Phytochemicals as Potential Epidrugs in Type 2 Diabetes Mellitus

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.

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APOPTOTIC PROCESSES’ RESEARCH ON THE MODEL OF TYPE 2 DIABETES MELLITUS ON OBESITY’S BACKGROUND UNDER THE INFLUENCE OF DENSE BEAN EXTRACT

Wiadomości Lekarskie ◽

10.36740/wlek202008119 ◽

2020 ◽

Vol 73 (8) ◽

pp. 1690-1695

Author(s):

Viktoria A. Rybak ◽

Viktoria V. Korol ◽

Natalia V. Derkach

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cell Function ◽

Male Rats ◽

Control Group ◽

Citrate Buffer ◽

Pancreatic Cell ◽

Alcoholic Fatty Liver

The aim of the study was to observe the influence of dense bean extract on the intensity of apoptotic processes in the liver cells and pancreas of rats on a model of type 2 diabetes mellitus on obesity’s background. Materials and methods: The main method was to model type 2 diabetes mellitus on the background of obesity in organism of mature six-month-old male rats of the Wistar population (n = 21), weighing 150-170 g. The modelling was carried out by intraperitoneal low dose administration of streptozotocin (30 mg / kg, in citrate buffer pH = 4, 5) inside after three months period of keeping animals on a combined diet. Apoptosis in DNA samples of liver and pancreas cells was identified in duplicates using electrophoresis in a 1% agarose gel with using a 1kb DNA SibEnzyme apoptosis marker (from 10,000 to 250 nucleotides). Results: Only in two of the seven studied DNA samples of the pancreas of a group of rats, treated with a dense bean extract, were observed the traces of necrosis without detectable manifestations of the apoptotic process. It situates at the level of indicators of the animals’ intact control group and indicates the distinct effect’s presence which includes maintaining pancreas cells survival (in both endocrine and exocrine parts) if imbalance of carbohydrate and lipid metabolism take place in organism. Conclusion: Dense bean extract showed a more distinct effect than the comparison drug metformin in relation to the risk of premature loss of pancreatic cell function and the development of non-alcoholic fatty liver disease. A dense bean extract is promising for further pharmacological studies, with the aim of creating phytopreparations – «Glyphasonorm» tablets and «Glyfasolin» capsules for the correction of type 2 diabetes mellitus and its complications.

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The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus

Frontiers in Pharmacology ◽

10.3389/fphar.2020.585487 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ya-yi Jiang ◽

Jia-cheng Shui ◽

Bo-xun Zhang ◽

Jia-wei Chin ◽

Ren-song Yue

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cell Function ◽

Public Health Problem ◽

Therapeutic Effects ◽

Global Public Health

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a global public health problem. Studies on T2DM prevention and treatment mostly focus on discovering therapeutic drugs. Artemisinin and its derivatives were originally used as antimalarial treatments. In recent years, the roles of artemisinins in T2DM have attracted much attention. Artemisinin treatments not only attenuate insulin resistance and restore islet ß-cell function in T2DM but also have potential therapeutic effects on diabetic complications, including diabetic kidney disease, cognitive impairment, diabetic retinopathy, and diabetic cardiovascular disease. Many in vitro and in vivo experiments have confirmed the therapeutic utility of artemisinin and its derivatives on T2DM, but no article has systematically demonstrated the specific role artemisinin plays in the treatment of T2DM. This review summarizes the potential therapeutic effects and mechanism of artemisinin and its derivatives in T2DM and associated complications, providing a reference for subsequent related research.

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Mechanisms and Characteristics of Sulfonylureas and Glinides

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666191224141617 ◽

2020 ◽

Vol 20 (1) ◽

pp. 37-56 ◽

Cited By ~ 3

Author(s):

Wei Lv ◽

Xianqing Wang ◽

Qian Xu ◽

Wencong Lu

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cell Function ◽

Medical Profession ◽

Pancreatic Cell ◽

Peripheral Tissues ◽

Depth Study ◽

Oral Hypoglycemic Drugs

Background: Type 2 diabetes mellitus is a complex progressive endocrine disease characterized by hyperglycemia and life-threatening complications. It is the most common disorder of pancreatic cell function that causes insulin deficiency. Sulfonylurea is a class of oral hypoglycemic drugs. Over the past half century, these drugs, together with the subsequent non-sulfonylureas (glinides), have been the main oral drugs for insulin secretion. Objective: Through in-depth study, the medical profession considers it as an important drug for improving blood sugar control. Methods: The mechanism, characteristics, efficacy and side effects of sulfonylureas and glinides were reviewed in detail. Result: Sulfonylureas and glinides not only stimulated the release of insulin from pancreatic cells, but also had many extrapanular hypoglycemic effect, such as reducing the clearance rate of insulin in liver, reducing the secretion of glucagon, and enhancing the sensitivity of peripheral tissues to insulin in type 2 diabetes mellitus. Conclusion: Sulfonylureas and glinides are effective first-line drugs for the treatment of diabetes mellitus. Although they have the risk of hypoglycemia, weight gain and cardiovascular disease, their clinical practicability and safety can be guaranteed as long as they are reasonably used.

