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Shlomo Sasson
Activated peroxisome proliferator-activated receptor-δ (PPARδ) induces the expression of genes encoding enzymes that metabolize fatty acids and carbohydrate. Attempts to identify cellular activators of PPARδ produced large lists of various fatty acids and their metabolic derivatives; however, there is no consensus on specific and selective binding interactions of natural ligands with PPARδ. Most models on binding interactions within the ligand binding domain (LBD) of PPARδ have been derived from analyses of PPARδ-LBD crystals formed with synthetic low molecular weight ligands...
October 18, 2016: Biochimie
Christian Lehmann, Nicholas B Fisher, Barna Tugwell, Anna Szczesniak, Mel Kelly, Juan Zhou
BACKGROUND: Destruction of the insulin-producing beta cells in type 1 diabetes (T1D) is induced by invasion of immune cells causing pancreatic inflammation. Cannabidiol (CBD), a phytocannabinoid, derived from the plant, Cannabis sativa, was shown to lower the incidence of diabetes in non-obese diabetic (NOD) mice, an animal model of spontaneous T1D development. OBJECTIVE: The goal of this study was to investigate the impact of experimental CBD treatment on early pancreatic inflammation in T1D by intravital microscopy (IVM) in NOD mice...
October 18, 2016: Clinical Hemorheology and Microcirculation
Ingrid K Hals, Rinku Singh, Zuheng Ma, Hanne Scholz, Anneli Björklund, Valdemar Grill
We tested whether exposure of beta cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike...
October 20, 2016: Islets
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
Chrysovalantou Mihailidou, Ioulia Chatzistamou, Athanasios G Papavassiliou, Hippokratis Kiaris
Pancreatic dysfunction during diabetes is linked to the induction of endoplasmic reticulum (ER) stress on pancreatic beta (β) cells. Our laboratory recently discovered that p21 protects from diabetes by modifying the outcome of ER stress response. In the present study, we explored the antidiabetic activity of ciclopirox (CPX), an iron chelator and recently described activator of p21 expression. The effects of CPX in beta cell survival and function were assessed in cultured islets in vitro as well as in diabetic mice in vivo...
October 19, 2016: Pflügers Archiv: European Journal of Physiology
Mohammad Massumi, Farzaneh Pourasgari, Amarnadh Nalla, Battsetseg Batchuluun, Kristina Nagy, Eric Neely, Rida Gull, Andras Nagy, Michael B Wheeler
The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems...
2016: PloS One
Kristen E Syring, Kayla A Boortz, James K Oeser, Alessandro Ustione, Kenneth A Platt, Melanie K Shadoan, Owen P McGuinness, David W Piston, David R Powell, Richard M O'Brien
Polymorphisms in the SLC30A8 gene, which encodes the ZnT8 zinc transporter, are associated with altered susceptibility to type 2 diabetes (T2D) and SLC30A8 haploinsufficiency is protective against the development of T2D in obese humans. SLC30A8 is predominantly expressed in pancreatic islet beta cells but surprisingly multiple knockout mouse studies have shown little effect of Slc30a8 deletion on glucose tolerance or glucose-stimulated insulin secretion (GSIS). Multiple other Slc30a isoforms are expressed at low levels in pancreatic islets...
October 18, 2016: Endocrinology
Christian Ott, Iris Kistner, Axel Schmid, Stefanie Friedrich, Tilmann Ditting, Roland Veelken, Felix Mahfoud, Michael Böhm, Michael Uder, Roland Schmieder
OBJECTIVE: Renal denervation (RDN) lowers blood pressure (BP) by interruption of sympathetic nerve activity. A high sympathetic tone increases not only BP but also decreases pancreatic beta cell insulin secretion. Hence, the objective of the study was to analyze whether RDN improves secretory capacity of beta cells. DESIGN AND METHOD: In 40 patients (7 diabetics, 19 prediabetics, 14 non diabetics) with treatment resistant hypertension (defined by office BP ≥ 140/90 mmHg and diagnosis confirmed with 24-h ambulatory BP ≥ 130/80 mmHg), insulin secretion was measured before and 6 months after RDN (Simplicity flex catheter, Medtronic) by glucagon test...
September 2016: Journal of Hypertension
Gregory C Jones, Christopher A R Sainsbury
Cystic fibrosis is a common genetic condition and abnormal glucose handling leading to cystic fibrosis-related diabetes (CFRD) is a frequent comorbidity. CFRD is mainly thought to be the result of progressive pancreatic damage resulting in beta cell dysfunction and loss of insulin secretion. Whilst Oral Glucose Tolerance Testing is still recommended for diagnosing CFRD, the relationship between glucose abnormalities and adverse outcomes in CF is complex and occurs at stages of dysglycaemia occurring prior to diagnosis of diabetes by World Health Organisation criteria...
