Arsenic Induces Diabetic Effects Through Beta-Cell Dysfunction And Increased Gluconeogenesis In Mice

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Arsenic as a potential risk factor for type 2 diabetes had been received attention recently.

Insulin resistance might be not diabetic reason effects caused by iAs, indicating that diabetogenic mechanism effects of iAs exposure is different from the mechanism associated with traditional risk factors -reduced type 2 diabetes. Our data suggested that iAs exposure could cause pre diabetic effects by altering the lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and worsen diabetic effects in diabetes individual by these processes. Arsenic roles on development of diabetes are unclear. In this study, we compared inorganic influences arsenic on normal and diabetic mice by systems xicology approaches. Generally, it is interesting that iAs exposure could improve the insulin sensitivity based on the insulin lerance testing by glucose activation ‘uptakerelated’ genes and enzymes in normal and diabetic anybody. IAs exposure worsened the glucose lerance in diabetic mice, which might be since increased gluconeogenesis and impairment of pancreatic βcell function. It caused the pancreatic βcell dysfunction and increased gluconeogenesis and oxidative damages in liver, although iAs exposure did not change glucose lerance in normal mice.

Diabetes mellitus characterized by hyperglycemia is an increasing worldwide health problemIt is largely classified into ‘insulin dependent’ diabetes mellitus and ‘noninsulindependent’ diabetes mellitus.

The type 2 diabetes makes up more than 90percent of all diabetes casesEstablished risk factors for T2D, such as genetics, diet and lifestyle, do not fully explain the increase in this disease. Epidemiological studies carried out in Bangladesh6, Taiwan7, Mexico8, and United States9 have shown a strong diabetogenic effect of As in human populations mainly through As contaminated drinking water. Certainly, there is considerable interest in understanding nontraditional contribution risk factors to the diabetes epidemic, including environmental pollutants3, Among these environmental pollutants, arsenic exposure is paid much attentionAs is an ubiquitous xic metalloid in the environment. As a result, 500 µg/L3, Although some other researches concluded that the existing data were insufficient in support of an association between As and T2D10, data from human studies support an association between As and diabetes in population with arsenic ‘drinkingwater’ levels of &gt.

The T2D is characterized by disruptions in ‘whole body’ glucose homeostasis because of insulin resistance and impaired β cell dysfunctionindividuals with ‘β cell’ unable to sustain increases insulin secretion to compensate for insulin resistance will develop T2D, and thus inadequate ‘β cell’ function is essential to T2D12 course, In vitro studies using insulinoma cell lines implicate several pathways by which inorganic arsenic can affect pancreatic ‘βcell’ function to inhibit insulin expression and/or secretion14, Fu et al.

IAs influence on the development of diabetes in diabetic anyone also need to be specifically evaluated. And disturbed β cell function, as exposure dampened reactive oxygen species signaling involved in ‘glucose stimulated’ insulin secretion. With all that said. Diabetic comparison effects between normal and diabetic individuals might provide new insights to the mechanism of actions of iAs. You should take it into account. In vitro researches did not consider physiologically relevance. In animal studies, glucose levels, insulin regulation, insulin sensitivity and pancreatic effects were often the reported endpoint17,iAs and/or its methylated trivalent metabolites might cause insulin resistance by interacting with loads of elements involved in insulin signaling, including insulin receptor substrate, peroxisome proliferator activated receptorγ, protein kinase C and phosphatidylinositol 3 kinase 3, Although recent results supported a link between iAs exposure and diabetes, the findings from animal studies were inconsistent. The pre diabetic effects caused by iAs and its mechanism of actions in normal individual are unclear.

In this study, we compared iAs influences on normal C57BLKS/J mice and diabetic C57BKS/Leprdb mice.

The mice were exposed to iAs or deionized water for 16 weeks. Oxidative stress and damage, enzyme activities, gene expression profiles, and metabolic profiles in mice were determined. The diabetes related endpoints, including blood glucose levels, glucose tolerance, and insulin lerance were analyzed. Consequently, the gluconeogenesis, lipid metabolism, insulin resistance and function of ‘βcell’ were also analyzed. Based on above information, As roles on diabetes development were characterized.


