Chicory inulin ameliorates type 2 diabetes mellitus and suppresses JNK and MAPK pathways in vivo and in vitro

2017 ◽  
Vol 61 (8) ◽  
pp. 1600673 ◽  
Author(s):  
Chong Ning ◽  
Xiyao Wang ◽  
Song Gao ◽  
Jingjing Mu ◽  
Yuehua Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mapk Pathways ◽  
Chicory Inulin

Animal Research for Type 2 Diabetes Mellitus, Its Limited Translation for Clinical Benefit, and the Way Forward

2018 ◽  
Vol 46 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Zeeshan Ali ◽  
P. Charukeshi Chandrasekera ◽  
John J. Pippin
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Animal Models ◽  
Animal Research ◽  
Therapeutic Options ◽  
Research Findings

Obesity and type 2 diabetes mellitus (T2DM) have reached pandemic proportions worldwide, and considerable research efforts have been dedicated to investigating disease pathology and therapeutic options. The two hallmark features of T2DM, insulin resistance and pancreatic dysfunction, have been studied extensively by using various animal models. Despite the knowledge acquired from such models, particularly mechanistic discoveries that sometimes mimic human T2DM mechanisms or pathways, many details of human T2DM pathogenesis remain unknown, therapeutic options remain limited, and a cure has eluded research. Emerging human data have raised concern regarding inter-species differences at many levels (e.g. in gene regulation, pancreatic cytoarchitecture, glucose transport, and insulin secretion regulation), and the subsequent impact of these differences on the clinical translation of animal research findings. Therefore, it is important to recognise and address the translational gap between basic animal-based research and the clinical advances needed to prevent and treat T2DM. The purpose of this report is to identify some limitations of T2DM animal research, and to propose how greater human relevance and applicability of hypothesis-driven basic T2DM research could be achieved through the use of human-based data acquisition at various biological levels. This report addresses how in vitro, in vivo and in silico technologies could be used to investigate particular aspects of human glucose regulation. We do not propose that T2DM animal research has been without value in the identification of mechanisms, pathways, or potential targets for therapies, nor do we claim that human-based methods can provide all the answers. We recognise that the ultimate goal of T2DM animal research is to identify ways to advance the prevention, recognition and treatment of T2DM in humans, but postulate that this is where the use of animal models falls short, despite decades of effort. The best way to achieve this goal is by prioritising human-centred research.

scholarly journals Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (6) ◽  
pp. 1517 ◽  
Author(s):  
Kai Wang ◽  
Yu Su ◽  
Yuting Liang ◽  
Yanhui Song ◽  
Liping Wang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Enzymatic Activity ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

In vitro (α-Glucosidase and α-Amylase Inhibition) and in vivo Antidiabetic Property of Phytic Acid (IP6) in Streptozotocin-Nicotinamide-Induced Type 2 Diabetes Mellitus (NIDDM) in Rats

2011 ◽  
Vol 8 (1) ◽  
Author(s):  
Asokkumar Kuppusamy ◽  
Umamaheswari Muthusamy ◽  
Sivashanmugam Andichetiar Thirumalaisamy ◽  
Subhadradevi Varadharajan ◽  
Kalyanasubramaniam Ramasamy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Phytic Acid

scholarly journals Free Radicals Scavenging Capacity, Antidiabetic and Antihypertensive Activities of Flavonoid-Rich Fractions from Leaves ofTrichilia emeticaandOpilia amentaceain an Animal Model of Type 2 Diabetes Mellitus

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Kiessoun Konaté ◽  
Kassi Yomalan ◽  
Oksana Sytar ◽  
Patrice Zerbo ◽  
Marian Brestic ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Animal Model ◽  
Type 2 Diabetes Mellitus ◽  
Therapeutic Potential ◽  
Radical Scavenging Activity ◽  
Radical Scavenging

