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autophagy AND insulin

Qian Yu, Bei Zhao, Qi He, Yuan Zhang, Xian-Bo Peng
microRNA (miR) has been shown to be involved in the treatment of diseases such as osteoarthritis (OA). This study aims to investigate the role of miR-206 in regulating insulin-like growth factor-1 (IGF-1) in chondrocyte autophagy and apoptosis in an OA rat model via the phosphoinositide 3-kinase (P13K)/protein kinase B (AKT)-mechanistic target of rapamycin (mTOR) signaling pathway. Wistar rats were used to establish the OA rat model, followed by the observation of histopathological changes, Mankin score, and the detection of IGF-1-positive expression and tissue apoptosis...
October 18, 2018: Journal of Cellular Biochemistry
Wu Lv, Jialin Zhang, Ao Jiao, Bowen Wang, Baomin Chen, Jie Lin
It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors which can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP...
October 12, 2018: Canadian Journal of Physiology and Pharmacology
Jing Pan, Yu-Qin Di, Yong-Bo Li, Cai-Hua Chen, Jin-Xing Wang, Xiao-Fan Zhao
Insulin promotes larval growth of insects by stimulating the synthesis of the steroid hormone 20-hydroxyecdysone (20E), which induces pupation and apoptosis. However, the mechanism underlying the coordinate regulation of insect pupation and apoptosis by these two functionally opposing hormones is still unclear. Here, using the lepidopteran insect and serious agricultural pest Helicoverpa armigera (cotton bollworm) as a model, we report that phosphoinositide-dependent kinase-1 (PDK1) and forkhead box O (FoxO) play key roles in these processes...
October 10, 2018: Journal of Biological Chemistry
Katarzyna Kornicka, Agnieszka Śmieszek, Jolanta Szłapka-Kosarzewska, Jennifer M Irwin Houston, Michael Roecken, Krzysztof Marycz
Endocrine disorders are becoming an increasing problem in both human and veterinary medicine. In recent years, more and more horses worldwide have been suffering from equine metabolic syndrome (EMS). This metabolic disorder is characterized by pathological obesity, hyperinsulinaemia, hyperglycaemia and insulin resistance. Although metabolic disorders, including diabetes, have been extensively studied, there are still no data on the molecular effects of EMS in horses. Thus, the aim of this study was to evaluate apoptosis, oxidative stress, autophagy and microRNA (miR) expression in multipotent intestinal epithelial stem cells (IECs) and pancreatic islets (PIs) isolated post mortem form healthy and EMS diagnosed horses...
October 8, 2018: International Journal of Molecular Sciences
Xueli Zhang, Yi Zhao, Yamin Liu, Yang Yuan, Hua Shao, Xiao Zheng
Metabolic disturbance is commonly observed in schizophrenia patients, and the metabolic impacts of atypical antipsychotics such as olanzapine (OLA) have received much attention. Drug naive schizophrenia patients display metabolic abnormality to varying degrees, but how this shapes the metabolic responses to chronic OLA exposure is unknown. Using high-fat diet (HFD, 8 weeks) induced obesity, here we explored the metabolic outcome of chronic OLA exposure in conditions of pre-existing metabolic disturbance. OLA treatment (2 mg/kg) for 4 weeks led to markedly reduced body weight and adiposity in obese mice, concomitant with reduced adipose inflammation and hepatic steatosis...
October 4, 2018: Biochemical Pharmacology
Mahdi Vazirian, Seyed Mohammad Nabavi, Samineh Jafari, Azadeh Manayi
Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme which monitors cellular energy status and regulates metabolism with energy balance. AMPK activation, as a master regulator of metabolism, plays role in key tissues like liver, skeletal muscles, and heart as well as central nervous system (CNS). Activation of the enzyme by indirect activators attracts scientific attentions to treat diabetes, obesity, cancer, and other related metabolic disorders like physiological and pathophysiological states in CNS...