Whenever peaking within 30 glucose min challenge model was carried out on individuals, as exposure decreased food intake of db/m mice, increased the food intake of db/db mice and fasting blood insulin in db/db control mice were significantly higher than those in db/m control mice showed the characteristic rapid rise in blood glucose.

One group was fed with deionized water, and another group with 3 mg/L sodium arsenite solution. All experimental processes were in accordance with NIH Guide for the Care and Use of Laboratory Animals. Daily water consumption was measured in all exposure groups. Body weights were determined every two weeks. Sodium arsenite was obtained from National Standard Material Center. Furthermore, the exposure duration was 16 weeks. The metabolic profiles in db/db mice exposed to iAs had higher similarity with those in db/db control mice, which were different with those in db/m mice with or without iAs exposure -reduced type 2 diabetes. 16 db/m mice were also randomly divided into two groups given deionized water with or without 3 mg/L sodium arsenite. Certainly, all mice were housed in ‘stainlesssteel’ cages under controlled conditions with 25 ± 3°C, 50 ± 5percent humidity and 12/12 h light/dark cycle. Following acclimation for one week, 16 db/db mice were randomly assigned to two groups. With all that said. C57BLKS/J db/m mice were chosen as normal control mice. With all that said. Seven week old male C57BKS/Leprdb mice were purchased from Model Animal Research Center of Nanjing University. The protocol was approved by the Committee on Animal Ethics Nanjing Experiments Military General Hospital. You should take this seriously. The sodium arsenite solution was prepared every week to minimize oxidation of As to As.

FBG and FBI were measured, after 16 week exposure of iAs. Additional samples of blood from tails were applied to measure FBI by the Mouse Insulin ELISA kit. HOMAIR and HOMA- β were calculated by the following equations Where units of FSI and FSG were mU/L and mmol/L. The foods for mice were deprived for 12 blood samples were collected from tails to measure FBG using a Glucose Monitoring System.

The OGTT and ITT were carried out conforming to previously described methodsOGTT were performed after 12 food h deprivation.

Blood glucose was measured as described for the OGTT. The ITT was conducted by intraperitoneal injection of 5 U/kg body weight insulin. Glucose was dissolved in diH2O and orally administered to the fasted mice. Now let me tell you something. Urine and feces samples were collected every two weeks and kept at −80° High performance liquid chromatography coupled with inductively coupled plasma mass spectrometry methods described by Van de Wiele et al50 were applied to detect and quantify iAs, iAs, MMA and DMA in urine and feces. Blood samples were collected from tail to measure the glucose levels before and 15, 30, 60, 90, and 120 min after glucose administration.

Parts of liver and pancreas were taken and fixed in 10% formalin solution. For SOD, GSH, and MDA, part of liver was homogenized, and supernatants were used for various estimations. After ’24 28’ h they were dehydrated in a grade alcohol series and embedded in paraffin wax. Hepatic oxidative stress and damage was determined by measurement of SOD, GSH, MDA, and 8OHdG. Make sure you scratch a comment about it. The protein contents, SOD, GSH, and MDA were measured using ELISA kits. For ‘8 OHdG’, genomic DNA of mouse livers were isolated by Genomic DNA Mini Preparation Kit, and the ‘8 OHdG’ levels were determined using a mouse 8 OHdG ELISA kit. On p of this, sections of 4 5″ μm thickness were stained with hematoxylineosin and taken photos by microscope for pathological analysis.

Hepatic levels PPARγ, FFA, Ppt1b, leptin, Na+K+-ATP, and Ca2+Mg2+-ATP were also determined by ELISA kits.

The cycling parameters were 50°C for 2 min, 95°C for 2 min, followed by 45 cycles of 95°C for 15 sec, 58 60″°C for 60 sec. Nonetheless, we performed qPCR analysis on a ABI7500 ‘RealTime’ PCR system using SYBR Select Master Mix qPCR reagent kit. Threshold cycles and dissociation curves were determined with 7500 Software v26, and gene expression levels were normalized to gene ‘β actin’. You should take this seriously. Total RNA in liver, adipocytes and pancreas were prepared using the Takara RNA Kit. Seriously. Each experiment was performed in triplicate. Standard curves and primer efficiencies were determined for all genes analyzed by qPCR.

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