scholarly journals Antioxidant Roles of SGLT2 Inhibitors in the Kidney

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 143
Author(s):  
Carmen Llorens-Cebrià ◽  
Mireia Molina-Van den Bosch ◽  
Ander Vergara ◽  
Conxita Jacobs-Cachá ◽  
Maria José Soler
Keyword(s):  
Oxidative Stress ◽  
Cell Function ◽  
Redox System ◽  
High Energy ◽  
Sglt2 Inhibitors ◽  
Enzymatic Reactions ◽  
Cellular Processes ◽  
Proximal Tubular ◽  
Antioxidant Mechanisms

The reduction-oxidation (redox) system consists of the coupling and coordination of various electron gradients that are generated thanks to serial reduction-oxidation enzymatic reactions. These reactions happen in every cell and produce radical oxidants that can be mainly classified into reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS modulate cell-signaling pathways and cellular processes fundamental to normal cell function. However, overproduction of oxidative species can lead to oxidative stress (OS) that is pathological. Oxidative stress is a main contributor to diabetic kidney disease (DKD) onset. In the kidney, the proximal tubular cells require a high energy supply to reabsorb proteins, metabolites, ions, and water. In a diabetic milieu, glucose-induced toxicity promotes oxidative stress and mitochondrial dysfunction, impairing tubular function. Increased glucose level in urine and ROS enhance the activity of sodium/glucose co-transporter type 2 (SGLT2), which in turn exacerbates OS. SGLT2 inhibitors have demonstrated clear cardiovascular benefits in DKD which may be in part ascribed to the generation of a beneficial equilibrium between oxidant and antioxidant mechanisms.

scholarly journals Lipotoxicity and β-Cell Failure in Type 2 Diabetes: Oxidative Stress Linked to NADPH Oxidase and ER Stress

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3328
Author(s):  
Eloisa Aparecida Vilas-Boas ◽  
Davidson Correa Almeida ◽  
Leticia Prates Roma ◽  
Fernanda Ortis ◽  
Angelo Rafael Carpinelli
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Nadph Oxidase ◽  
Er Stress ◽  
Cell Function ◽  
Caloric Intake ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

A high caloric intake, rich in saturated fats, greatly contributes to the development of obesity, which is the leading risk factor for type 2 diabetes (T2D). A persistent caloric surplus increases plasma levels of fatty acids (FAs), especially saturated ones, which were shown to negatively impact pancreatic β-cell function and survival in a process called lipotoxicity. Lipotoxicity in β-cells activates different stress pathways, culminating in β-cells dysfunction and death. Among all stresses, endoplasmic reticulum (ER) stress and oxidative stress have been shown to be strongly correlated. One main source of oxidative stress in pancreatic β-cells appears to be the reactive oxygen species producer NADPH oxidase (NOX) enzyme, which has a role in the glucose-stimulated insulin secretion and in the β-cell demise during both T1 and T2D. In this review, we focus on the acute and chronic effects of FAs and the lipotoxicity-induced β-cell failure during T2D development, with special emphasis on the oxidative stress induced by NOX, the ER stress, and the crosstalk between NOX and ER stress.

Probucol preserves pancreatic β-cell function through reduction of oxidative stress in type 2 diabetes

2002 ◽  
Vol 57 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Shin-ichi Gorogawa ◽  
Yoshitaka Kajimoto ◽  
Yutaka Umayahara ◽  
Hideaki Kaneto ◽  
Hirotaka Watada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Cell Function ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Β Cell Function

Generation of Free Radicals and Messenger Function

1995 ◽  
Vol 20 (3) ◽  
pp. 280-288 ◽  
Author(s):  
John C. Carlson ◽  
Masaaki Sawada
Keyword(s):  
Free Radicals ◽  
Cell Function ◽  
Control Cell ◽  
Muscle Cells ◽  
Cell Types ◽  
Signal Pathways ◽  
Cellular Processes ◽  
Toxic Agents ◽  
Intracellular Messengers ◽  
Antioxidant Mechanisms