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Plasma relaxin concentration is related to beta-cell function and insulin sensitivity in women with type 2 diabetes mellitus

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2007.10.017 ◽

2008 ◽

Vol 79 (3) ◽

pp. e1-e3 ◽

Cited By ~ 13

Author(s):

Barbara Szepietowska ◽

Maria Gorska ◽

Malgorzata Szelachowska

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Sensitivity ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function

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In Vitro effect of DDE exposure on the regulation of lipid metabolism and secretion in McA-RH7777 hepatocytes: A potential role in dyslipidemia which may increase the risk of type 2 diabetes mellitus

Toxicology in Vitro ◽

10.1016/j.tiv.2016.08.011 ◽

2016 ◽

Vol 37 ◽

pp. 9-14 ◽

Cited By ~ 9

Author(s):

Antonio B. Ward ◽

Mary B. Dail ◽

Janice E. Chambers

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Lipid Metabolism ◽

Potential Role ◽

Vitro Effect

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Teucrium polium: Potential Drug Source for Type 2 Diabetes Mellitus

Biology ◽

10.3390/biology11010128 ◽

2022 ◽

Vol 11 (1) ◽

pp. 128

Author(s):

Yaser Albadr ◽

Andrew Crowe ◽

Rima Caccetta

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Secretion ◽

Β Cells ◽

Pancreatic Β Cells ◽

Glucose Levels ◽

Teucrium Polium

The prevalence of type 2 diabetes mellitus is rising globally and this disease is proposed to be the next pandemic after COVID-19. Although the cause of type 2 diabetes mellitus is unknown, it is believed to involve a complex array of genetic defects that affect metabolic pathways which eventually lead to hyperglycaemia. This hyperglycaemia arises from an inability of the insulin-sensitive cells to sufficiently respond to the secreted insulin, which eventually results in the inadequate secretion of insulin from pancreatic β-cells. Several treatments, utilising a variety of mechanisms, are available for type 2 diabetes mellitus. However, more medications are needed to assist with the optimal management of the different stages of the disease in patients of varying ages with the diverse combinations of other medications co-administered. Throughout modern history, some lead constituents from ancient medicinal plants have been investigated extensively and helped in developing synthetic antidiabetic drugs, such as metformin. Teucrium polium L. (Tp) is a herb that has a folk reputation for its antidiabetic potential. Previous studies indicate that Tp extracts significantly decrease blood glucose levels r and induce insulin secretion from pancreatic β-cells in vitro. Nonetheless, the constituent/s responsible for this action have not yet been elucidated. The effects appear to be, at least in part, attributable to the presence of selected flavonoids (apigenin, quercetin, and rutin). This review aims to examine the reported glucose-lowering effect of the herb, with a keen focus on insulin secretion, specifically related to type 2 diabetes mellitus. An analysis of the contribution of the key constituent flavonoids of Tp extracts will also be discussed.

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Inflammation of adipose tissue. Part 2. Pathogenetic role in type 2 diabetes mellitus

Problems of Endocrinology ◽

10.14341/probl200955543-48 ◽

2009 ◽

Vol 55 (5) ◽

pp. 43-48 ◽

Cited By ~ 3

Author(s):

V Shvarts

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Adipose Tissue ◽

Cell Function ◽

Signal Pathway ◽

Insulin Signal ◽

Kinase Cascade

This review deals with the role of adipose tissue inflammation (ATI) in the development of type 2 diabetes mellitus (DM2). ATI is regarded as a link between obesity and DM2. The review illustrates the involvement of main adipokines in pathogenesis of DM2 and provides a detailed description of such factors as impaired adiponectin and stimulation of cytokine production responsible for metabolic disorders, activation of lipolysis, in adipocytes, increased fatty acid and triglyceride levels, suppression of insulin activity at the receptor and intracellular levels. Adipokines, in the first place cytokines, act on the insulin signal pathway and affect the intracellular inflammatory kinase cascade. At the intercellular level, ATI stimulates JNK and IKK-beta/kB responsible for the development of insulin resistance via such mechanisms as activation of cytokine secretion in the adipose tissue, oxidative stress, and induction of endoplasmic reticulum enzymes. The key role of JNK and IKK-beta/kB in the inhibition of the insulin signal pathway is mediated through inactivation of insulin receptor substrate 1. Also, it is shown that ATI modulates B-cell function and promotes progressive reduction of insulin secretion.

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1α,25-dihydroxyvitamin D3 promotes osseointegration of titanium implant via downregulating AGEs/RAGE pathway in T2DM

Endocrine Connections ◽

10.1530/ec-18-0241 ◽

2018 ◽

Vol 7 (11) ◽

pp. 1186-1195 ◽

Cited By ~ 1

Author(s):

Tingting Jia ◽

Ya-nan Wang ◽

Dongjiao Zhang ◽

Xin Xu

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Bone Microarchitecture ◽

Titanium Implant ◽

Underlying Mechanism ◽

High Rate ◽

Alizarin Red

Diabetes-induced advanced glycation end products (AGEs) overproduction would result in compromised osseointegration of titanium implant and high rate of implantation failure. 1α,25-dihydroxyvitamin D3 (1,25VD3) plays a vital role in osteogenesis, whereas its effects on the osseointegration and the underlying mechanism are unclear. The purpose of this study was to investigate that 1,25VD3 might promote the defensive ability of osseointegration through suppressing AGEs/RAGE in type 2 diabetes mellitus. In animal study, streptozotocin-induced diabetic rats accepted implant surgery, with or without 1,25VD3 intervention for 12 weeks. After killing, the serum AGEs level, bone microarchitecture and biomechanical index of rats were measured systematically. In vitro study, osteoblasts differentiation capacity was analyzed by alizarin red staining, alkaline phosphatase assay and Western blotting, after treatment with BSA, AGEs, AGEs with RAGE inhibitor and AGEs with 1,25VD3. And the expression of RAGE protein was detected to explore the mechanism. Results showed that 1,25VD3 could reverse the impaired osseointegration and mechanical strength, which possibly resulted from the increased AGEs. Moreover, 1,25VD3 could ameliorate AGEs-induced damage of cell osteogenic differentiation, as well as downregulating the RAGE expression. These data may provide a theoretical basis that 1,25VD3 could work as an adjuvant treatment against poor osseointegration in patients with type 2 diabetes mellitus.

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