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Hui Yan, Wangbao Yang, Fenghua Zhou, Xiaopeng Li, Quan Pan, Zheng Shen, Guichun Han, Annie Newell-Fugate, Yanan Tian, Ravikumar Majeti, Wenshe Liu, Yong Xu, Chaodong Wu, Kimberly Allred, Clinton Allred, Yuxiang Sun, Shaodong Guo
Premenopausal women exhibit enhanced insulin sensitivity and reduced incidence of type 2 diabetes mellitus (T2D) compared with age-matched men, but this advantage disappears after menopause with disrupted glucose homeostasis, in part owing to a reduction in circulating 17β-estradiol (E2 ). Fasting hyperglycemia is a hallmark of T2D derived largely from dysregulation of hepatic glucose production (HGP), in which Foxo1 plays a central role in the regulation of gluconeogenesis. Here, we investigated the action of E2 on glucose homeostasis in male and ovariectomized (OVX) female control and liver-specific Foxo1 knockout (L-F1KO) mice, and sought to understand the mechanism by which E2 regulates gluconeogenesis via an interaction with hepatic Foxo1...
November 28, 2018: Diabetes
Leif-Christopher Engel, Ulf Landmesser, Alexander Goehler, Kevin Gigengack, Thomas Wurster, Costantina Manes, Georg Girke, Milosz Jaguszewski, Carsten Skurk, David M Leistner, Alexander Lauten, Andreas Schuster, Michel Noutsias, Bernd Hamm, Rene M Botnar, Boris Bigalke, Marcus R Makowski
The aim of this study was to compare endothelial permeability, which is considered a hallmark of CAD, between patients with different HbA1c-levels using an albumin-binding-MR-probe. This cross-sectional-study included 26 patients with clinical indication for x-ray-angiography, which were classified into 3 groups according to their HbA1c-levels (HbA1c<5.7%,<39mmol/mol; HbA1c=5.7-6.4%,39-47mmol/mol; HbA1c≥6.5%,48mmol/mol). Subjects underwent gadofosveset-enhanced-coronary-magnetic-resonance and x-ray-angiography including optical-coherence-tomography (OCT) within 24hours...
November 28, 2018: Diabetes
Samuela Pollack, Robert P Igo, Richard A Jensen, Mark Christiansen, Xiaohui Li, Ching-Yu Cheng, Maggie C Y Ng, Albert V Smith, Elizabeth J Rossin, Ayellet V Segrè, Samaneh Davoudi, Gavin S Tan, Yii-Der Ida Chen, Jane Z Kuo, Latchezar M Dimitrov, Lynn K Stanwyck, Weihua Meng, S Mohsen Hosseini, Minako Imamura, Darryl Nousome, Jihye Kim, Yang Hai, Yucheng Jia, Jeeyun Ahn, Aaron Leong, Kaanan Shah, Kyu Hyung Park, Xiuqing Guo, Eli Ipp, Kent D Taylor, Sharon G Adler, John R Sedor, Barry I Freedman, I-Te Lee, Wayne H-H Sheu, Michiaki Kubo, Atsushi Takahashi, Samy Hadjadj, Michel Marre, David-Alexandre Tregouet, Roberta Mckean-Cowdin, Rohit Varma, Mark I McCarthy, Leif Groop, Emma Ahlqvist, Valeriya Lyssenko, Elisabet Agardh, Andrew Morris, Alex S F Doney, Helen M Colhoun, Iiro Toppila, Niina Sandholm, Per-Henrik Groop, Shiro Maeda, Craig L Hanis, Alan Penman, Ching J Chen, Heather Hancock, Paul Mitchell, Jamie E Craig, Emily Y Chew, Andrew D Paterson, Michael A Grassi, Colin Palmer, Donald W Bowden, Brian L Yaspan, David Siscovick, Mary Frances Cotch, Jie Jin Wang, Kathryn P Burdon, Tien Y Wong, Barbara E K Klein, Ronald Klein, Jerome I Rotter, Sudha K Iyengar, Alkes Price, Lucia Sobrin
To identify genetic variants associated with diabetic retinopathy (DR), we performed a large, multiethnic genome-wide association study (GWAS). Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value < 1 X 10-5 were investigated in replication cohorts that included 18,545 Europeans, 16,453 Asians and 2,710 Hispanics...
