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https://www.readbyqxmd.com/read/28634592/euglycemic-diabetic-ketoacidosis-with-prolonged-glucosuria-associated-with-the-sodium-glucose-cotransporter-2-canagliflozin
#1
Daniel A Kelmenson, Kelsey Burr, Yusra Azhar, Paul Reynolds, Chelsea A Baker, Neda Rasouli
Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control by a reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. This unique mechanism, independent of insulin secretion and beta cell function, has made this class of medication desirable in patients with type 2 diabetes. However in May 2015, the US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors...
April 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28633420/pancreas-fat-and-beta-cell-mass-in-humans-with-and-without-diabetes-an-analysis-in-the-japanese-population
#2
Rie Murakami, Yoshifumi Saisho, Yuusuke Watanabe, Jun Inaishi, Tami Tsuchiya, Kinsei Kou, Seiji Sato, Minoru Kitago, Yuko Kitagawa, Taketo Yamada, Hiroshi Itoh
Context: The mechanisms by which beta cell mass is reduced in patients with type 2 diabetes (T2DM) remain unclear. It has been postulated that ectopic fat deposits in the pancreas induce beta cell apoptosis, leading to the development of diabetes. Objective: The aim of this study was to clarify the effects of intra-pancreatic fat on beta and alpha cell mass in humans with and without diabetes. Design, Subjects and Methods: Using our tissue database, pancreas sections of 72 Japanese non-diabetic (NDM) autopsy cases and 50 diabetic (DM) and 49 age- and BMI-matched NDM patients who underwent pancreatic surgery were analyzed...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#3
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28629856/ethnic-differences-in-glucose-effectiveness-and-disposition-index-in-overweight-obese-african-american-and-white-women-with-prediabetes-a-study-of-compensatory-mechanisms
#4
Kwame Osei, Trudy Gaillard
OBJECTIVE: Prediabetes, a major precursor of type 2 diabetes, varies among ethnic populations. Therefore, we compared the pathophysiologic mechanisms of prediabetes in overweight/obese African American (AA) and White American (WA) women. SUBJECTS AND METHODS: We recruited 95 women (67 AA, 28 WA) with prediabetes. Standard OGTT and FSIVGTT were performed in each subject. Insulin sensitivity (Si), glucose effectiveness (Sg), beta cell function (acute insulin response to glucose (AIRg) and disposition index (DI: Si×AIRg) were calculated using Bergman's Minmod...
March 14, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28628102/regulation-of-body-weight-and-energy-homeostasis-by-neuronal-cell-adhesion-molecule-1
#5
Thomas Rathjen, Xin Yan, Natalia L Kononenko, Min-Chi Ku, Kun Song, Leiron Ferrarese, Valentina Tarallo, Dmytro Puchkov, Gaga Kochlamazashvili, Sebastian Brachs, Luis Varela, Klara Szigeti-Buck, Chun-Xia Yi, Sonja C Schriever, Sudhir Gopal Tattikota, Anne Sophie Carlo, Mirko Moroni, Jan Siemens, Arnd Heuser, Louise van der Weyden, Andreas L Birkenfeld, Thoralf Niendorf, James F A Poulet, Tamas L Horvath, Matthias H Tschöp, Matthias Heinig, Mirko Trajkovski, Volker Haucke, Matthew N Poy
Susceptibility to obesity is linked to genes regulating neurotransmission, pancreatic beta-cell function and energy homeostasis. Genome-wide association studies have identified associations between body mass index and two loci near cell adhesion molecule 1 (CADM1) and cell adhesion molecule 2 (CADM2), which encode membrane proteins that mediate synaptic assembly. We found that these respective risk variants associate with increased CADM1 and CADM2 expression in the hypothalamus of human subjects. Expression of both genes was elevated in obese mice, and induction of Cadm1 in excitatory neurons facilitated weight gain while exacerbating energy expenditure...