October 2, 2018: Food and Chemical Toxicology
Gang Qian, Dandan Liu, Lili Hou, Mohammed Hamid, Xingxiang Chen, Fang Gan, Suquan Song, Kehe Huang
Ochratoxin A (OTA) could cause a variety of toxicological effects especially nephrotoxicity in animals and humans. Autophagy is a highly conserved metabolic process that plays an important role in the maintenance of cellular homeostasis under stress. However, the role of autophagy in OTA-induced nephrotoxicity is unknown. In the present study, we demonstrated that OTA treatment at 2.0-8.0 μM could increase cytotoxicity of PK-15 cells by inducing apoptosis as shown by the increased Annexin V/PI staining, increased caspase-3 and PARP cleavage and increased apoptotic nuclei...
October 1, 2018: Food and Chemical Toxicology
Yi-Fan Dang, Xiao-Ning Jiang, Fu-Lian Gong, Xiu-Li Guo
Rosiglitazone (ROSI), a member of thiazolidinediones (TZDs) which act as high-affinity agonists of the nuclear receptor peroxisome-proliferator-activated receptor-γ (PPARγ), is clinically used as an antidiabetic drug which could attenuate the insulin resistance associated with obesity, hypertension, and impaired glucose tolerance in humans. However, recent studies reported that ROSI had significant anticancer effects on various human malignant tumor cells. Mounting evidence indicated that ROSI could exert anticancer effects through PPARγ-dependent or PPARγ-independent ways...
September 29, 2018: Chemico-biological Interactions
Hai-Na Zhang, Ya-Juan Sun, Huai-Qiang He, Hong-Yan Li, Qiu-Li Xue, Zhong-Min Liu, Guang-Men Xu, Li-Hua Dong
Berberine presents therapeutic ability for various central nervous system disorders, including Alzheimer's disease and cerebral ischemia. The present study investigated the role of berberine in nerve regeneration and analyzed the potential mechanism mediated by berberine in hippocampal pyramidal neurons. Reverse transcription‑quantitative poylmerase chain reaction, western blot, TUNEL assay and immunofluorescence were used to analyze the therapeutic effects of berberine on nerve regeneration. Berberine treatment increased growth and viability of hippocampal pyramidal neurons...
September 24, 2018: Molecular Medicine Reports
Shaowei Zhao, Tina M Fortier, Eric H Baehrecke
Adult stem cells usually reside in specialized niche microenvironments. Accumulating evidence indicates that competitive niche occupancy favors stem cells with oncogenic mutations, also known as tumor-like stem cells. However, the mechanisms that regulate tumor-like stem cell niche occupancy are largely unknown. Here, we use Drosophila ovarian germline stem cells as a model and use bam mutant cells as tumor-like stem cells. Interestingly, we find that autophagy is low in wild-type stem cells but elevated in bam mutant stem cells...
October 8, 2018: Current Biology: CB
Marta Cruces-Sande, Rocío Vila-Bedmar, Alba C Arcones, Águeda González-Rodríguez, Patricia Rada, Virginia Gutiérrez-de-Juan, Javier Vargas-Castrillón, Paula Iruzubieta, Cristina Sánchez-González, Laura Formentini, Javier Crespo, Carmelo García-Monzón, María L Martínez-Chantar, Ángela M Valverde, Federico Mayor, Cristina Murga
Insulin resistance (IR) and obesity are important risk factors for non-alcoholic fatty liver disease (NAFLD). G protein-coupled receptor kinase 2 (GRK2) is involved in the development of IR and obesity in vivo. However, its possible contribution to NAFLD and/or non-alcoholic steatohepatitis (NASH) independently of its role on IR or fat mass accretion has not been explored. Here, we used wild-type (WT) or GRK2 hemizygous (GRK2±) mice fed a high-fat diet (HFD) or a methionine and choline-deficient diet (MCD) as a model of NASH independent of adiposity and IR...