Free radicals are toxic agents that are produced as by-products of metabolic activity. A number of antioxidant mechanisms work to protect cells from damage. Recent evidence indicates, however, that free radicals and related oxidants such as hydrogen peroxide may also have a beneficial role, working as messengers to control cell function. These agents are generated in response to agonists, production is regulated by intracellular signal pathways, and they appear to be used to control particular cellular processes. Free radicals may perform these functions in a number of cell types. Also, they are produced in muscles and there is evidence that they may work as messengers in smooth muscle cells. Key words: phospholipases, intracellular messengers, regulation of function, muscle cells

scholarly journals Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients

2011 ◽  
Vol 106 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Pál Brasnyó ◽  
Gergő A. Molnár ◽  
Márton Mohás ◽  
Lajos Markó ◽  
Boglárka Laczy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Type 2 Diabetic Patients ◽  
Β Cell Function ◽  
Type 2 Diabetic

Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. After an initial general examination (including blood chemistry), nineteen patients enrolled in the 4-week-long double-blind study were randomly assigned into two groups: a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo. Before and after the second and fourth weeks of the trial, insulin resistance/sensitivity, creatinine-normalised ortho-tyrosine level in urine samples (as a measure of oxidative stress), incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B (Akt) ratio in platelets were assessed and statistically analysed. After the fourth week, resveratrol significantly decreased insulin resistance (homeostasis model of assessment for insulin resistance) and urinary ortho-tyrosine excretion, while it increased the pAkt:Akt ratio in platelets. On the other hand, it had no effect on parameters that relate to β-cell function (i.e. homeostasis model of assessment of β-cell function). The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway.

Structural Perspectives and Advancement of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes

2021 ◽  
Vol 17 ◽  
Author(s):  
Shivani Sharma ◽  
Amit Mittal ◽  
Shubham Kumar ◽  
Anu Mittal
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cell Function ◽  
Sglt2 Inhibitors ◽  
Health Care Practices ◽  
Sodium Glucose Cotransporter ◽  
Β Cell Function ◽  
Insulin Dependent ◽  
Glycemic Regulation

: Diabetes mellitus is an ailment that affects a large number of individuals worldwide and its pervasiveness has been predicted to increase later on. Every year, billions of dollars are spent globally on diabetes-related health care practices. Contemporary hyperglycemic therapies to rationalize type 2 diabetes mellitus (T2DM) mostly involve pathways that are insulin-dependent and lack effectiveness as the pancreas’ β-cell function declines more significantly. Homeostasis via kidneys emerges as a new and future strategy to minimize T2DM complications. This article covers the reabsorption of glucose mechanism in the kidneys, the functional mechanism of various Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, their structure and driving profile, and a few SGLT2 inhibitors now accessible in the market as well as those in different periods of advancement. The advantages of SGLT2 inhibitors are dose-dependent glycemic regulation changes with a significant reduction both in the concentration of HbA1c and body weight clinically and statistically. A considerable number of SGLT2 inhibitors have been approved by the FDA, while a few others, still in preliminaries, have shown interesting effects.

scholarly journals Oxidative Stress in Neurodegenerative Diseases: From a Mitochondrial Point of View

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Giovanna Cenini ◽  
Ana Lloret ◽  
Roberta Cascella
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Aging Process ◽  
Molecular Mechanisms ◽  
High Energy ◽  
Point Of View ◽  
Antioxidant Defenses ◽  
Mitochondrial Oxidative Stress ◽  
Cellular Processes

Age is the main risk factor for a number of human diseases, including neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, which increasing numbers of elderly individuals suffer. These pathological conditions are characterized by progressive loss of neuron cells, compromised motor or cognitive functions, and accumulation of abnormally aggregated proteins. Mitochondrial dysfunction is one of the main features of the aging process, particularly in organs requiring a high-energy source such as the heart, muscles, brain, or liver. Neurons rely almost exclusively on the mitochondria, which produce the energy required for most of the cellular processes, including synaptic plasticity and neurotransmitter synthesis. The brain is particularly vulnerable to oxidative stress and damage, because of its high oxygen consumption, low antioxidant defenses, and high content of polyunsaturated fats very prone to be oxidized. Thus, it is not surprising the importance of protecting systems, including antioxidant defenses, to maintain neuronal integrity and survival. Here, we review the role of mitochondrial oxidative stress in the aging process, with a specific focus on neurodegenerative diseases. Understanding the molecular mechanisms involving mitochondria and oxidative stress in the aging and neurodegeneration may help to identify new strategies for improving the health and extending lifespan.

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