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autophagy AND insulin

Ben C King, Erik Renström, Anna M Blom
Complement component C3 is central to the complement system, a humoral effector mechanism of innate immune defense. When activated, C3 covalently binds to target particles, marking them for uptake and clearance by phagocytosis. We now show that C3 also exists within the cytosol where it interacts with ATG16L1, and is therefore involved in the intracellular clearance and recycling of material by macroautophagy/autophagy in pancreatic beta cells. C3 is highly expressed in isolated human islets, and its expression is upregulated in islets isolated from diabetic patients and rodents, and correlates with patient HBA1c and body mass index (BMI)...
February 11, 2019: Autophagy
Giulia Coliva, Sofia Duarte, Dolores Pérez-Sala, Maria Fedorova
Cells employ multiple defence mechanisms to sustain a wide range of stress conditions associated with accumulation of modified self-biomolecules leading to lipo- and proteotoxicity. One of such mechanisms involves activation of the autophagy-lysosomal pathway for removal and degradation of modified lipids, proteins and even organelles. Biomolecules carbonylation, an irreversible oxidative modification, occurs in a variety of pathological conditions and is generally viewed as a marker of oxidative stress. Here, we used a model of rat primary cardiac cells to elucidate the role of autophagy-lysosomal pathway in the turnover of carbonylated biomolecules...
January 24, 2019: Redox Biology
Parvin Farzanegi, Amir Dana, Zeynab Ebrahimpoor, Mahdieh Asadi, Mohammad Ali Azarbayjani
Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disorder which is associated with accumulation of fats in the liver. It causes a wide variety of pathological effects such as non-alcoholic steatohepatitis (NASH) and cirrhosis, insulin resistance, obesity, hypertension, dyslipidaemia, diabetes and cardiovascular disease. The molecular mechanisms that cause the initiation and progression of NAFLD are not fully understood. Oxidative stress (OS) induced by reactive oxygen species (ROS) and inflammation are likely a significant mechanism which can lead to hepatic cell death and tissue injury...
February 8, 2019: European Journal of Sport Science
Hsin-Hsien Yu, Mao-Chih Hsieh, Szu-Yuan Wu, Edgar D Sy, Yan-Shen Shan
Background: Duodenal-jejunal bypass (DJB) is an important component of many types of current bariatric surgery including Roux-en-Y gastric bypass, mini-gastric bypass, biliopancreatic diversion, duodenal switch, and DJB plus sleeve gastrectomy. Surgery is often observed to ameliorate nonalcoholic steatohepatitis (NASH), but without a clearly delineated mechanism. In this study, we investigated the effects of DJB in diet-induced obese rats with NASH. Materials and methods: Male Wistar rats were divided into four groups and fed the following diets over 6 months: A) normal chow (NC group, n=6); B) methionine-choline-deficient (MCD)-high-fat (HF) diet (HF group, n=6); C) MCD-HF diet for 3 months followed by DJB and MCD-HF diet for subsequent 3 months (DJB group, n=6); and D) MCD-HF diet for 3 months followed by treatment with pioglitazone (PGZ) with MCD-HF diet for subsequent 3 months (PGZ group, n=6)...
2019: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Alina Constantin, Mădălina Dumitrescu, Miruna Nemecz, Ariana Picu, Bogdan Smeu, Cristian Guja, Nicoleta Alexandru, Adriana Georgescu, Gabriela Tanko
BACKGROUND: Pancreatic beta cells are highly sensitive to oxidative and endoplasmic reticulum (ER) stress, commonly occurring in type 2 diabetes (T2D) and obesity. OBJECTIVE: We aimed at investigating cellular responses of human beta cells exposed to sera from obese T2D patients treated differently, namely by conventional therapy or laparoscopic sleeve gastrectomy (LSG). METHODS: Serum samples from obese T2D men randomized to conventional treatment or LSG were taken at baseline and 6 months later...
January 30, 2019: Obesity Surgery
Ester Casanova, Josepa Salvadó, Anna Crescenti, Albert Gibert-Ramos
Obesity is associated with the hypertrophy and hyperplasia of adipose tissue, affecting the healthy secretion profile of pro- and anti-inflammatory adipokines. Increased influx of fatty acids and inflammatory adipokines from adipose tissue can induce muscle oxidative stress and inflammation and negatively regulate myocyte metabolism. Muscle has emerged as an important mediator of homeostatic control through the consumption of energy substrates, as well as governing systemic signaling networks. In muscle, obesity is related to decreased glucose uptake, deregulation of lipid metabolism, and mitochondrial dysfunction...
January 27, 2019: International Journal of Molecular Sciences
Men Su, Kambiz Naderi, Nathalie Samson, Ihsen Youssef, Livia Fülöp, Zsolt Bozso, Serge Laroche, Benoit Delatour, Sabrina Davis
Current evidence suggests dementia and pathology in Alzheimer's Disease (AD) are both dependent and independent of amyloid processing and can be induced by multiple 'hits' on vital neuronal functions. Type 2 diabetes (T2D) poses the most important risk factor for developing AD after ageing and dysfunctional IR/PI3K/Akt signalling is a major contributor in both diseases. We developed a model of T2D, coupling subdiabetogenic doses of streptozotocin (STZ) with a human junk food (HJF) diet to more closely mimic the human condition...
