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https://www.readbyqxmd.com/read/28731364/synthesis-of-a-new-insulin-mimetic-anti-diabetic-drug-containing-vitamin-a-and-vanadium-iv-salt-chemico-biological-characterizations
#1
Abdel Majid A Adam, Ahmed M Naglah, Mohamed A Al-Omar, Moamen S Refat
Diabetes patients suffer from chronic disorders in the metabolism due to high blood sugar caused by anomalies in insulin excretion. Recently, vanadium compounds have been prepared and functionalized to decrease the level of hyperglycemia. Vitamin A boosts beta cell activity; therefore, the lack of this vitamin plays a role in the development of type 2 diabetes. The aim of this article focused on the synthesis of a new anti-diabetic drug formed from the complexation of a vanadium(IV) salt with vitamin A. Vitamin A acts as a unidentate chelate through the oxygen of its -OH group...
July 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28730907/the-rs10229583-polymorphism-near-paired-box-gene-4-is-associated-with-gestational-diabetes-mellitus-in-chinese-women
#2
Tianyi Xu, Yiru Shi, Jiangbo Liu, Yun Liu, Ailin Zhu, Cui Xie, Yan Zhang, Yan Chen, Lirong Ren
Objective The rs10229583 polymorphism near paired box gene 4 ( PAX4) is associated with insulin resistance and type 2 diabetes. Mutations in the PAX4 gene may be associated with impaired differentiation/development of pancreatic islet beta cells during fetal development and, consequently, a compromised insulin response to high blood glucose. To ascertain whether this polymorphism plays a role in gestational diabetes mellitus (GDM), we investigated the genotypic and allele frequency differences between GDM and normal pregnancies...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28730558/transplantation-sites-for-porcine-islets
#3
Rebecca A Stokes, Denbigh M Simond, Heather Burns, Anita T Patel, Philip J O'Connell, Jenny E Gunton, Wayne J Hawthorne
AIMS/HYPOTHESIS: Xenotransplantation has great potential to provide beta cell replacement and thereby provide a cure for large numbers of people with type 1 diabetes. Crucial to the success of xenotransplantation is establishment of the most viable sites for transplantation. METHODS: We compared porcine islet tissue transplanted into kidney, liver and spleen in pig recipients as assessed by blood glucose levels and IVGTT. RESULTS: Kidney was the superior site for porcine islet tissue transplantation, followed by liver then spleen...
July 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28728928/gtf-231-a-mixture-of-gymnemic-acid-trigonelline-and-ferulic-acid-significantly-ameliorates-oxidative-stress-in-experimental-type-2-diabetes-in-rats
#4
Roshana Devi Vellai, Sharmila Chandiran, Subramanian Sorimuthu Pillai
OBJECTIVES: According to a report by the United States National Health and Nutrition Examination Survey, nearly 60% of patients with diabetes have more than one complication caused by chronic diabetes. Type 2 diabetes is a multifactorial metabolic disorder that accounts for more than 95% of people with diabetes and usually requires multitargeted therapeutic interventions. It arises due to insufficient insulin secretion or its action or both. Recently, we reported that the oral administration of gymnemic acid, trigonelline and ferulic acid in the ratio of 2:3:1 (GTF-231), a mixture of 3 phytoingredients at a concentration of 300 mg/kg body weight significantly improved the glucose homeostasis in rats with low-dose streptozotocin-induced type 2 diabetes that were fed with high-fat diet...
July 17, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28728159/oxamate-enhances-the-anti-inflammatory-and-insulin-sensitizing-effects-of-metformin-in-diabetic-mice
#5
Mu-Chao Wu, Wei-Ran Ye, Yi-Jia Zheng, Shan-Shan Zhang
Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice...
July 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28727908/leveraging-a-clinical-phase-ib-proof-of-concept-study-for-the-gpr40-agonist-mk-8666-in-patients-with-type-2-diabetes-for-model-informed-phase-ii-dose-selection
#6
A W Krug, P Vaddady, R A Railkar, B J Musser, J Cote, Agh Ederveen, D G Krefetz, E DeNoia, A L Free, L Morrow, M V Chakravarthy, E Kauh, D A Tatosian, P A Kothare
GPR40 mediates free fatty acid-induced insulin secretion in beta cells. We investigated the safety, pharmacokinetics, and glucose response of MK-8666, a partial GPR40 agonist, after once-daily multiple dosing in type 2 diabetes patients. This double-blind, multisite, parallel-group study randomized 63 patients (placebo, n = 18; 50 mg, n = 9; 150 mg, n = 18; 500 mg, n = 18) for 14-day treatment. The results showed no serious adverse effects or treatment-related hypoglycemia. One patient (150-mg group) showed mild-to-moderate transaminitis at the end of dosing...
