scholarly journals Wushenziye Formula Inhibits Pancreatic β Cell Apoptosis in Type 2 Diabetes Mellitus via MEK-ERK-Caspase-3 Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Chunyu Tian ◽  
Hong Chang ◽  
Xiaojin La ◽  
Ji-an Li ◽  
Leilei Ma
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Fasting Blood Glucose ◽  
Min6 Cells

Background. Wushenziye formula (WSZYF), composed of Radix Polygoni Multiflori Preparata, Mori fructus, Mori folium, and Cassiae semen, is effective in the treatment of type 2 diabetes mellitus (T2DM). Aim. In this study, we aimed to explore the effects and the underlying mechanisms of WSZYF on inhibiting pancreatic β cell apoptosis and improving insulin resistance (IR) in T2DM. Methods. A T2DM model was induced by Goto-Kakizaki diabetes prone rats. Cell apoptosis model was induced in MIN6 cells. Results. In vivo, WSZYF decreased fasting blood glucose (FBG), insulin concentration, insulin resistance index, triglyceride (TG), total cholesterol (TC), and free fatty acids (FFA) in T2DM rats. Meanwhile, WSZYF ameliorated impairments in the morphology and structure of pancreatic tissues. In vitro, WSZYF enhanced cell viability and promoted insulin secretion in the apoptosis model of MIN6 cells. Furthermore, WSZYF modulated the expressions of apoptosis-related molecules by increasing the expressions of MEK1/2, p-MEK1/2, ERK1/2, and p-ERK1/2 and decreasing the cleaved-caspase-3 expression. Conclusion. These findings indicate that WSZYF may become a new drug candidate in the treatment of T2DM and its antidiabetic mechanism is probably inhibiting pancreatic β cell apoptosis by modulating the MEK-ERK-Caspase-3 signaling pathway.

scholarly journals Role of TLR4/MyD88/NF-κB signaling in heart and liver-related complications in a rat model of type 2 diabetes mellitus

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Jiajia Tian ◽  
Yanyan Zhao ◽  
Lingling Wang ◽  
Lin Li
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Rat Model ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Primary Response ◽  
Monocyte Chemoattractant Protein 1

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.

scholarly journals Ameliorative Effect and Mechanism of the Purified Anthraquinone-Glycoside Preparation from Rheum Palmatum L. on Type 2 Diabetes Mellitus

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1454 ◽  
Author(s):  
Fang-Rong Cheng ◽  
Hong-Xin Cui ◽  
Ji-Li Fang ◽  
Ke Yuan ◽  
Ying Guo
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Cell Apoptosis ◽  
Fasting Blood Glucose ◽  
Β Cell ◽  
Diabetes Mellitus Group ◽  
Rheum Palmatum

Rheum palmatum L. is a traditional Chinese medicine with various pharmacological properties, including anti-inflammatory, antibacterial, and detoxification effects. In this study, the mechanism of the hypoglycemic effect of purified anthraquinone-Glycoside from Rheum palmatum L. (PAGR) in streptozotocin (STZ) and high-fat diet induced type 2 diabetes mellitus (T2DM) in rats was investigated. The rats were randomly divided into normal (NC), T2DM, metformin (Met), low, middle (Mid), and high (Hig) does of PAGR groups. After six weeks of continuous administration of PAGR, the serum indices and tissue protein expression were determined, and the pathological changes in liver, kidney, and pancreas tissues were observed. The results showed that compared with the type 2 diabetes mellitus group, the fasting blood glucose (FBG), total cholesterol (TC), and triglyceride (TG) levels in the serum of rats in the PAGR treatment groups were significantly decreased, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels were noticeably increased. The expression of Fas ligand (FasL), cytochrome C (Cyt-c), and caspase-3 in pancreatic tissue was obviously decreased, and the pathological damage to the liver, kidney, and pancreas was improved. These indicate that PAGR can reduce oxidative stress in rats with diabetes mellitus by improving blood lipid metabolism and enhancing their antioxidant capacity, thereby regulating the mitochondrial apoptotic pathway to inhibitβ-cell apoptosis and improve β-cell function. Furthermore, it can regulate Fas/FasL-mediated apoptosis signaling pathway to inhibit β-cell apoptosis, thereby lowering blood glucose levels and improving T2DM.

scholarly journals N1-Methylnicotinamide Improves Hepatic Insulin Sensitivity via Activation of SIRT1 and Inhibition of FOXO1 Acetylation

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jingfan Zhang ◽  
Yu Chen ◽  
Cong Liu ◽  
Ling Li ◽  
Ping Li
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Related Proteins

Objective. To explore the effects of N1-methylnicotinamide (MNAM) on insulin resistance and glucose metabolism in obese type 2 diabetes mellitus (T2DM) mice and regulatory mechanisms of the NAD-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box protein O1 (FOXO1) pathway. Methods. Blood glucose and insulin levels were examined in mice. HE and oil red O staining were used to observe the effects of MNAM on liver lipid deposition in ob/ob mice. Real-time PCR and Western blotting were used to detect expression of gluconeogenesis, insulin signaling-related proteins, and SIRT1/FOXO1 pathway-related proteins. L-O2 cells were cultured as a model of insulin resistance, and MNAM and SIRT1 inhibitors were administered in vivo. Residual glucose and insulin signaling-related proteins were detected and the mechanisms associated with the SIRT1/FOXO1 signaling pathway in insulin resistance explored. Results. MNAM can effectively reduce levels of fasting blood glucose and insulin, improve liver morphology, and reduce lipid accumulation in obese type 2 diabetes mellitus mice. MNAM also downregulates the key proteins in the gluconeogenesis pathway in the liver, upregulates Sirt1 expression, and reduces acetylation of the FOXO1 protein. In vitro, MNAM could promote the glucose uptake capacity of L-O2 cells induced by palmitic acid (PA), a saturated fatty acid that induces IR in various scenarios, including hepatocytes, improving insulin resistance. As Sirt1 expression was inhibited, the reduction of hepatocyte gluconeogenesis and the regulation of the insulin signaling pathway by MNAM were reversed. Conclusion. MNAM activates SIRT1 and inhibits acetylation of FOXO1, which in turn regulates insulin sensitivity in type 2 diabetic mice, leading to a reduction of hepatic glucose output and improvement of insulin resistance.

