sulfonylureas [ 49 ]. Although DPP-IVis have good therapeutic efficacy and are safe and effective in most patients with T2DM, uncertainties remain regarding the effects of DPP-IV inhibitors on cardiovascular disease, pancreatitis, and other issues [ 50 ]. Compared with synthetic drugs, the search for functional foods with natural and minimal side effects has become a hot research topic.…”

Section: Discussionmentioning

confidence: 99%

Identification of the DPP-IV Inhibitory Peptides from Donkey Blood and Regulatory Effect on the Gut Microbiota of Type 2 Diabetic Mice

Liú

Huang

et al. 2022

Foods

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After being treated with protease K, peptides extracted from donkey blood were separated, identified, and characterized. The results showed that Sephadex G-25 medium purified with MW < 3 kDa had the highest dipeptidyl peptidase IV (DPP-IV) inhibition capacity. Three-hundred-and-thirty-four peptides were identified with UPLC–MS/MS. Peptide Ranker and molecular docking analysis were used to screen active peptides, and 16 peptides were finalized out of the 334. The results showed that the lowest binding energy between P7(YPWTQ) and DPP-IV was −9.1, and the second-lowest binding energy between P1(VDPENFRLL) and DPP-IV was −8.7. The active peptides(MW < 3 kDa) could cause a reduction in the fasting blood glucose levels of type 2 diabetic mice, improve glucose tolerance, and facilitate healing of the damaged structure of diabetic murine liver and pancreas. Meanwhile, the peptides were found to ameliorate the diabetic murine intestinal micro-ecological environment to a certain extent.

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“…Compared to conventional hypoglycemic agents, DPP‐4 inhibitors have a good safety and tolerability profile with no increased risk of hypoglycemia and low gastrointestinal reactions 66–68 . However, a meta‐study showed that patients using DPP‐4 inhibitors had a significantly increased risk of acute pancreatitis 69 . In addition, some studies have shown that DPP‐4 inhibitors can affect the degradation of bradykinin, leading to increased vascular permeability and edema 70 …”

Section: Recent Advances In Treatment Researchmentioning

confidence: 99%

Progress in the treatment of diabetic cardiomyopathy, a systematic review

Shou,

Li,

Fang

et al. 2024

Pharmacology Res & Perspec

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Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis. Ultimately, this can progress to the development of heart failure, arrhythmias, and cardiogenic shock, with severe cases even resulting in sudden cardiac death. Despite several decades of both fundamental and clinical research conducted globally, there are currently no specific targeted therapies available for DCM in clinical practice, and the incidence and mortality rates of heart failure remain persistently high. Thus, this article provides an overview of the current treatment modalities and novel techniques pertaining to DCM, aiming to offer valuable insights and support to researchers dedicated to investigating this complex condition.

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Potential linkage between dipeptidyl peptidase‐4 inhibitor use and the risk of pancreatitis/pancreatic cancer

Cited by 7 publications

References 11 publications

In vitroandin silicoanalysis proving DPP4 inhibition and diabetes associated gene network modulation by a polyherbal formulation –Nisakathakadi Kashaya

In vitroandin silicoanalysis proving DPP4 inhibition and diabetes associated gene network modulation by a polyherbal formulation –Nisakathakadi Kashaya

Identification of the DPP-IV Inhibitory Peptides from Donkey Blood and Regulatory Effect on the Gut Microbiota of Type 2 Diabetic Mice

Progress in the treatment of diabetic cardiomyopathy, a systematic review

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