November 28, 2018: Diabetes
Dorela D Shuboni-Mulligan, Maciej Parys, Barbara Blanco-Fernandez, Christiane L Mallett, Regina Schnegelberger, Marilia Takada, Shatadru Chakravarty, Bruno Hagenbuch, Erik M Shapiro
Diabetes mellitus is associated with hepatic metabolic dysfunction predisposing patients to drug induced liver injury. Mouse models of Type 2 diabetes (T2D) have dramatically reduced expression of Organic Anion Transporting Polypeptide (OATP) 1A1, a transporter expressed in hepatocytes and in the kidneys. Effects of diabetes on OATP1B2 expression are less studied and less consistent. OATP1A1 and OATP1B2 both transport endogenous substrates such as bile acids and hormone-conjugates as well as numerous drugs including Gd-EOB-DTPA...
November 28, 2018: Diabetes
Xinmei Zhang, Dennis C Y Yeung, Michal Karpisek, David Stejskal, Zhi-Guang Zhou, Feng Liu, Rachel L C Wong, Wing-Sun Chow, Annette W K Tso, Karen S L Lam, Aimin Xu
No abstract text is available yet for this article.
November 19, 2018: Diabetes
Célia Bidu, Quentin Escoula, Sandrine Bellenger, Aymé Spor, Maxime Galan, Audrey Geissler, André Bouchot, Dominique Dardevet, Béatrice Morio-Liondor, Patrice D Cani, Laurent Lagrost, Michel Narce, Jérôme Bellenger
No abstract text is available yet for this article.
November 19, 2018: Diabetes
Héloïse Dalle, Marie Garcia, Bénédicte Antoine, Vanessa Boehm, Thi Thu Huong Do, Marion Buyse, Tatiana Ledent, Antonin Lamazière, Christophe Magnan, Catherine Postic, Raphaël George Denis, Serge Luquet, Bruno Fève, Marthe Moldes
Widely used for their anti-inflammatory and immunosuppressive properties, glucocorticoids are nonetheless responsible for the development of diabetes and lipodystrophy. Despite an increasing number of studies focused on adipocyte glucocorticoid receptor (GR), its precise role in the molecular mechanisms of these complications remains unclear. In keeping with this goal, we generated a conditional adipocyte specific murine model of GR invalidation (AdipoGR-KO mice). Interestingly, when submitted to a corticosterone treatment to mimic hypercorticism conditions, AdipoGR-KO mice exhibited an improved glucose tolerance and insulin sensitivity...
November 19, 2018: Diabetes
Qiuyue Kong, Nan Li, Hao Cheng, Xiaojin Zhang, Xiaofei Cao, Tao Qi, Leyang Dai, Zhihong Zhang, Xuan Chen, Chuanfu Li, Yuehua Li, Bin Xue, Lei Fang, Li Liu, Zhengnian Ding
Nonalcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease worldwide. Macrophage-mediated inflammation plays a critical role in NASH pathogenesis; however, optimum therapies for macrophage activation and NASH remain elusive. Heat shock protein 12A (HSPA12A) encodes a novel member of the HSP70 family. Here, we report that NASH patients showed increased hepatic HSPA12A expression and serum HSPA12A contents. Intriguingly, knockout of HSPA12A ( Hspa12a -/- ) in mice attenuated high-fat diet (HFD)-induced hepatic steatosis and injury...
November 19, 2018: Diabetes
Andrew R Pepper, Antonio Bruni, Rena Pawlick, Doug O'Gorman, Tatsuya Kin, Aducio Thiesen, A M James Shapiro
The paucity of human donors confines the broadened application of β-cell replacement therapy. Insulin-producing cells derived from human embryonic stem cells (hESC), have been recently investigated clinically as a feasible surrogate to primary tissue. Herein, we examine the long-term efficacy of hESC derived pancreatic endoderm cells (PEC) to maintain normoglycemia post-transplant and characterize graft's phenotype.Chemically induced diabetic mice were transplanted with PEC into the subcutaneous device-less site...