July 20, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28725915/ikk%C3%AE-inhibition-prevents-fat-induced-beta-cell-dysfunction-in-vitro-and-in-vivo-in-rodents
#7
Aleksandar Ivovic, Andrei I Oprescu, Khajag Koulajian, Yusaku Mori, Judith A Eversley, Liling Zhang, Rodolfo Nino-Fong, Gary F Lewis, Marc Y Donath, Michael Karin, Michael B Wheeler, Jan Ehses, Allen Volchuk, Catherine B Chan, Adria Giacca
AIMS/HYPOTHESIS: We have previously shown that oxidative stress plays a causal role in beta cell dysfunction induced by fat. Here, we address whether the proinflammatory kinase inhibitor of (nuclear factor) κB kinase β (IKKβ), which is activated by oxidative stress, is also implicated. METHODS: Fat (oleate or olive oil) was infused intravenously in Wistar rats for 48 h with or without the IKKβ inhibitor salicylate. Thereafter, beta cell function was evaluated in vivo using hyperglycaemic clamps or ex vivo in islets isolated from fat-treated rats...
July 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28724742/the-myokine-irisin-is-released-in-response-to-saturated-fatty-acids-and-promotes-pancreatic-beta-cell-survival-and-insulin-secretion
#8
Annalisa Natalicchio, Nicola Marrano, Giuseppina Biondi, Rosaria Spagnuolo, Rossella Labarbuta, Immacolata Porreca, Angelo Cignarelli, Marco Bugliani, Piero Marchetti, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
This study explored the role of irisin as a new pancreatic beta-cell secretagogue and survival factor and its potential role in the communication between skeletal muscle and pancreatic beta-cells under lipotoxic conditions. Recombinant irisin stimulated insulin biosynthesis and glucose-stimulated insulin secretion (GSIS) in a PKA-dependent manner, and prevented saturated fatty acid-induced apoptosis in human and rat pancreatic beta-cells, as well as in human and murine pancreatic islets, via AKT/BCL2 signaling...
July 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28721437/erk1-is-dispensable-for-mouse-pancreatic-beta-cell-function-but-is-necessary-for-glucose-induced-full-activation-of-msk1-and-creb
#9
Michele Leduc, Joy Richard, Safia Costes, Dany Muller, Annie Varrault, Vincent Compan, Julia Mathieu, Jean-François Tanti, Gilles Pagès, Jacques Pouyssegur, Gyslaine Bertrand, Stéphane Dalle, Magalie A Ravier
AIMS/HYPOTHESIS: Insufficient insulin secretion from pancreatic beta cells, which is associated with a decrease in beta cell mass, is a characteristic of type 2 diabetes. Extracellular signal-related kinase 1 and 2 (ERK1/2) inhibition in beta cells has been reported to affect insulin secretion, gene transcription and survival, although whether ERK1 and ERK2 play distinct roles is unknown. The aim of this study was to assess the individual roles of ERK1 and ERK2 in beta cells using ERK1 (also known as Mapk3)-knockout mice (Erk1 (-/-) mice) and pharmacological approaches...
July 18, 2017: Diabetologia
https://www.readbyqxmd.com/read/28720696/persistent-organic-pollutants-impair-insulin-secretory-function-of-pancreatic-beta-cells-human-and-in-vitro-evidence
#10
Yu-Mi Lee, Chae-Myeong Ha, Se-A Kim, Themis Thoudam, Young-Ran Yoon, Dae-Jung Kim, Hyeon-Chang Kim, Hyo-Bang Moon, Sungmi Park, In-Kyu Lee, Duk-Hee Lee
Persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), have emerged as a new risk factor of type 2 diabetes (T2D). We evaluated whether chronic exposure to low-dose POPs affects insulin secretory function of beta-cells in humans and in vitro cells. Serum concentrations of OCPs and PCBs were measured in 200 nondiabetic adults. Mathematical-model-based insulin secretion indices were estimated using a 2-hour 7-sample oral glucose tolerance test. Insulin secretion by INS1E beta-cells was measured after 48-hour treatment with 3 OCPs or a PCB mixture...