September 24, 2018: Biochimica et biophysica acta. Molecular basis of disease
Diana L Cousminer, Emma Ahlqvist, Rajashree Mishra, Mette K Andersen, Alessandra Chesi, Mohammad I Hawa, Asa Davis, Kenyaita M Hodge, Jonathan P Bradfield, Kaixin Zhou, Vanessa C Guy, Mikael Åkerlund, Mette Wod, Lars G Fritsche, Henrik Vestergaard, James Snyder, Kurt Højlund, Allan Linneberg, Annemari Käräjämäki, Ivan Brandslund, Cecilia E Kim, Daniel Witte, Elin Pettersen Sørgjerd, David J Brillon, Oluf Pedersen, Henning Beck-Nielsen, Niels Grarup, Richard E Pratley, Michael R Rickels, Adrian Vella, Fernando Ovalle, Olle Melander, Ronald I Harris, Stephen Varvel, Valdemar E R Grill, Hakon Hakonarson, Philippe Froguel, John T Lonsdale, Didac Mauricio, Nanette C Schloot, Kamlesh Khunti, Carla J Greenbaum, Bjørn Olav Åsvold, Knud B Yderstræde, Ewan R Pearson, Stanley Schwartz, Benjamin F Voight, Torben Hansen, Tiinamaija Tuomi, Bernhard O Boehm, Leif Groop, R David Leslie, Struan F A Grant
OBJECTIVE: Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype. RESEARCH DESIGN AND METHODS: We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects ( n = 2,634 vs...
September 25, 2018: Diabetes Care
Jianqiang Hu, Shanjie Wang, Zhenyu Xiong, Zheng Cheng, Zhi Yang, Jie Lin, Tingting Wang, Xinyu Feng, Erhe Gao, Haichang Wang, Dongdong Sun
Diabetic cardiomyopathy (DCM) is characterized by cardiac microvascular endothelial cells (CMECs) injury and cardiomyocyte (CM) dysfunction. Exosomes mediated cellular communication between CMECs and CM has emerging roles in the pathogenesis of DCM, but the underlining mechanisms are unclear. Mammalian sterile 20-like kinase 1 (Mst1), a key component in Hippo pathway which participates in regulating organ size, apoptosis and autophagy, is involved in the development of DCM. We generated the endothelial-specific Mst1 transgenic mice (Tg-Mst1EC ) and constructed diabetic model with streptozotocin (STZ)...
November 2018: Biochimica et biophysica acta. Molecular basis of disease
Jonatan Zorea, Manu Prasad, Limor Cohen, Nan Li, Roman Schefzik, Susmita Ghosh, Barak Rotblat, Benedikt Brors, Moshe Elkabets
Genomic alterations (GA) in PIK3CA leads to the hyper-activation of the phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K) pathway in more than 20% of ovarian cancer (OC) patients. Therefore, PI3K therapies are under clinical evaluation for this subset of patients. Evidently, in clinical trials testing the efficacy of isoform-specific inhibitors of PI3K (PI3Ki), patients having a stable disease eventually relapse, as tumors become resistant to treatment. Hence, there is an urgent clinical need to develop new therapeutic combinations to improve the efficacy of PI3Ki in PIK3CA-driven OC patients...
September 20, 2018: Cell Death & Disease
Maroua Ferhat, Katsuhiko Funai, Sihem Boudina
SIGNIFICANCE: Alterations in adipose tissue function have profound consequences on whole body energy homeostasis because this tissue is central for fat accumulation, energy expenditure, glucose and insulin metabolism and hormonal regulation. With the obesity reaching epidemic proportions globally, it is important to understand the mechanisms leading to adipose tissue malfunction. Recent Advances: Autophagy has originally been viewed as an adaptive response to cellular stress, but in recent years, this process was shown to regulate important cellular processes...