November 19, 2018: Diabetes
Scott G Frodsham, Zhe Yu, Ann M Lyons, Adhish Agarwal, Melissa H Pezzolesi, Li Dong, Titte R Srinivas, Jian Ying, Tom Greene, Kalani L Raphael, Ken R Smith, Marcus G Pezzolesi
Sustained and rapid loss of glomerular filtration rate (GFR) is the predominant clinical feature of diabetic kidney disease and a requisite for the development of end-stage renal disease. While GFR trajectories have been studied in several diabetic and non-diabetic cohorts, whether rapid renal decline clusters in diabetic families has not been examined. To determine this, we estimated GFR (eGFR) from serum creatinine measurements obtained from 15,612 patients with diabetes at the University of Utah Health Sciences Center and established their renal function trajectories...
November 13, 2018: Diabetes
Francis M Hughes, Nathan A Hirshman, Brian M Inouye, Huixia Jin, Eloise W Stanton, Chloe E Yun, Leah G Davis, Jonathan C Routh, J Todd Purves
The NLRP3 inflammasome senses diabetic metabolites and initiates inflammation implicated in diabetic complications and neurodegeneration. No studies have investigated NLRP3 in diabetic bladder dysfunction (DBD), despite a high clinical prevalence. In vitro , we found that numerous diabetic metabolites activate NLRP3 in primary urothelial cells. In vivo we demonstrate NLRP3 is activated in urothelia from a genetic Type 1 diabetic mouse (Akita) by week 15. We then bred a NLRP3-/- genotype into these mice and found this blocked bladder inflammation and cystometric markers of DBD...
November 13, 2018: Diabetes
Li Ding, Lingling Han, John Dube, Daniel D Billadeau
WASH is an endosomal protein belonging to the Wiskott-Aldrich syndrome protein superfamily that participates in endosomal receptor trafficking by facilitating tubule fission via activation of the ubiquitously expressed Arp2/3 complex. While several studies have begun to understand the functions of WASH in cells lines, the in vivo function of WASH has not been fully elucidated since total body deletion in mice leads to early embryonic lethality. To circumvent this problem, we have used a WASH conditional knockout mouse model to investigate the role of WASH in the pancreas...
November 13, 2018: Diabetes
Zhonglin Chai, Tieqiao Wu, Aozhi Dai, Pacific Huynh, Frank Koentgen, Guy Krippner, Shuting Ren, Mark E Cooper
Targeting Cell Division Autoantigen 1 (CDA1) is postulated to attenuate the profibrotic actions of transforming growth factor-β in diabetic nephropathy. This study has identified a regulatory protein for CDA1 and has then used genetic and pharmacological approaches to test in vivo if strategies to target this pathway would lead to reduced renal injury. A novel protein, named CDA1BP1, was identified as critical in regulating the profibrotic activity of CDA1. Genetic deletion of CDA1BP1 attenuated key parameters of renal fibrosis in diabetic mice...
November 13, 2018: Diabetes
Holly A Cyphert, Emily M Walker, Yan Hang, Sangeeta Dhawan, Rachana Haliyur, Lauren Bonatakis, Dana Avrahami, Marcela Brissova, Klaus H Kaestner, Anil Bhushan, Alvin C Powers, Roland Stein
The sustained expression of the MAFB transcription factor in human islet β cells represents a distinct difference to mouse. Moreover, mRNA expression of closely related and islet β cell-enriched MAFA does not peak in humans until after nine years in age. Here we show that the MAFA protein is also weakly produced within the juvenile human islet β cell population, and that MafB expression is postnatally restricted in mouse β cells by de novo DNA methylation. To obtain insight into how MAFB affects human β cells, we developed a mouse model to ectopically express MafB in adult mouse β cells using MafA transcriptional control sequences...
