scholarly journals Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Habib Yaribeygi ◽  
Thozhukat Sathyapalan ◽  
Stephen L. Atkin ◽  
Amirhossein Sahebkar

Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder characterized by chronic hyperglycemia and an inadequate response to circulatory insulin by peripheral tissues resulting in insulin resistance. Insulin resistance has a complex pathophysiology, and it is contributed to by multiple factors including oxidative stress. Oxidative stress refers to an imbalance between free radical production and the antioxidant system leading to a reduction of peripheral insulin sensitivity and contributing to the development of T2DM via several molecular mechanisms. In this review, we present the molecular mechanisms by which the oxidative milieu contributes to the pathophysiology of insulin resistance and diabetes mellitus.

2019 ◽  
Vol 25 (23) ◽  
pp. 2602-2606 ◽  
Author(s):  
Shahzad Khan ◽  
Mohammad A. Kamal

: Insulin resistance and type 2 Diabetes mellitus resulting in chronic hyperglycemia is a major health problem in the modern world. Many drugs have been tested to control hyperglycemia which is believed to be the main factor behind many of the diabetes-related late-term complications. Wogonin is a famous herbal medicine which has been shown to be effective in controlling diabetes and its complications. In our previous work, we showed that wogonin is beneficial in many ways in controlling diabetic cardiomyopathy. In this review, we mainly explained wogonin anti-hyperglycemic property through AKT/GLUT4 pathway. Here we briefly discussed that wogonin increases Glut4 trafficking to plasma membrane which allows increased entry of glucose and thus alleviates hyperglycemia. Conclusion: Wogonin can be used as an anti-diabetic and anti-hyperglycemic drug and works via AKT/GLUT4 pathway.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1236
Author(s):  
Jesús Burillo ◽  
Patricia Marqués ◽  
Beatriz Jiménez ◽  
Carlos González-Blanco ◽  
Manuel Benito ◽  
...  

Type 2 diabetes mellitus is a progressive disease that is characterized by the appearance of insulin resistance. The term insulin resistance is very wide and could affect different proteins involved in insulin signaling, as well as other mechanisms. In this review, we have analyzed the main molecular mechanisms that could be involved in the connection between type 2 diabetes and neurodegeneration, in general, and more specifically with the appearance of Alzheimer’s disease. We have studied, in more detail, the different processes involved, such as inflammation, endoplasmic reticulum stress, autophagy, and mitochondrial dysfunction.


2020 ◽  
Vol 8 (A) ◽  
pp. 962-969
Author(s):  
Jekson Martiar Siahaan ◽  
Syaffruddin Illyas ◽  
Dharma Lindarto ◽  
Marline Nainggolan

BACKGROUND: Oxidative stress in type 2 diabetes mellitus (T2D) causes insulin resistance and disordered insulin secretion. Pathomechanisms of T2D consist of dysfunctional pancreatic β-cell and insulin resistance caused by free radical (reactive oxygen species and reactive nitrogen species) that produced from the glucose metabolism pathway. Insulin resistance can be measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Oxidative stress can measure through the activities of malondialdehyde (MDA) and superoxide dismutase (SOD). AIM: This research aims to study the potential of chayote (Sechium edule Jacq. Swartz) to be used as antihyperglycemic in T2D. MATERIALS AND METHODS: This research was conducted with a post-test randomized controlled group design. Eleven groups with four male rats each were used. Normal untreated rats were treated under ad libitum feeding and drinking condition. Meanwhile, the rat models were induced with the combination of 45 mg/kg b.w. streptozotocin, 110 mg/kg b.w. nicotinamide, 40.5 mg/kg b.w. metformin, high-fat diet, and/or chayote extract. The chayote extract was orally administered to the rat in the form of ethanol extract and/or ethyl acetate fraction, with three dosages of 45 mg/kg b.w., 100 mg/kg b.w., and 150 mg/kg b.w. for each extract type. The body weight, glucose level, insulin level, MDA, and SOD activities were measured. The HOMA-IR was used. RESULTS: The lowest body weight of the rat model in week 0 was 145 ± 25.31, founded in Group H that was treated with ethyl acetate fraction of chayote extract (45 mg/kg b.w.). The lowest blood sugar level in the group with 2 h glucose load was 112.5 ± 27.00 on average, found in Group G that was treated with chayote ethanolic extract (150 mg/kg b.w.). The highest SOD in the group treated with chayote extract was 1.27 ± 0.20, founded in Group H treated with ethyl acetate 45 mg/kg b.w. The lowest level of MDA was 0.86 ± 0.70 in Group H treated with ethyl acetate 45 mg/kg b.w. The lowest fasting blood sugar spectrophotometer level was 150.54 ± 17.24 mg/dl in Group K with metformin treatment, followed by 155.16 ± 31.92 mg/dl in Group K treated 45 mg/kg b.w. ethanol treatment. The highest insulin level was 6.14 ± 0.71, founded in Group F that was treated with chayote ethanolic extract 100 mg/kg b.w. The lowest measurement of HOMA-IR was 0.16 ± 0.80 in Group E treated with ethanol extract of chayote 45 mg/kg b.w. CONCLUSION: Ethanol extract and fractionation of chayote work as an antioxidant and anti-insulin resistance.