June 19, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28626572/optical-control-of-a-receptor-linked-guanylyl-cyclase-using-a-photoswitchable-peptidic-hormone
#6
Tom Podewin, Johannes Broichhagen, Christina Frost, Dieter Groneberg, Julia Ast, Helena Meyer-Berg, Nicholas H F Fine, Andreas Friebe, Martin Zacharias, David J Hodson, Dirk Trauner, Anja Hoffmann-Röder
The optical control over biological function with small photoswitchable molecules has gathered significant attention in the last decade. Herein, we describe the design and synthesis of a small library of photoswitchable peptidomimetics based upon human atrial natriuretic peptide (ANP), in which the photochromic amino acid [3-(3-aminomethyl)phenylazo]phenylacetic acid (AMPP) is incorporated into the peptide backbone. The endogeneous hormone ANP signals via the natriuretic peptide receptor A (NPR-A) through raising intracellular cGMP concentrations, and is involved in blood pressure regulation and sodium homeostasis, as well as lipid metabolism and pancreatic function...
June 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28625830/bioengineering-strategies-for-inducing-tolerance-in-autoimmune-diabetes
#7
Steinunn Baekkeskov, Jeffrey A Hubbell, Edward A Phelps
Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets. Strategies to delay onset or prevent the autoimmune recognition of beta cell antigens or T cell-mediated killing of beta cells have mainly focused on systemic immunomodulation and antigen-specific immunotherapy. To bridge the fields of type 1 diabetes immunology and biomaterials engineering, this article will review recent trends in the etiology of type 1 diabetes immunopathology and will focus on the contributions of emerging bioengineered strategies in the fight against beta cell autoimmunity in type 1 diabetes...
June 15, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28625491/insulinotropic-action-of-2-4-dinitroanilino-benzoic-acid-through-the-attenuation-of-pancreatic-beta-cell-lesions-in-diabetic-rats
#8
Humera Jahan, M Iqbal Choudhary, Mehwish Manzoor, Khalid Mohammad Khan, Shahnaz Perveen, Atta-Ur Rahman
Beta cell destruction plays a key role in the pathogenesis of type 1 diabetes mellitus. It has also been argued that beta cell mass may also be compromised in some cases of type 2 diabetes, although this is controversial. Currently, the failure of oral antidiabetic insulin secretagogue drugs to properly correct type 2 diabetes demands novel approaches in the treatment of this condition. For any condition associated with diminished beta cell function, the aim of the present study was to investigate the in vitro and in vivo antidiabetic effect in STZ-induced diabetic rats, and maximum tolerated dose (MTD) safety of novel anthranilic acid derivative, 2, 4-dinitroanilino-benzoic acid (1)...
June 15, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28620237/lea29y-expression-in-transgenic-neonatal-porcine-islet-like-cluster-promotes-long-lasting-xenograft-survival-in-humanized-mice-without-immunosuppressive-therapy
#9
L Wolf-van Buerck, M Schuster, F S Oduncu, A Baehr, T Mayr, S Guethoff, J Abicht, B Reichart, N Klymiuk, E Wolf, J Seissler
Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice stably reconstituted with a human immune system...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28617859/co-localization-of-acinar-markers-and-insulin-in-pancreatic-cells-of-subjects-with-type-2-diabetes
#10
Matilde Masini, Lorella Marselli, Eddy Himpe, Luisa Martino, Marco Bugliani, Mara Suleiman, Ugo Boggi, Franco Filipponi, Margherita Occhipinti, Luc Bouwens, Vincenzo De Tata, Piero Marchetti
To search for clues suggesting that beta cells may generate by transdifferentiation in humans, we assessed the presence of cells double positive for exocrine (amylase, carboxypeptidase A) and endocrine (insulin) markers in the pancreas of non-diabetic individuals (ND) and patients with type 2 diabetes (T2D). Samples from twelve ND and twelve matched T2D multiorgan donors were studied by electron microscopy, including amylase and insulin immunogold labeling; carboxypeptidase A immunofluorescence light microscopy assessment was also performed...