November 13, 2018: Diabetes
Tianyi Huang, Kimberly Glass, Oana A Zeleznik, Jae H Kang, Kerry L Ivey, Abhijeet R Sonawane, Brenda M Birmann, Craig P Hersh, Frank B Hu, Shelley S Tworoger
Numerous studies have investigated individual biomarkers in relation to risk of type 2 diabetes. However, few have considered the interconnectivity of these biomarkers in the etiology of diabetes as well as the potential changes in the biomarker correlation network during diabetes development. We conducted a secondary analysis of 27 plasma biomarkers representing glucose metabolism, inflammation, adipokines, endothelial dysfunction, insulin-like growth factor axis and iron store plus age and BMI at blood collection from an existing case-control study nested in the Nurses' Health Study, including 1,303 incident diabetes cases and 1,627 healthy women...
November 8, 2018: Diabetes
Jonas Maczewsky, Julia Kaiser, Anne Gresch, Felicia Gerst, Martina Düfer, Peter Krippeit-Drews, Gisela Drews
The Takeda-G-protein-receptor-5 (TGR5) mediates physiological actions of bile acids. Since it was shown that TGR5 is expressed in pancreatic tissue, a direct TGR5 activation in beta-cells is currently postulated and discussed. The present study reveals that oleanolic acid (OLA) affects murine beta-cell function by TGR5 activation. Both, a Gαs inhibitor and an inhibitor of adenylyl cyclase (AC) prevented stimulating effects of OLA. Accordingly, OLA augmented the intracellular cAMP concentration. OLA and two well-established TGR5 agonists, RG239 and tauroursodeoxycholic acid (TUDCA), acutely promoted stimulus-secretion coupling (SSC)...
November 8, 2018: Diabetes
Rachel G Miller, Tina Costacou, Trevor J Orchard
In a recent Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) report, mean HbA1c was the strongest predictor of cardiovascular disease (CVD) after age. In DCCT/EDIC, mean diabetes duration was 6 (median 4) years at baseline and those with high blood pressure or cholesterol were excluded. We now replicate these analyses in the Pittsburgh Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset (<17 years) type 1 diabetes, with similar age (mean 27 years in both studies) but longer diabetes duration (mean 19, median 18 years) and no CVD risk factor exclusion at baseline...
November 8, 2018: Diabetes
Andrea V Haas, Bernard A Rosner, Raymond Y Kwong, Ajay D Rao, Rajesh Garg, Marcelo F Di Carli, Gail K Adler
Cardiovascular (CV) disease fatality rates are higher for women compared to men with diabetes despite lower rates of obstructive coronary artery disease (CAD). Impaired coronary flow reserve (CFR), the ratio of adenosine-stimulated to rest myocardial blood flow (MBF), is an indicator of coronary microvascular dysfunction and predicts major adverse CV events. We performed a post-hoc analysis to determine if there was a sex disparity in coronary microvascular dysfunction among 46 men and 27 women with well-controlled Type 2 DM and without clinical evidence of obstructive CAD...
November 8, 2018: Diabetes
Yang Jiao, Jiejie Zhao, Zhijian Zhang, Min Li, Xi Yu, Yanying Yang, Jie Liu, Shengjie Liao, Duanzhuo Li, Yuxing Wang, Die Zhang, Yulu Chen, Guojun Shi, Bin Liu, Yan Lu, Xiaoying Li
No abstract text is available yet for this article.
November 6, 2018: Diabetes
Clemens Wittenbecher, Meriem Ouni, Olga Kuxhaus, Markus Jähnert, Pascal Gottmann, Andrea Teichmann, Karina Meidtner, Jennifer Kriebel, Harald Grallert, Tobias Pischon, Heiner Boeing, Matthias B Schulze, Annette Schürmann
Recent studies suggest that insulin-like growth factor binding protein-2 (IGFBP-2) may protect against type 2 diabetes but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the IGFBP-2 gene with type 2 diabetes risk.Within the EPIC-Potsdam cohort (n=27,548), circulating IGFBP-2 concentration was assessed in a nested case-cohort (random subcohort, n=2500, all incident type 2 diabetes cases, n=820)...
November 5, 2018: Diabetes
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