January 25, 2019: Molecular Neurobiology
Mei-Ying Zhang, Li-Yuan Wang, Shuang Zhao, Xiao-Chong Guo, Ying-Qi Xu, Zhi-Hong Zheng, Hang Lu, Hua-Chuan Zheng
Beclin 1 is involved in autophagy, differentiation, apoptosis and cancer progression, and functions as a haploinsufficient tumor suppressor gene. The aim of the present study was to elucidate the function of Beclin 1 in colon cancer. A Beclin 1-expressing plasmid was transfected into HCT-15 and HCT-116 cells, and the phenotypes and associated molecules were determined. Beclin 1 transfectants were subcutaneously injected into nude mice to determine tumor growth, and proliferation and apoptosis levels using Ki-67 immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), respectively...
February 2019: Oncology Letters
Kristina Wardelmann, Sabine Blümel, Michaela Rath, Eugenia Alfine, Chantal Chudoba, Mareike Schell, Weikang Cai, Robert Hauffe, Kathrin Warnke, Tanina Flore, Katrin Ritter, Jürgen Weiß, C Ronald Kahn, André Kleinridders
OBJECTIVE: Insulin action in the brain controls metabolism and brain function, which is linked to proper mitochondrial function. Conversely, brain insulin resistance associates with mitochondrial stress and metabolic and neurodegenerative diseases. In the present study, we aimed to decipher the impact of hypothalamic insulin action on mitochondrial stress responses, function and metabolism. METHODS: To investigate the crosstalk of insulin action and mitochondrial stress responses (MSR), namely the mitochondrial unfolded protein response (UPRmt) and integrated stress response (ISR), qPCR, western blotting, and mitochondrial activity assays were performed...
January 6, 2019: Molecular Metabolism
Risheng Ye, Toshiharu Onodera, Pierre-Gilles Blanchard, Christine M Kusminski, Victoria Esser, Rolf A Brekken, Philipp E Scherer
Syntrophins are a family of proteins forming membrane-anchored scaffolds and serving as adaptors for various transmembrane and intracellular signaling molecules. To understand the physiological roles of β1 syntrophin, one of the least characterized members, we generated mouse models to eliminate β1 syntrophin specifically in the endocrine or exocrine pancreas. β1 syntrophin is dispensable for the morphology and function of insulin-producing β-cells. However, mice with β1 syntrophin deletion in exocrine acinar cells exhibit increased severity of cerulein-induced acute pancreatitis...
January 14, 2019: American Journal of Pathology
Jan Martel, David M Ojcius, Yun-Fei Ko, Chih-Jung Chang, John D Young
Aging is influenced by many lifestyle choices that are under human control, including nutrition and exercise. The most effective known antiaging intervention consists of calorie restriction (CR), which increases lifespan in yeasts, worms, fruit flies, mice, and nonhuman primates. CR also improves healthspan by preventing the development of various aging-related diseases such as cancer, cardiovascular disease, diabetes, and neurodegeneration. Many compounds isolated from plants and fungi prolong lifespan and prevent age-related diseases in model organisms...
January 15, 2019: Medicinal Research Reviews
Senthilraja Selvam, Anand Ramaian Santhaseela, Dhasarathan Ganesan, Sudarshana Rajasekaran, Tamilselvan Jayavelu
Biotin is an indispensable adipogenic agent, and its ability to coordinate carbohydrate, lipid, and amino acid metabolism sensitizes insulin signaling in adipocytes. This enables the organism to adapt and survive under nutrient stress by synthesis and storage of lipids. Biotin deficiency mimics insulin resistance with alterations in cellular intermediary metabolism. Though the mechanism of lipogenesis is well established across cell types, considering its predisposition to accumulate only lipids, it is necessary to elucidate the mechanism that minimizes the effects of biotin on adipocyte protein synthesis...
January 15, 2019: Cell Stress & Chaperones
Biao Zhu, Yixiang Li, Lingwei Xiang, Jiajia Zhang, Li Wang, Bei Guo, Minglu Liang, Long Chen, Lin Xiang, Jing Dong, Min Liu, Wen Mei, Huan Li, Guangda Xiang
Alogliptin is a commonly prescribed drug treating patients with type 2 diabetes. Here, we show that long-term intervention with alogliptin (0.03% w/w in diet) improves survival and health of mice on a high-fat diet. Alogliptin intervention takes beneficial effects associated with longevity, including increased insulin sensitivity, attenuated functionality decline, decreased organ pathology, preserved mitochondrial function, and reduced oxidative stress. Autophagy activation is proposed as an underlying mechanism of these beneficial effects...
