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Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus.

ABSTRACT: Type 2 diabetes Mellitus (T2DM) prevalence has significantly increased worldwide in recent years due to population age, obesity, and modern sedentary lifestyles. The projections estimate that 439 million people will be diabetic in 2030. T2DM is characterized by an impaired β-pancreatic cell function and insulin secretion, hyperglycemia and insulin resistance, and recently the epigenetic regulation of β-pancreatic cells differentiation has been underlined as being involved. It is currently known that several bioactive molecules, widely abundant in plants used as food or infusions, have a key role in histone modification and DNA methylation, and constituted potential epidrugs candidates against T2DM. In this sense, in this review the epigenetic mechanisms involved in T2DM and protein targets are reviewed, with special focus in studies addressing the potential use of phytochemicals as epidrugs that prevent and/or control T2DM in vivo and in vitro. As main findings, and although some controversial results have been found, bioactive molecules with epigenetic regulatory function, appear to be a potential replacement/complementary therapy of pharmacological hypoglycemic drugs, with minimal side effects. Indeed, natural epidrugs have shown to prevent or delay the T2DM development and the morbidity associated to dysfunction of blood vessels, eyes and kidneys due to sustained hyperglycemia in T2DM patients.

SUBMITTER: Ramirez-Alarcon K

PROVIDER: S-EPMC8204854 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Type 2 diabetes mellitus (T2DM) is a multifactorial and multigenetic disease, and its pathogenesis is complex and largely unknown. In the present study, microarray data (GSE201966) of β‑cell enriched tissue obtained by laser capture microdissection were downloaded, including 10 control and 10 type 2 diabetic subjects. A comprehensive bioinformatics analysis of microarray data in the context of protein‑protein interaction (PPI) networks was employed, combined with subcellular location information to mine the potential candidate genes for T2DM and provide further insight on the possible mechanisms involved. First, differential analysis screened 108 differentially expressed genes. Then, 83 candidate genes were identified in the layered network in the context of PPI via network analysis, which were either directly or indirectly linked to T2DM. Of those genes obtained through literature retrieval analysis, 27 of 83 were involved with the development of T2DM; however, the rest of the 56 genes need to be verified by experiments. The functional analysis of candidate genes involved in a number of biological activities, demonstrated that 46 upregulated candidate genes were involved in 'inflammatory response' and 'lipid metabolic process', and 37 downregulated candidate genes were involved in 'positive regulation of cell death' and 'positive regulation of cell proliferation'. These candidate genes were also involved in different signaling pathways associated with 'PI3K/Akt signaling pathway', 'Rap1 signaling pathway', 'Ras signaling pathway' and 'MAPK signaling pathway', which are highly associated with the development of T2DM. Furthermore, a microRNA (miR)‑target gene regulatory network and a transcription factor‑target gene regulatory network were constructed based on miRNet and NetworkAnalyst databases, respectively. Notably, hsa‑miR‑192‑5p, hsa‑miR‑124‑5p and hsa‑miR‑335‑5p appeared to be involved in T2DM by potentially regulating the expression of various candidate genes, including procollagen C‑endopeptidase enhancer 2, connective tissue growth factor and family with sequence similarity 105, member A, protein phosphatase 1 regulatory inhibitor subunit 1 A and C‑C motif chemokine receptor 4. Smad5 and Bcl6, as transcription factors, are regulated by ankyrin repeat domain 23 and transmembrane protein 37, respectively, which might also be used in the molecular diagnosis and targeted therapy of T2DM. Taken together, the results of the present study may offer insight for future genomic‑based individualized treatment of T2DM and help determine the underlying molecular mechanisms that lead to T2DM.

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Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus.

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