2017: PloS One
https://www.readbyqxmd.com/read/28617856/the-associations-between-vdr-bsmi-polymorphisms-and-risk-of-vitamin-d-deficiency-obesity-and-insulin-resistance-in-adolescents-residing-in-a-tropical-country
#11
Rayinda Rahmadhani, Nur Lisa Zaharan, Zahurin Mohamed, Foong Ming Moy, Muhammad Yazid Jalaludin
BACKGROUND: The vitamin D receptor (VDR) gene is expressed abundantly in different tissues; including adipocytes and pancreatic beta cells. The rs1544410 or BsmI single nucleotide polymorphism (SNP) in the intronic region of the VDR gene has been previously associated with vitamin D levels, obesity and insulin resistance. AIMS: This study was aimed to examine the association between BsmI polymorphism and risk of vitamin D deficiency, obesity and insulin resistance in adolescents living in a tropical country...
2017: PloS One
https://www.readbyqxmd.com/read/28615694/selective-serotonin-reuptake-inhibitor-fluoxetine-impairs-e-cadherin-mediated-cell-adhesion-and-alters-calcium-homeostasis-in-pancreatic-beta-cells
#12
Huang-Yu Chang, Shu-Ling Chen, Meng-Ru Shen, Mei-Lang Kung, Lee-Ming Chuang, Yun-Wen Chen
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed drugs for mood disorders. Long term use of SSRIs is associated with an increased risk of diabetes, but the underlying mechanism(s) remains elusive. E-cadherin-mediated cell-cell adhesion and elevated [Ca(2+)]i are important for insulin release and pancreatic β cell functions. This study aims to investigate whether a SSRI, fluoxetine (Prozac), induces pancreatic β cell dysfunction through affecting E-cadherin and/or [Ca(2+)]i...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612706/autophagy-and-its-link-to-type-ii-diabetes-mellitus
#13
Jai-Sing Yang, Chi-Cheng Lu, Sheng-Chu Kuo, Yuan-Man Hsu, Shih-Chang Tsai, Shih-Yin Chen, Yng-Tay Chen, Ying-Ju Lin, Yu-Chuen Huang, Chao-Jung Chen, Wei-De Lin, Wen-Lin Liao, Wei-Yong Lin, Yu-Huei Liu, Jinn-Chyuan Sheu, Fuu-Jen Tsai
Autophagy, a double-edged sword for cell survival, is the research object on 2016 Nobel Prize in Physiology or Medicine. Autophagy is a molecular mechanism for maintaining cellular physiology and promoting survival. Defects in autophagy lead to the etiology of many diseases, including diabetes mellitus (DM), cancer, neurodegeneration, infection disease and aging. DM is a metabolic and chronic disorder and has a higher prevalence in the world as well as in Taiwan. The character of diabetes mellitus is hyperglycemia resulting from defects in insulin secretion, insulin action, or both...
June 2017: BioMedicine
https://www.readbyqxmd.com/read/28611037/inhibition-of-renal-sodium-glucose-co-transport-with-empagliflozin-lowers-fasting-plasma-glucose-and-improves-beta-cell-function-in-subjects-with-impaired-fasting-glucose
#14
Muhammad Abdul-Ghani, Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Curtis Triplitt, Ralph A DeFronzo
To examine the effect of renal sodium glucose co-transporter inhibition with empagliflozin on the fasting plasma glucose concentration and beta cell function in subjects with impaired fasting glucose (IFG).8 subjects with normal fasting glucose and 8 subjects with IFG received empagliflozin (25 mg/day) for 2 weeks. Fasting plasma glucose concentration and beta cell function was measured with a 9-step hyperglycemic clamp before and 48 hours and 14 days after the start of empagliflozin.Empagliflozin caused 50±4 and 45±4 grams glucosuria on day 2 in IFG and NFG subjects, respectively, and the glucosuria was maintained for 2 weeks in both groups...