October 17, 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Dodanim Talavera-Adame, Orison O Woolcott, Joseph Ignatius-Irudayam, Vaithilingaraja Arumugaswami, David H Geller, Donald C Dafoe
No abstract text is available yet for this article.
October 17, 2016: Diabetologia
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
Soumen Bera, Sanjay Lamba, Mubasher Rashid, Anuj K Sharma, Alexander B Medvinsky, Claudia Acquisti, Amit Chakraborty, Bai-Lian Li
Impaired glutamate dehydrogenase (GDH) sensitivity to its inhibitors causes excessive insulin secretion by pancreatic beta-cells and defective ammonia metabolism in the liver. These symptoms are commonly associated with hyperinsulinism/hyperammonemia syndrome (HI/HA), which causes recurrent hypoglycaemia in early infancy. Hepatic localization of GDH amination and deamination activities linked with the urea cycle is known to be involved in ammonia metabolism and detoxification. Although deamination activities of hepatic GDH in the periportal zones of liver lobules and its connection to the urea cycle have been exhaustively investigated, physiological roles of GDH amination activity observed at pericentral zones have often been overlooked...
October 17, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Tinashe Chikowore, Tertia van Zyl, Edith J M Feskens, Karin R Conradie
AIMS: To determine the predictive utility of polygenic risk scores of common variants associated with type 2 diabetes derived from the European and Asian ethnicities among a black South African population. METHOD: Our study was a case-control study nested within the Prospective Urban and Rural Epidemiological (PURE) study of 178 male and female cases, matched for age and gender with 178 controls. Four types of genetic risk scores (GRS) were developed from 66 selected SNPs...
October 1, 2016: Diabetes Research and Clinical Practice
Rahul Krishnan, David Ko, Clarence E Foster, Wendy Liu, A M Smink, Bart de Haan, Paul De Vos, Jonathan R T Lakey
Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves...
2017: Methods in Molecular Biology
Fabio Arturo Grieco, Guido Sebastiani, Jonas Juan-Mateu, Olatz Villate, Laura Marroqui, Laurence Ladrière, Ksenya Tugay, Romano Regazzi, Marco Bugliani, Piero Marchetti, Francesco Dotta, Décio L Eizirik
Type 1 Diabetes is an autoimmune disease leading to beta cell destruction. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to beta cell death in T1D and their target genes remain to be clarified.We performed a miRNA expression profile on human islet preparations exposed to the cytokines IL-1β+IFN-γ. Confirmation of miRNAs and target genes modification in human beta cells was performed by real-time qPCR...
October 13, 2016: Diabetes
Ping Fang, Jingcheng Dong, Fangfang Zeng, Zihui Tang
BACKGROUND: The purpose of this study was to investigate the severity of glucose profiles and beta cell function associated with diabetic cardiovascular autonomic neuropathy (DCAN) in a Chinese sample. METHOD: A community-based, cross-sectional study to analyze the risk factors of DCAN was conducted with 455 individuals recruited from a Chinese population. Glucose profile risk score (GRS) was calculated to identify the association between the severity of the glucose profiles and DCAN...
October 13, 2016: Journal of Diabetes Investigation
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
M Incani, C Serafini, C Satta, L Perra, F Scano, P Frongia, R Ricciardi, C Ripoli, M Soro, A Strazzera, S Zampetti, R Buzzetti, M G Cavallo, E Cossu, M G Baroni
BACKGROUND: The incidence of T1DM In Sardinia is among the highest in the world (44.8 cases/100,000 person-years). Recommendations of the Immunology of Diabetes Society (IDS) advise evaluating autoantibody positivity in first-degree relatives (FDR) of patients with T1DM, for their higher risk to develop the disease. The aim of this study is to determine the prevalence of beta-cell autoimmunity in first-degree relatives of T1DM patients in Sardinia. METHODS: 188 Sardinian families were recruited in collaboration between Diabetes and Paediatric Units of University and District Hospitals in Sardinia...
October 11, 2016: Diabetes/metabolism Research and Reviews
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
Rehab Mohmed El-Gharbawy, Ashraf Mahmoud Emara, Sally El-Sayed Abu-Risha
The aim of this study was to use Zinc oxide nanoparticles and a standard antidiabetic drug to restore the function and structure of beta cells in a rat model of Type-2 diabetes and compare the effects of a DPP-IV inhibitor with or without zinc oxide nanoparticles (ZnONPs) using a model of type 2 diabetes (rats fed a high fat diet that was treated with a low dose of streptozotocin). Ninety male Wistar rats were randomly divided into three groups 10days after the induction of diabetes: group I: non-diabetic animals that received only the chow diet plus 2ml of 0...
October 7, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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