Identification of Protein Kinase C Isoforms Involved in Type 1 Diabetic Encephalopathy in Mice

Zheng, Jiakun; Wang, Yue; Han, Song; Luo, Yanlin; Sun, Xiuli; Zhu, Ning; Zhao, Li; Li, Junfa

doi:10.1155/2018/8431249

Cited by 12 publications

(6 citation statements)

References 52 publications

(51 reference statements)

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“…Body weight and water and food intake were recorded once a week, and fasting blood glucose levels was assessed every 2 weeks from a tail vein blood sample using a OneTouch® Ultra blood glucose meter. Mice with blood glucose levels >11.1 mmol/L were selected as the diabetes model group for subsequent experiments [38]. In the present study, 26 diabetes model mice were obtained (26 of 32, 81.25%) and used for subsequent experiments.…”

Section: Methodsmentioning

confidence: 99%

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice

Fan

Han

Zhan

et al. 2019

Aging

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Both diabetes and Alzheimer’s disease are age-related disorders, and numerous studies have demonstrated that patients with diabetes are at an increased risk of cognitive dysfunction (CD) and Alzheimer’s disease, suggesting shared or interacting pathomechanisms. The present study investigated the role of abnormal gut microbiota in diabetes-induced CD and the potential underlying mechanisms. An intraperitoneal injection of streptozotocin administered for 5 consecutive days was used for establishing a diabetic animal model. Hierarchical cluster analysis of Morris water maze (MWM) performance indices (escape latency and target quadrant crossing) was adopted to classify the diabetic model mice into CD and Non-CD phenotypes. Both β-diversity and relative abundance of several gut bacteria significantly differed between the CD and Non-CD groups. Further, fecal bacteria transplantation from Non-CD mice, but not from CD mice, into the gut of pseudo-germ-free mice significantly improved host MWM performance, an effect associated with alterations in β-diversity and relative abundance of host gut bacteria. Collectively, these findings suggest that abnormal gut microbiota composition contributes to the onset of diabetes-induced CD and that improving gut microbiota composition is a potential therapeutic strategy for diabetes and related comorbidities.

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Section: Methodsmentioning

confidence: 99%

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice

Fan

Han

Zhan

et al. 2019

Aging

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“… 29 The membrane translocation levels of cPKCγ have been shown to decrease in the cortex and striatum of mice with diabetic encephalopathy. 19 In this study, we found that the levels of cPKCγ membrane translocation increased after MD, and neuron numbers did not change significantly in the deprived visual cortex, suggesting that increased cPKCγ activation levels were not induced by neuron numbers.…”

Section: Discussionmentioning

confidence: 50%

“…The mouse visual cortex was dissected and rapidly frozen in liquid nitrogen. Based on our previous work, 18 , 19 frozen samples were thawed and homogenized in Buffer A (50-mM Tris-Cl, pH 7.5; 1-mM EGTA; 2 mM-EDTA; 100-µM sodium vanadate; 50-nM okadaic acid; 50-mM potassium fluoride; 5-mM sodium pyrophosphate; and 5 µg/µL each of pepstatin A, chymostatin, leupeptin, and aprotinin). Homogenates were then centrifuged at 100,000 g for 30 minutes at 4°C, and the supernatants were collected as the cytosolic fraction.…”

Section: Methodsmentioning

confidence: 99%

Monocular Deprivation Affects Visual Cortex Plasticity Through cPKCγ-Modulated GluR1 Phosphorylation in Mice

