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Beta cell mass

Attilio Pingitore, Edward S Chambers, Thomas Hill, Inmaculada Ruz Maldonado, Bo Liu, Gavin Bewick, Douglas J Morrison, Tom Preston, Gareth A Wallis, Catriona Tedford, Ramón Castañera González, Guo Cai Huang, Pratik Choudhary, Gary Frost, Shanta J Persaud
AIMS: Diet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro. MATERIALS AND METHODS: For 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon...
October 20, 2016: Diabetes, Obesity & Metabolism
Roma Patel, Mitesh Dwivedi, Mohmmad Shoab Mansuri, Ansarullah, Naresh C Laddha, Ami Thakker, A V Ramachandran, Rasheedunnisa Begum
BACKGROUND: Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). OBJECTIVES: The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels...
2016: PloS One
Yue J Wang, Maria L Golson, Jonathan Schug, Daniel Traum, Chengyang Liu, Kumar Vivek, Craig Dorrell, Ali Naji, Alvin C Powers, Kyong-Mi Chang, Markus Grompe, Klaus H Kaestner
The human endocrine pancreas consists of multiple cell types and plays a critical role in glucose homeostasis. Here, we apply mass cytometry technology to measure all major islet hormones, proliferative markers, and readouts of signaling pathways involved in proliferation at single-cell resolution. Using this innovative technology, we simultaneously examined baseline proliferation levels of all endocrine cell types from birth through adulthood, as well as in response to the mitogen harmine. High-dimensional analysis of our marker protein expression revealed three major clusters of beta cells within individuals...
October 11, 2016: Cell Metabolism
Xiaosheng Xu, Jian Shen
Reduced placental growth factor (PLGF) during pregnancy is known to be a reason for developing preeclampsia (PE) and gestational diabetes mellitus (GDM), but the underlying mechanisms remain unclear. Recently, it has been shown that reduced PLGF may induce GDM through suppressing beta-cell mass growth in a PI3k/Akt signalling-dependent manner. Here, we dissected the interaction between beta-cells and islet endothelial cells in this model. We analysed proliferation of beta-cells and islet endothelial cells at different time points of gestation in mice...
2016: American Journal of Translational Research
Martina Pigoni, Johanna Wanngren, Peer-Hendrik Kuhn, Kathryn M Munro, Jenny M Gunnersen, Hiroshi Takeshima, Regina Feederle, Iryna Voytyuk, Bart De Strooper, Mikail D Levasseur, Brian J Hrupka, Stephan A Müller, Stefan F Lichtenthaler
BACKGROUND: The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer's disease. However, BACE1 therapeutic inhibition may cause unwanted adverse effects due to its additional functions in the nervous system, such as in myelination and neuronal connectivity. Additionally, recent proteomic studies investigating BACE1 inhibition in cell lines and cultured murine neurons identified a wider range of neuronal membrane proteins as potential BACE1 substrates, including seizure protein 6 (SEZ6) and its homolog SEZ6L...
October 5, 2016: Molecular Neurodegeneration
Hyun Yoon, Dae Jung Jeon, Chang Eun Park, Hye Sook You, Ae Eun Moon
The purpose of this study is to look at these relationships in non-diabetic Korean adults. This study was based on data from the KNHANES V-1, which is representative of the population of Korea. A total of 5,492 participants (≥20 years in age) without type 1 or type 2 diabetes, assessed for serum 25-hydroxyvitamin D [25(OH)D], fasting blood glucose and insulin, as well as anthropometric variables, were included in the analyses. The key study results were as follows: First, vitamin D status [vitamin D deficient, 25(OH)D <25 nM; vitamin D insufficient, 25(OH)D ≥25, <50 nM; vitamin D sufficient, 25(OH)D ≥50 nM] was inversely associated with homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in model 2 (adjusted for age and gender) and 3 (further adjusted for smoking, alcohol drinking, regular exercise, systolic and diastolic blood pressure, waist circumference, and body mass index)...
September 2016: Journal of Clinical Biochemistry and Nutrition
S A Nusaibah, A Siti Nor Akmar, A S Idris, M Sariah, Z Mohamad Pauzi
Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies...
September 19, 2016: Plant Physiology and Biochemistry: PPB
Mahmoud El Azzouny, Melissa J Longacre, Israr-Ul H Ansari, Robert T Kennedy, Charles F Burant, Michael J MacDonald
OBJECTIVE: Glucose-stimulated insulin secretion in pancreatic beta cells requires metabolic signals including the generation of glucose-derived short chain acyl-CoAs in the cytosol from mitochondrially-derived metabolites. One concept of insulin secretion is that ATP citrate lyase generates short chain acyl-CoAs in the cytosol from mitochondrially-derived citrate. Of these, malonyl-CoA, is believed to be an important signal in insulin secretion. Malonyl-CoA is also a precursor for lipids...