June 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28609823/association-of-directly-measured-plasma-free-25-oh-d-with-insulin-sensitivity-and-secretion-%C3%A2-the-iras-family-study
#15
C. Christine Lee, Kendra A. Young, Jill M. Norris, Jerome I. Rotter, Yeheng Liu, Carlos Lorenzo, Lynne E. Wagenknecht, David E. Cole, Steven M. Haffner, Yii-Der I. Chen, Anthony J. Hanley
Objectives: We aimed to compare the associations of directly measured plasma free 25-hydroxyvitamin D [25(OH)D] and total 25(OH)D concentrations with insulin sensitivity and beta-cell function in non-diabetic Hispanics and African-Americans. We hypothesized that directly measured free 25(OH)D would be more strongly associated with these measures of glucose homeostasis and that associations would differ by race. Methods: We studied 1,189 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study, using data from baseline examinations in 2000–2002...
May 10, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28608700/a-chaotic-bursting-spiking-transition-in-a-pancreatic-beta-cells-system-observation-of-an-interior-glucose-induced-crisis
#16
Jorge Duarte, Cristina Januario, Nuno Martins
Nonlinear systems are commonly able to display abrupt qualitative changes (or transitions) in the dynamics. A particular type of these transitions occurs when the size of a chaotic attractor suddenly changes. In this article, we present such a transition through the observation of a chaotic interior crisis in the Deng bursting-spiking model for the glucose-induced electrical activity of pancreatic β-cells. To this chaos-chaos transition corresponds precisely the change between the bursting and spiking dynamics, which are central and key dynamical regimes that the Deng model is able to perform...
August 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/28605280/the-gut-a-key-to-the-pathogenesis-of-type-2-diabetes
#17
Jens Juul Holst, Jens Pedersen, Nicolai Jacob Wewer Albrechtsen, Filip Krag Knop
In this communication we discuss the role of the gut for the development of type 2 diabetes mellitus (T2DM). Gastric emptying rates importantly determine postprandial glucose excursions and regulate postprandial secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). It thereby also determines their powerful, amplifying effect on glucose-induced insulin secretion and thus the ability of the body to regulate glucose disposal. Although disturbances in gastric emptying are not consistent findings in type 2 diabetes, the incretin system is seriously impaired, probably associated with insulin resistance and obesity...
June 12, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28599824/the-clinical-characteristics-of-patients-with-mitochondrial-trna-leu-uur-m-3243a-g-mutation-compared-with-type-1-diabetes-and-early-onset-type-2-diabetes
#18
Jie Zhu, Peng Yang, Xiang Liu, Li Yan, Sharvan Rampersad, Feng Li, Hong Li, Chunjun Sheng, Xiaoyun Cheng, Manna Zhang, Shen Qu
OBJECTIVE: This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM). METHODS: The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m...
April 29, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28598424/raptor-regulates-functional-maturation-of-murine-beta-cells
#19
Qicheng Ni, Yanyun Gu, Yun Xie, Qinglei Yin, Hongli Zhang, Aifang Nie, Wenyi Li, Yanqiu Wang, Guang Ning, Weiqing Wang, Qidi Wang
Diabetes is associated with beta cell mass loss and islet dysfunctions. mTORC1 regulates beta cell survival, proliferation and function in physiological and pathological conditions, such as pregnancy and pancreatectomy. Here we show that deletion of Raptor, which is an essential component of mTORC1, in insulin-expressing cells promotes hypoinsulinemia and glucose intolerance. Raptor-deficient beta cells display reduced glucose responsiveness and exhibit a glucose metabolic profile resembling fetal beta cells...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28597969/the-role-of-epigenetic-regulation-and-pluripotency-related-micrornas-in-differentiation-of-pancreatic-stem-cells-to-beta-cells
#20
Ediz Coskun, Merve Ercin, Selda Gezginci-Oktayoglu
In this study, we aimed to research class-I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI-MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. The valproic acid, is an inhibitor of class I HDACs, caused the highest beta cell differentiation in PI-MSCs. However, the cells in this group were at early stages of differentiation. Glucose co-administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional...
June 9, 2017: Journal of Cellular Biochemistry
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