January 15, 2019: Aging Cell
Shingo Ito, Gentaro Honda, Yu Fujino, Seiryo Ogata, Mio Hirayama-Kurogi, Sumio Ohtsuki
PURPOSE: The aim of this work is to investigate the roles of solute carrier family 22 member 18 (SLC22A18) in lipid metabolism and in establishing the tumor phenotype of HepG2 cells. METHODS: SLC22A18-knockdown HepG2 cells were established by stable transfection with shRNA. Protein expression levels were measured by quantitative proteomics and Western blot analysis. Cell growth was examined by cell counting kit. Accumulation of triglyceride-rich lipid droplets was measured by Oil-Red O staining...
January 11, 2019: Pharmaceutical Research
Min Liu, Xiaojing Li, Si Ha, Anping Wang, Shinan Yin, Yiming Mu
OBJECTIVE: We aim to investigate whether C21, a selective angiotensin type 2 receptor agonist, can exert protective effects on pancreatic β-cells through activation of antiapoptosis and autophagy. METHODS: The high-fat diet-induced obese rats (HFDs) were under C21 treatment for 4 weeks. RESULTS: C21 treatment decreased the fasting glucose levels and improved β-cell insulin secretory function in the HFD group. Hematoxylin and eosin staining and electron microscopy indicated that the islet morphology was improved in the C21-treated obese rats, which was associated with increased levels of the key transcription factor PDX1, glucose sensing, and uptaking protein GCK and GLUT2, respectively...
February 2019: Pancreas
Stacey N Keenan, Ruth C Meex, Jennifer C Y Lo, Andrew Ryan, Shuai Nie, Magdalene K Montgomery, Matthew J Watt
Defects in hepatic lipid metabolism cause non-alcoholic fatty liver disease and insulin resistance, and these pathologies are closely linked. Regulation of lipid droplet metabolism is central to the control of intracellular fatty acid fluxes and perilipin (PLIN) 5 is important in this process. We examined the role of PLIN5 on hepatic lipid metabolism and systemic glycemic control using liver-specific Plin5 deficient mice ( Plin5 LKO ). Hepatocytes isolated from Plin5 LKO mice exhibited marked changes in lipid metabolism characterized by decreased fatty acid uptake and storage, decreased fatty acid oxidation that was associated with reduced contact between lipid droplets and mitochondria, and reduced triglyceride secretion...
January 7, 2019: Diabetes
Zhuang Juan, Jun Lu, Xin Wang, Xinfeng Wang, Weicheng Hu, Fashui Hong, Xiang-Xiang Zhao, Yuan-Lin Zheng
Prevention of obesity-induced cognitive decline is an important public health goal. Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, has beneficial potentials including antioxidant and neuroprotective activity. Evidence shows that anthocyanins can activate AMP-activated protein kinase (AMPK), a critical mediator of autophagy induction. This study investigated whether PSPC could improve cognitive function through regulating AMPK/autophagy signaling in HFD-fed obese mice. Our results showed that PSPC significantly ameliorated obesity, peripheral insulin resistance and memory impairment in HFD-fed mice...
November 12, 2018: Journal of Nutritional Biochemistry
Helena C Kenny, E Dale Abel
Patients with diabetes mellitus have >2× the risk for developing heart failure (HF; HF with reduced ejection fraction and HF with preserved ejection fraction). Cardiovascular outcomes, hospitalization, and prognosis are worse for patients with diabetes mellitus relative to those without. Beyond the structural and functional changes that characterize diabetic cardiomyopathy, a complex underlying, and interrelated pathophysiology exists. Despite the success of many commonly used antihyperglycemic therapies to lower hyperglycemia in type 2 diabetes mellitus the high prevalence of HF persists...
January 4, 2019: Circulation Research
Nan Wu, Dong Yang, Zhenchao Wu, Mengdie Yan, Pengju Zhang, Yi Liu
Recent clinical researches demonstrated "obesity paradox" in chronic obstructive pulmonary disease (COPD) patients. However, why obesity is beneficial to COPD development remains unclear. Obesity is distinguished by hyperinsulinemia, and cellular senescence of airway epithelial cells (AEC) is involved in COPD progression. In this study, we aim to investigate the roles of insulin in high concentration in AEC cellular senescence. Human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (HSAEpiC) were used for experiments and treated with insulin in indicated time period and concentration with or without 1% cigarette smoke extract (CSE) exposure, and autophagy activator (rapamycin) or inhibitor (chloroquine) after exposed to 1% CSE...
December 27, 2018: Biochemical and Biophysical Research Communications
Xiong Chen, Tingting Huang, Yujuan Shi, Luyin Wang, Wei Li, Feixia Shen, Xuemei Gu
Type 2 diabetes mellitus (T2DM) is characterized by the dysfunction and loss of pancreatic islet β‑cells, in part due to islet amyloid deposits derived from islet amyloid polypeptide (IAPP). The glucagon‑like peptide‑1 (GLP‑1) receptor agonist exendin‑4 enhances the insulin secretory response by increasing β‑cell mass in T2DM. However, it is unknown whether exendin‑4 protects β‑cells from IAPP‑mediated autophagy and apoptosis. In the present study, reverse transcription‑quantitative polymerase chain reaction, ELISA and western blotting were used to detected the mRNA and protein expression of insulin/hIAPP and other signaling molecules, while the mechanisms underlying these effects were also determined...
December 11, 2018: Molecular Medicine Reports
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