scholarly journals Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice fed on a chow diet

2014 ◽  
Vol 221 (3) ◽  
pp. 469-480 ◽  
Author(s):  
Xuefeng Yang ◽  
Shuang Mei ◽  
Haihua Gu ◽  
Huailan Guo ◽  
Longying Zha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Chronic Exposure ◽  
Cholesterol Content ◽  
Chow Diet ◽  
Ectopic Fat ◽  
Β Cells ◽  
Liver And Pancreas

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.

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

scholarly journals The Effect of Ethanol and Ethyl Acetate Fraction of Chayote fruit (Sechium edule Jacq. Swartz) on the Oxidative Stress and Insulin Resistance of Male White Rat Model Type 2 Diabetes Mellitus

2020 ◽  
Vol 8 (A) ◽  
pp. 962-969
Author(s):  
Jekson Martiar Siahaan ◽  
Syaffruddin Illyas ◽  
Dharma Lindarto ◽  
Marline Nainggolan
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Ethyl Acetate ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Insulin Level ◽  
Ethyl Acetate Fraction ◽  
Sechium Edule

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.

scholarly journals Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues

2019 ◽  
Vol 8 (9) ◽  
pp. 1385 ◽  
Author(s):  
Burgos-Morón ◽  
Abad-Jiménez ◽  
Marañón ◽  
Iannantuoni ◽  
Escribano-López ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Β Cells ◽  
The Relationship ◽  
And Oxidative Stress

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

scholarly journals Insulin: The Friend and the Foe in the Development of Type 2 Diabetes Mellitus

2020 ◽  
Vol 21 (5) ◽  
pp. 1770
Author(s):  
Nadia Rachdaoui
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Cell Mass ◽  
Β Cells ◽  
Β Cell ◽  
Peripheral Insulin Resistance

Insulin, a hormone produced by pancreatic β-cells, has a primary function of maintaining glucose homeostasis. Deficiencies in β-cell insulin secretion result in the development of type 1 and type 2 diabetes, metabolic disorders characterized by high levels of blood glucose. Type 2 diabetes mellitus (T2DM) is characterized by the presence of peripheral insulin resistance in tissues such as skeletal muscle, adipose tissue and liver and develops when β-cells fail to compensate for the peripheral insulin resistance. Insulin resistance triggers a rise in insulin demand and leads to β-cell compensation by increasing both β-cell mass and insulin secretion and leads to the development of hyperinsulinemia. In a vicious cycle, hyperinsulinemia exacerbates the metabolic dysregulations that lead to β-cell failure and the development of T2DM. Insulin and IGF-1 signaling pathways play critical roles in maintaining the differentiated phenotype of β-cells. The autocrine actions of secreted insulin on β-cells is still controversial; work by us and others has shown positive and negative actions by insulin on β-cells. We discuss findings that support the concept of an autocrine action of secreted insulin on β-cells. The hypothesis of whether, during the development of T2DM, secreted insulin initially acts as a friend and contributes to β-cell compensation and then, at a later stage, becomes a foe and contributes to β-cell decompensation will be discussed.

scholarly journals Designing a late-stage type 2 diabetes mellitus model with brain insulin resistance and oxidative stress

2021 ◽  
Author(s):  
Rocío Redondo-Castillejo ◽  
Marina Hernández-Martín ◽  
Luis García-García ◽  
Juana Benedí ◽  
Adrián Macho-González ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Late Stage ◽  
Brain Insulin ◽  
Brain Insulin Resistance ◽  
And Oxidative Stress

scholarly journals Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ping Wang ◽  
Huili Liu ◽  
Li Chen ◽  
Yingli Duan ◽  
Qunli Chen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Whole Body ◽  
Glucokinase Activator ◽  
Liver And Pancreas

Glucokinase (GK) plays a critical role in the control of whole-body glucose homeostasis. We investigated the possible effects of a novel glucokinase activator (GKA), HMS5552, to the GK in rats with type 2 diabetes mellitus (T2DM). Male Sprague-Dawley (SD) rats were divided into four groups: control group, diabetic group, low-dose (10 mg/kg) HMS5552-treated diabetic group (HMS-L), and high-dose (30 mg/kg) HMS5552-treated diabetic group (HMS-H). HMS5552 was administered intragastrically to the T2DM rats for one month. The levels of total cholesterol, triglyceride, fasting plasma insulin (FINS), and glucagon (FG) were determined, and an oral glucose tolerance test was performed. The expression patterns of proteins and genes associated with insulin resistance and GK activity were assayed. Compared with diabetic rats, the FINS level was significantly decreased in the HMS5552-treated diabetic rats. HMS5552 treatment significantly lowered the blood glucose levels and improved GK activity and insulin resistance. The immunohistochemistry, western blot, and semiquantitative RT-PCR results further demonstrated the effects of HMS5552 on the liver and pancreas. Our data suggest that the novel GKA, HMS5552, exerts antidiabetic effects on the liver and pancreas by improving GK activity and insulin resistance, which holds promise as a novel drug for the treatment of T2DM patients.

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