Trichilia emeticaandOpilia amentaceatraditional Burkinabe medicinal plants were investigated to determine their therapeutic potential to inhibit key enzymes in carbohydrate metabolism, which has relevance to the management of type 2 diabetes.In vitroandin vivoantioxidant and antihypertensive potential and antilipidemia and antihyperglycemia activities in an animal model of type 2 diabetes mellitus have been studied. The antioxidant activity of the flavonoids from leaves ofTrichilia emeticaandOpilia amentaceahas been evaluated usingβ-carotene-linoleic acid system, 1,1-diphenyl-2-picrylhydrazyl inhibitory activity, chelation of iron (II) ions, and lipid peroxidation which showed more pronounced antioxidant capacities ofTrichilia emetica. Total cholesterol concentrations decreased in an animal model of type 2 diabetes mellitus under effects of flavonoid-rich fractions from leaves ofTrichilia emeticaandOpilia amentaceahas been observed. Extract of flavonoid-rich fractions fromTrichilia emeticashown maximum radical scavenging activity and possessed marked antiamylase activity which may be due to the presence of certain secondary metabolites. Suggested better antihyperglycemia, antilipidemia, and antihypertensive properties of flavonoid-rich fractions fromTrichilia emeticacompared to the extract ofOpilia amentaceaare demonstrating antidiabetic potential ofTrichilia emeticaas therapeutic targets for the management of type 2 diabetes.

scholarly journals Intervention of Gastrodin in Type 2 Diabetes Mellitus and Its Mechanism

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Bai ◽  
Ke Mo ◽  
Guirong Wang ◽  
Wanling Chen ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Receptors ◽  
Control Group ◽  
Sensitivity Index

As a severe metabolic disease, type 2 diabetes mellitus (T2DM) has become a serious threat to human health in recent years. Gastrodin, as a primary chemical constituent in Gastrodia elata Blume, has antidiabetic effects. However, the possible mechanisms are unclear. The aim of the present study was to investigate the effects and possible mechanisms of gastrodin on the treatment of T2DM. In vivo, after treatment with gastrodin for 6 weeks, fasting blood glucose levels, blood lipid metabolism, and insulin sensitivity index values were remarkably reduced compared with those of the diabetic control group. The values of aspartate aminotransferase and alanine aminotransferase also showed that gastrodin alleviates liver toxicity caused by diabetes. Moreover, gastrodin relieved pathological damage to the pancreas in T2DM rats. In vitro, gastrodin alleviated insulin resistance by increasing glucose consumption, glucose uptake, and glycogen content in dexamethasone-induced HepG2 cells. The Western blotting results showed that gastrodin upregulated the expression of insulin receptors and ubiquitin-specific protease 4 (USP4) and increased the phosphorylation of GATA binding protein 1 (GATA1) and protein kinase B (AKT) in vivo and in vitro. Furthermore, gastrodin decreased the ubiquitin level of the insulin receptor via UPS4 and increased the binding of GATA1 to the USP4 promoter. Additionally, administration of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway inhibitors MK-2206 and LY294002 abolished the beneficial effects of gastrodin. Our results indicate that gastrodin promotes the phosphorylation of GATA1 via the PI3K/AKT pathway, enhances the transcriptional activity of GATA1, and then increases the expression level of USP4, thereby reducing the ubiquitination and degradation of insulin receptors and ultimately improving insulin resistance. Our study provides scientific evidence for the beneficial actions and underlying mechanism of gastrodin in the treatment of T2DM.

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

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.

scholarly journals Zinc As A Factor Affecting Serum Calcification Propensity in Patients With Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Shinya Nakatani ◽  
Katsuhito Mori ◽  
Mika Sonoda ◽  
Kozo Nishide ◽  
Hideki Uedono ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Serum Zinc ◽  
Zinc Level ◽  
Physiological Concentration ◽  
Cross Sectional

Abstract Background: Zinc inhibits vascular calcification in vivo and in vitro. Patients with type 2 diabetes mellitus show hypozincemia and are at an elevated risk of cardiovascular events. Recently, the in vitro test (T50-test) was developed for the determination of serum calcification propensity. This cross-sectional study investigated the association between serum zinc and T50 in type 2 diabetes mellitus patients and the effect of zinc on T50in vitro.Methods: The subjects were 132 type 2 diabetes mellitus patients with various kidney function. We measured T50 levels by the established nephelometric method.Results: The median (interquartile range) levels of T50 and serum zinc were 306 (269 to 332) min, and 80.0 (70.1 to 89.8) µg/dL, respectively. Serum zinc level was significantly and positively correlated with T50 (rs = 0.219, p = 0.012). This association remained significant in multivariable-adjusted analysis, and was independent of known factors including phosphate, calcium, and magnesium. Renal function and glycemic control were not significantly associated with T50. Finally, addition of physiological concentration of exogenous zinc chloride significantly increased the serum T50 in vitro.Conclusions: This is the first report to investigate the association between serum calcification propensity and zinc levels in type 2 diabetes mellitus patients. Our data suggest that serum zinc is an independent factor that inhibits serum calcification propensity.

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