October 2016: Molecular Metabolism
Michael John Patton, Stuart McCorrister, Chris Grant, Garrett Westmacott, Robert Fariss, Pingzhao Hu, Kaiqiong Zhao, Mary Blake, Bill Whitmire, Chunfu Yang, Harlan D Caldwell, Grant McClarty
: The chlamydial protease-like activity factor (CPAF) is hypothesized to be an important secreted virulence factor; however, challenges in denaturing its proteolytic activity have hampered attempts to identify its legitimate targets. Here, we use a genetic and proteomic approach to identify authentic CPAF targets. Human epithelial cells infected with CPAF-sufficient and CPAF-deficient chlamydiae were lysed using known CPAF-denaturing conditions. Their protein profiles were analyzed using isobaric mass tags and liquid chromatography-tandem mass spectrometry...
September 27, 2016: MBio
Camille Attané, Marie-Line Peyot, Roxane Lussier, Pegah Poursharifi, Shangang Zhao, Dongwei Zhang, Johane Morin, Marco Pineda, Shupei Wang, Olivier Dumortier, Neil B Ruderman, Grant A Mitchell, Brigitte Simons, S R Murthy Madiraju, Erik Joly, Marc Prentki
AIMS/HYPOTHESIS: To directly assess the role of beta cell lipolysis in insulin secretion and whole-body energy homeostasis, inducible beta cell-specific adipose triglyceride lipase (ATGL)-deficient (B-Atgl-KO) mice were studied under normal diet (ND) and high-fat diet (HFD) conditions. METHODS: Atgl (flox/flox) mice were cross-bred with Mip-Cre-ERT mice to generate Mip-Cre-ERT(/+);Atgl (flox/flox) mice. At 8 weeks of age, these mice were injected with tamoxifen to induce deletion of beta cell-specific Atgl (also known as Pnpla2), and the mice were fed an ND or HFD...
September 27, 2016: Diabetologia
Amanda J Stock, Anne Kasus-Jacobi, Jonathan D Wren, Virginie H Sjoelund, Glenn D Prestwich, H Anne Pereira
We previously showed an elevated expression of the neutrophil protein, cationic antimicrobial protein of 37kDa (CAP37), in brains of patients with Alzheimer's disease (AD), suggesting that CAP37 could be involved in AD pathogenesis. The first step in determining how CAP37 might contribute to AD pathogenesis was to identify the receptor through which it induces cell responses. To identify a putative receptor, we performed GAMMA analysis to determine genes that positively correlated with CAP37 in terms of expression...
2016: PloS One
Hye Seung Jung, Yu Mi Kang, Ho Seon Park, Byung Yong Ahn, Hakmo Lee, Min Joo Kim, Jin Young Jang, Sun-Whe Kim
Post-translational modification by bonding of small ubiquitin-like modifier (SUMO) peptides influences various cellular functions, and is regulated by SUMO-specific proteases (SENPs). Several proteins have been suggested to have diverse impact on insulin synthesis and secretion through SUMO modification in beta cells. However, the role of SUMO modification in beta cell mass has not been established. Here, we examined the changes in expression of Senp in INS1 cells and pancreatic islets under diabetes-relevant stress conditions and associated changes in beta cell mass...
September 20, 2016: Islets
Sayuan Liang, Karim Louchami, Hauke Kolster, Anna Jacobsen, Ying Zhang, Julian Thimm, Abdullah Sener, Joachim Thiem, Willy Malaisse, Tom Dresselaers, Uwe Himmelreich
The assessment of the β-cell mass in experimental models of diabetes and ultimately in patients is a hallmark to understand the relationship between reduced β-cell mass/function and the onset of diabetes. It has been shown before that the GLUT-2 transporter is highly expressed in both β-cells and hepatocytes and that D-mannoheptulose (DMH) has high uptake specificity for the GLUT-2 transporter. As 19-fluorine MRI has emerged as a new alternative method for MRI cell tracking because it provides potential non-invasive localization and quantification of labeled cells, the purpose of this project is to validate β-cell and pancreatic islet imaging by using fluorinated, GLUT-2 targeting mannoheptulose derivatives ((19) FMH) both in vivo and ex vivo...
September 14, 2016: Contrast Media & Molecular Imaging
Lina Zhang, Giacomo Lanzoni, Matteo Battarra, Luca Inverardi, Qibin Zhang
: The etiology of Type 1 Diabetes (T1D) remains elusive. Enzymatically isolated and cultured (EIC) islets cannot fully reflect the natural protein composition and disease process of in vivo islets, because of the stress from isolation procedures. In order to study islet protein composition in conditions close to the natural environment, we performed proteomic analysis of EIC islets, and laser capture microdissected (LCM) human islets and acinar tissue from fresh-frozen pancreas sections of three cadaveric donors...