Zhang

Han

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine how visual cortex plasticity changes after monocular deprivation (MD) in mice and whether conventional protein kinase C gamma (cPKCγ) plays a role in visual cortex plasticity. Methods cPKCγ membrane translocation levels were quantified by using immunoblotting to explore the effects of MD on cPKCγ activation. Electrophysiology was used to record field excitatory postsynaptic potential (fEPSP) amplitude with the goal of observing changes in visual cortex plasticity after MD. Immunoblotting was also used to determine the phosphorylation levels of GluR1 at Ser831. Light transmission was analyzed using electroretinography to examine the effects of MD and cPKCγ on mouse retinal function. Results Membrane translocation levels of cPKCγ significantly increased in the contralateral visual cortex of MD mice compared to wild-type (WT) mice ( P < 0.001). In the contralateral visual cortex, long-term potentiation (LTP) and the phosphorylation levels of GluR1 at Ser 831 were increased in cPKCγ +/+ mice after MD. Interestingly, these levels could be downregulated by cPKCγ knockout compared to cPKCγ +/+ +MD mice ( P < 0.001). Compared to the right eyes of WT mice, the amplitudes of a-waves and b-waves declined in deprived right eyes of mice after MD ( P < 0.001). There were no significant differences when comparing cPKCγ +/+ and cPKCγ −/− mice with MD. Conclusions cPKCγ participates in the plasticity of the visual cortex after MD, which is characterized by increased LTP in the contralateral visual cortex, which may be a result of cPKCγ-mediated phosphorylation of GluR1 at Ser 831.

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“…The organ indexes (organ weight/body weight) were statistically analyzed. According to the FBG values [ 22 , 23 ], the mice were divided into three groups as follows: control group (without ALX exposure), tolerant group (ALX exposure, nondiabetic mice with an FBG < 11.1 mmol/L), and sensitive group (ALX exposure, diabetic mice with an FBG ≥ 11.1 mmol/L).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of the Keap1/Nrf2 Signaling Pathway Significantly Promotes the Progression of Type 1 Diabetes Mellitus

Lou

Kong

et al. 2021

Oxidative Medicine and Cellular Longevity

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Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insulin deficiency due to pancreatic β-cell damage and leads to hyperglycemia. The precise molecular mechanisms of the etiology of T1DM are not completely understood. Oxidative stress and the antioxidant status of pancreatic β-cells play a vital role in the pathogenesis and progression of T1DM. The Keap1/Nrf2 signaling pathway plays a critical role in cellular resistance to oxidative stress. This study is aimed at investigating the role of the Keap1/Nrf2 signaling pathway in the progression of T1DM. An alloxan- (ALX-) stimulated T1DM animal model in wild-type (WT) and Nrf2 knockout (Nrf2-/-) C57BL/6J mice and a mouse pancreatic β-cell line (MIN6) were established. Compared with the tolerant (ALX exposure, nondiabetic) WT mice, the sensitive (ALX exposure, diabetic) WT mice exhibited higher blood glucose levels and lower plasma insulin levels. The Keap1/Nrf2 signaling pathway was significantly inhibited in the sensitive WT mice, which was reflected by overexpression of Keap1 and low expression of Nrf2, accompanied by a marked decrease in the expression of the antioxidative enzymes. Compared with WT mice, the Nrf2-/- mice had an increased incidence of T1DM and exhibited more severe pancreatic β-cell damage. The results of in vitro experiments showed that ALX significantly inhibited the viability and proliferation and promoted the apoptosis of MIN6 cells. ALX also markedly increased intracellular ROS production and caused DNA damage in MIN6 cells. In addition, the Keap1/Nrf2 signaling pathway was significantly inhibited in the damaged MIN6 cells. Moreover, Nrf2 silencing by transfection with Nrf2 siRNA markedly exacerbated ALX-induced MIN6 cell injury. Conclusively, this study demonstrates that inhibition of the Keap1/Nrf2 signaling pathway could significantly promote the incidence of T1DM. This study indicates that activation of Keap1/Nrf2 signaling in pancreatic β-cells may be a useful pharmacological strategy for the clinical prevention and treatment of T1DM.

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Identification of Protein Kinase C Isoforms Involved in Type 1 Diabetic Encephalopathy in Mice

Cited by 12 publications

References 52 publications

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice

Monocular Deprivation Affects Visual Cortex Plasticity Through cPKCγ-Modulated GluR1 Phosphorylation in Mice

Inhibition of the Keap1/Nrf2 Signaling Pathway Significantly Promotes the Progression of Type 1 Diabetes Mellitus

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