Author(s):  
Gangaram Bhadarge ◽  
Pratibha Dawande ◽  
Nandkishor Bankar ◽  
Raunak Kotecha

Introduction: Zn supplementation improved glutathione peroxidase enzyme activity and decreased malondialdehyde and nitric oxide levels in diabetic rats, revealing Zn's defensive effect against oxidative stress in type 2 diabetes. The investigators have discovered that consuming Zn increased liver function and protected pancreatic tissue from damage caused by diabetes. Since Zn also prevents chronic hyperglycemia, it helps to minimize oxidative stress caused by type 2 diabetes. Diabetes mellitus (DM) is a global health problem that affects more than 3 million people worldwide (16% of population). Chronic hyperglycemia causes oxidative stress in diabetic patients by the development of free radicals (oxidants) and lowering the antioxidant protection mechanism. Aim: Glycaemic Regulation with Zinc Combination in Type 2 Diabetes Mellitus. Materials and Methods: Faculty of Medicine and Diabetic Opd, Datta Meghe Mediсаl Соllege and Shаlinitаi Meghe Hоsрitаl аnd Reseаrсh Сenter, Nаgрur in соllаbоrаtion with Dаttа Meghe Institute оf Mediсаl Sсienсes Deemed to be University, Sаwаngi, Wаrdhа, Mаhаrаshtrа. Results: The mean Zn level was 12.213±2.342in all participants and 9.121±1.782 in the control group, whereas it was significantly low (9.121±1.782) in the diabetic group, and there was statistically significant difference in Zn levels between the controls and the diabetic group (P < 0.001).FBS, HbA1C, serum Zinc mean effects between control and patients showed statistically significant differences in type 2 diabetes mellitus (P <0.0001). Conclusion: Our findings show that people with diabetes have lower levels of Zn than healthy people. The cause and effect of the association between very low levels of Zn and the progression of diabetes, or diabetes that causes Zn deficiency, is still unknown. Low levels of Zn are associated with poor glycemic control, and poor glycemic control is a good indication of Zn deficiency, as there was a negative association between serum Zn and FBS and HBA1C. If diabetic patients have low glycemic regulation, a long history of diabetes, obesity, or are over the age of 50, we look to assess their levels in Zn so that Zn alternative treatment can begin to release oxidative stress in this high-risk group.


2020 ◽  
Vol 21 (17) ◽  
pp. 6275 ◽  
Author(s):  
Unai Galicia-Garcia ◽  
Asier Benito-Vicente ◽  
Shifa Jebari ◽  
Asier Larrea-Sebal ◽  
Haziq Siddiqi ◽  
...  

Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.


Author(s):  
Eric C. Westman ◽  
Emily Maguire ◽  
William S. Yancy

Obesity and type 2 diabetes mellitus (T2DM) have reached epidemic proportions worldwide. While characterized by chronic hyperglycemia, the underlying cause of T2DM is insulin resistance—most often related to an increase in abdominal adiposity caused by obesity. The goal of treatment of T2DM is to put the disease into remission by targeting the underlying insulin resistance. The observation that dietary carbohydrate is the major factor to cause glycosuria and hyperglycemia, has been known since the early days of modern medicine. As a result, low-carbohydrate, ketogenic diets were employed to treat obesity and diabetes in the nineteenth and early twentieth centuries. This chapter reviews the rationale and recent clinical research supporting the use of a low-carbohydrate, ketogenic diet in individuals with obesity and diabetes. For individuals affected by obesity-related T2DM, clinical studies have shown that carbohydrate restriction and weight loss can improve hyperglycemia, obesity, and T2DM.


2018 ◽  
Vol 19 (11) ◽  
pp. 3342 ◽  
Author(s):  
Jasmine Plows ◽  
Joanna Stanley ◽  
Philip Baker ◽  
Clare Reynolds ◽  
Mark Vickers

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.


2014 ◽  
Vol 221 (3) ◽  
pp. 469-480 ◽  
Author(s):  
Xuefeng Yang ◽  
Shuang Mei ◽  
Haihua Gu ◽  
Huailan Guo ◽  
Longying Zha ◽  
...  

We have previously shown that insulin plays an important role in the nutrient-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical type 2 diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were treated with glargine once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and cholesterol content in mitochondria in tissues. Cholesterol content in mitochondria and its association with oxidative stress in cultured hepatocytes and β-cells were also examined. Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased cholesterol content in mitochondria of liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β-cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce typical T2DM in normal mice fed on a chow diet.


2019 ◽  
Vol 17 (2) ◽  
pp. 153-163 ◽  
Author(s):  
Muhammad A. Abdul-Ghani ◽  
Amin Jayyousi ◽  
Ralph A. DeFronzo ◽  
Nidal Asaad ◽  
Jassim Al-Suwaidi

Insulin resistance (IR) is a cardinal feature of type 2 diabetes mellitus (T2DM). It also is associated with multiple metabolic abnormalities which are known cardiovascular disease (CVD) risk factors. Thus, IR not only contributes to the development of hyperglycemia in T2DM patients, but also to the elevated CVD risk. Improving insulin sensitivity is anticipated to both lower the plasma glucose concentration and decrease CVD risk in T2DM patients, independent of glucose control. We review the molecular mechanisms and metabolic consequences of IR in T2DM patients and discuss the importance of addressing IR in the management of T2DM.


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