scholarly journals Relationship Between Orexin-A and Insulin Resistance in Patients with Type 2 Diabetes Mellitus

2021 ◽  
pp. 779-786
Author(s):  
Chinar Hameed Sadiq ◽  
Ridha H. Hussein ◽  
Ismail M. Maulood
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Enzyme Linked Immunosorbent Assay ◽  
Orexin A

Background: Orexin-A is an orexigenic hormone that plays an important role in the metabolism of blood glucose, insulin, and insulin resistance (IR). The pathogenesis of type 2 diabetes mellitus (T2DM) is related to the abnormality in insulin and IR. However, no sufficient studies to date have clearly shown the association of orexin-A with biochemical parameters related to T2DM. Objectives: The aim of this study was to determine the relation of orexin-A with IR and how they associate with physiological changes in T2DM patients. Understanding this relation will offer some pharmacological tools to reduce some complications in diabetes. Materials and Methods: A total of 41 T2DM and 43 non-DM subjects, aged between 40-60 years with body mass index (BMI) ≤25 kg/m2, participated in the present study. Fasting serum orexin-A, IR, fasting blood glucose (FBG), glycated hemoglobin (HbA1C), lipid profile, liver enzymes (alanine aminotransferase (ALT) and aspartate transaminase (AST)), nitric oxide (NO), and malondialdehyde (MDA) parameters were evaluated. Orexin-A was evaluated by using enzyme-linked immunosorbent assay (ELISA). For statistical analysis, GraphPad Prism 7.0 and SPSS version 24.0 programs were used. Results: Orexin-A was positively correlated with blood pressure, FBG, HbA1c, insulin, and IR but inversely related to insulin sensitivity (IS), leptin, and gender. Stepwise multiple regression presented HOMA-IR, diastolic blood pressure, and very-low-density lipoprotein-cholesterol as predictors for orexin-A. The area under control value showed orexin-A, FBG, HbA1c, HOMA-IR, IS, ALT, AST, NO and MDA as biomarkers for T2DM disease. Conclusion: Orexin-A has a predictive ability to diagnose T2DM, as it is significantly associated with hyperglycemia, IR, and IS.

scholarly journals Prognostic factors for the carbohydrate metabolism normalization in patients with type 2 diabetes mellitus and obesity using liraglutide 3.0 mg per day

2021 ◽  
Vol 93 (10) ◽  
pp. 1203-1208
Author(s):  
Igor A. Sklyanik ◽  
Marina V. Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Carbohydrate Metabolism ◽  
Fasting Blood Glucose ◽  
The Body ◽  
Hypoglycemic Effect ◽  
Antihyperglycemic Therapy

Background. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are innovative drugs that effectively reduce glycemic levels and overweight in patients with type 2 diabetes mellitus (T2DM). However, the criteria for predicting the hypoglycemic effect of this group of drugs have not been practically defined. Aim. To assess the factors contributing to the achievement the glycemia normalization in patients with diabetes mellitus and obesity by adding to antihyperglycemic therapy (AT) a drug from the GLP-1 RA group liraglutide 3.0 mg per day. Materials and methods. A single-center, prospective, non-randomized study was provided. The objects of the study were patients with T2DM and obesity (n=22). Liraglutide 3.0 mg per day was added to the current AT of patients. Initially, the parameters of carbohydrate metabolism, hormones of the incretin system on an empty stomach and during the mixed-meal test, insulin resistance using the euglycemic hyperinsulinemic clamp test, and body composition were studied. After 9 months of therapy, all studies were repeated and a search for possible predictors of the carbohydrate metabolism normalization was made. Results. The body mass index of patients decreased from 42.4 [37.7; 45.0] to 35.9 [33.0; 40.9] kg/m2. Fasting blood glucose and glycated hemoglobin levels decreased from 9.02 [7.40; 11.37] mmol/L and 7.85 [7.43; 8.65]% up to 5.90 [5.12; 6.18] mmol/L and 6.40 [5.90; 6.60]%, respectively. 14 (63.6%) patients reached normoglycemia. Insulin resistance according to the clamp test did not change over the study. Basal concentrations of oxyntomodulin, glycentin and the area under the GLP-1, oxyntomodulin, glycentin curve significantly decreased 9 months after liraglutide administration. The prognostic marker of the achievement of normoglycemia during therapy with liraglutide 3.0 mg/day is the level of endogenous GLP-15.5 pmol/L before the appointment of arGPP-1 therapy. Conclusion. The concentration of endogenous GLP-1 before the appointment of liraglutide therapy at a dose of 3.0 mg per day can be used for prediction the drug hypoglycemic effect and achieving normoglycemia possibility.

Sign in / Sign up

Export Citation Format

Share Document