September 20, 2018: Antioxidants & Redox Signaling
Kyota Aoyagi, Makoto Itakura, Toshiyuki Fukutomi, Chiyono Nishiwaki, Yoko Nakamichi, Seiji Torii, Tomohiko Makiyama, Akihiro Harada, Mica Ohara-Imaizumi
Dysfunctional mitochondria are observed in β-cells of diabetic patients, which are eventually removed by autophagy. VAMP7, a vesicular SNARE protein, regulates autophagosome formation to maintain mitochondrial homeostasis and control insulin secretion in pancreatic β-cells. However, its molecular mechanism is largely unknown. Here, we investigated the molecular mechanism of VAMP7-dependent autophagosome formation using VAMP7-deficient β-cells and β-cell derived Min6 cells. VAMP7 localised in Atg9a-resident vesicles of recycling endosomes (REs), which contributed to autophagosome formation, and interacted with Hrb, Syntaxin16, and SNAP-47...
September 12, 2018: Endocrinology
Min-Kyeong Lee, Jeong-Wook Choi, Youn Hee Choi, Taek-Jeong Nam
We investigated the protective effects of Pyropia yezoensis crude protein (PYCP) against dexamethasone (DEX)-induced myotube atrophy and its underlying mechanisms. DEX (3 mg/kg body weight, intraperitoneal injection) and PYCP (150 and 300 mg/kg body weight, oral) were administrated to mice for 18 days, and the effects of PYCP on DEX-induced muscle atrophy were evaluated. Body weight, calf thickness, and gastrocnemius and tibialis anterior muscle weight were significantly decreased by DEX administration ( p < 0...
September 11, 2018: Marine Drugs
Marte Molenaars, Georges E Janssens, Toon Santermans, Marco Lezzerini, Rob Jelier, Alyson W MacInnes, Riekelt H Houtkooper
Mutations in the clk-1 gene impair mitochondrial ubiquinone biosynthesis and extend lifespan in C. elegans . We demonstrate here that this life extension is linked to the repression of cytoplasmic mRNA translation, independent of the alleged nuclear form of CLK-1. Clk-1 mutations inhibit polyribosome formation similarly to daf-2 mutations that dampen insulin signaling. Comparisons of total versus polysomal RNAs in clk-1(qm30) mutants reveal a reduction in the translational efficiencies of mRNAs coding for elements of the translation machinery and an increase in those coding for the oxidative phosphorylation and autophagy pathways...
August 31, 2018: Life science alliance
Tanu Singh, Eric H Lee, Tiffiney R Hartman, Dara M Ruiz-Whalen, Alana M O'Reilly
Egg production declines with age in many species, a process linked with stem cell loss. Diet-dependent signaling has emerged as critical for stem cell maintenance during aging. Follicle stem cells (FSCs) in the Drosophila ovary are exquisitely responsive to diet-induced signals including Hedgehog (Hh) and insulin-IGF signaling (IIS), entering quiescence in the absence of nutrients and initiating proliferation rapidly upon feeding. Although highly proliferative FSCs generally exhibit an extended lifespan, we find that constitutive Hh signaling drives FSC loss and premature sterility despite high proliferative rates...
September 24, 2018: Developmental Cell
Tariq R Altamimi, Biswajit Chowdhury, Krishna K Singh, Liyan Zhang, Mohammad U Mahmood, Yi Pan, Adrian Quan, Hwee Teoh, Subodh Verma, Gary D Lopaschuk
BACKGROUND: We sought to determine if endothelial autophagy affects myocardial energy metabolism. METHODS: We used isolated working mouse hearts to compare cardiac function, energy metabolism, and ischemic response of hearts from endothelial cell-specific ATG7 knockout (EC-ATG7-/- ) mice to hearts from their wild-type littermates. We also conducted gene analyses on human umbilical vein endothelial cells incubated with scrambled small interfering RNA or small interfering ATG7...
August 2, 2018: Journal of Thoracic and Cardiovascular Surgery
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