September 13, 2016: Journal of Proteomics
Junping Wen, Ting Xue, Ying Huang, Xiaoyan Chen, Ying Xue, Wei Lin, Lizhen Zhang, Jin Yao, Huibin Huang, Jixing Liang, Liantao Li, Lixiang Lin, Lidan Shi, Liangchun Cai, Zhuangli Zhu, Gang Chen
BACKGROUND: Beta-cells in different stages have different function and capacity of proliferation, regenerative and apoptosis. We conducted this study to investigate whether there are changes in beta-cell phonotype in the development of diabetes to identify potential beta cell targets for preventing the progression of diabetes. METHODS: We conducted a cross-sectional study of pancreatic tissues obtained from 80 patients classified into three groups: 25 type2 diabetes, 25 impaired fasting glucose, and 30 non-diabetes...
September 10, 2016: Journal of Diabetes
Beenu Moza Jalali, Pawel Likszo, Dariusz J Skarzynski
Conceptus attachment is a time-sensitive process that requires a synchronized uterine environment created by molecular changes in the endometrium in response to ovarian hormones and conceptus signals. Porcine conceptuses undergo rapid elongation and differentiation, and secrete estrogens that serve as maternal-recognition-of-pregnancy signals during the peri-implantation period (Days 11-12). Pregnancy-induced proteomic changes in the porcine endometrium were measured during this period using two-dimensional differential gel electrophoresis of endometrial protein lysates from Day-12 pregnant versus non-pregnant animals (n = 4 each)...
September 2016: Molecular Reproduction and Development
Kathleen M Fleming, Jennifer C Pekar, Brian D Leskiw
RATIONALE: While much of the interest and application of beta-diketonate complexes has focused predominately on the condensed phases, we report on the prevalence of gas-phase ligand exchange reactions leading to the formation of novel species. METHODS: Gas-phase ligand exchange reactions of Mg(eeac)2 and Mg(tftm)2 complexes with Cu(acac)2 , Cu(tftm)2 , Cu(dbm)2 , and Cu(eeac)2 were investigated using a direct insertion electron impact triple quadrupole mass spectrometer...
November 30, 2016: Rapid Communications in Mass Spectrometry: RCM
Sung-Bae Lee, Hyeong-Geug Kim, Hyo-Seon Kim, Jin-Seok Lee, Hwi-Jin Im, Won-Yong Kim, Chang-Gue Son
Amomum xanthioides has been traditionally used to treat diverse digestive system disorders in the Asian countries. We investigated antihepatofibrotic effects of ethyl acetate fraction of Amomum xanthioides (EFAX). Liver fibrosis is induced by dimethylnitrosamine (DMN) injection (intraperitoneally, 10 mg/kg of DMN for 4 weeks to Sprague-Dawley rats). EFAX (25 or 50 mg/kg), silymarin (50 mg/kg), or distilled water was orally administered every day. The DMN injection drastically altered body and organ mass, serum biochemistry, and platelet count, while EFAX treatment significantly attenuated this alteration...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Maribel Bruno, Jeffrey Ross, Yue Ge
Hexavalent chromium (Cr (VI)) is an environmental human carcinogen which primarily targets lungs. Among a variety of toxic mechanisms, disruption of biological pathways via translational and post-translational modifications represents a key mechanism through which Cr (VI) induces cytotoxicity and carcinogenesis. To identify those disruptions which are altered in response to cytotoxic Cr (VI) exposures, we measured and compared cytotoxicity and changes in expression and phosphorylation status of 15 critical biochemical pathway regulators in human BEAS-2B cells exposed for 48h to a non-toxic concentration (0...
August 31, 2016: Toxicology Letters
Jie Fan, Wan-Xia Zhang, Yi-Song Rao, Jing-Ling Xue, Fei-Fei Wang, Li Zhang, You-E Yan
The present study aims to evaluate whether perinatal nicotine (NIC) exposure increases obesity susceptibility in adult male rat offspring by altering early adipogenesis. NIC was subcutaneously administered (2.0 mg/kg per day) to pregnant rats from gestational day 9 to the time of weaning (PND 28). At weaning, NIC-exposed male pups had an increased body weight (bw) and inguinal subcutaneous fat mass and a decreased average cell area of adipocyte, which was accompanied by an overexpression of adipogenic and lipogenic genes in the epididymal white adipose tissue (eWAT)...
September 2, 2016: Endocrinology
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