July 18, 2017: Diabetes
https://www.readbyqxmd.com/read/28720517/transient-receptor-potential-trpm3-channels-pharmacology-signaling-and-biological-functions
#11
REVIEW
Gerald Thiel, Sandra Rubil, Andrea Lesch, Lisbeth A Guethlein, Oliver G Rössler
The transient receptor potential melastatin-3 (TRPM3) channel belongs to the family of transient receptor potential (TRP) cation channels that are expressed in a variety of tissues and cell types, including dorsal root ganglia, cardiomyocytes and pancreatic beta-cells. Although its natural ligands are currently unknown, TRPM3 channels can be activated by the neurosteroid pregnenolone sulfate, the synthetic ligand CIM0216, and by noxious heat. TRPM3 channels are regulated by phosphoinositides, and perhaps by calmodulin...
July 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28720321/no-evidence-for-progressive-deterioration-in-stimulated-insulin-secretion-in-renal-transplant-recipients-after-12years-tacrolimus-exposure
#12
Mariëlle A C J Gelens, Johannes P van Hooff, Len Usvyat, Maarten H Christiaans
AIMS: Tacrolimus (Tac) inhibits insulin secretion in a Tac-trough blood level dependent way early post-transplant in renal transplant recipients (Rtx). It is unknown whether long-term exposure results into a progressive beta cells dysfunction. METHODS: Two independent cohorts of Tac-treated non-diabetic Rtx, previously participating in glucose metabolism studies using intravenous Glucose Tolerance Test (ivGTT) were included: Fifty-eight Rtx were tested by ivGTT cross-sectional between 0...
July 4, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28717166/targeting-cellular-calcium-homeostasis-to-prevent-cytokine-mediated-beta-cell-death
#13
Amy L Clark, Kohsuke Kanekura, Zeno Lavagnino, Larry D Spears, Damien Abreu, Jana Mahadevan, Takuya Yagi, Clay F Semenkovich, David W Piston, Fumihiko Urano
Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713332/childhood-maltreatment-is-an-independent-risk-factor-for-prediabetic-disturbances-in-glucose-regulation
#14
Li Li, W Timothy Garvey, Barbara A Gower
AIMS: Childhood maltreatment (CM) is shown to be associated with obesity and depression. However, the relationship of CM to prediabetic state is much less studied. We tested the hypothesis that CM increases the risk for prediabetic state due to glucose intolerance, reduced insulin sensitivity, and beta cell function. METHODS: Oral glucose tolerance test (OGTT)-derived metabolic parameters of glucose tolerance, insulin sensitivity, and beta cell function were measured in 121 participants aged 19-60 years...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28711973/piwi-interacting-rnas-as-novel-regulators-of-pancreatic-beta-cell-function
#15
Imène Sarah Henaoui, Cécile Jacovetti, Inês Guerra Mollet, Claudiane Guay, Jonathan Sobel, Lena Eliasson, Romano Regazzi
AIMS/HYPOTHESIS: P-element induced Wimpy testis (PIWI)-interacting RNAs (piRNAs) are small non-coding RNAs that interact with PIWI proteins and guide them to silence transposable elements. They are abundantly expressed in germline cells and play key roles in spermatogenesis. There is mounting evidence that piRNAs are also present in somatic cells, where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta cell activities...
July 16, 2017: Diabetologia
https://www.readbyqxmd.com/read/28711285/anti-il-21-monoclonal-antibody-combined-with-liraglutide-effectively-reverses-established-hyperglycemia-in-mouse-models-of-type-1-diabetes
#16
Anna K Rydén, Nikole R Perdue, Philippe P Pagni, Claire B Gibson, Sowbarnika S Ratliff, Rikke K Kirk, Travis J Friesen, Claus Haase, Ken Coppieters, Matthias G von Herrath, Tamar E Boursalian
Immunotherapy for type 1 diabetes (T1D) has previously focused on suppressing the autoimmune response against pancreatic beta cells to preserve endogenous insulin production and regulate glucose levels. With increased attention toward combination therapy strategies, studies indicate the multifunctional cytokine interleukin-21 (IL-21) may be a suitable target as an immuno-modulatory arm, while glucagon-like peptide-1 receptor (GLP-1R) agonists may be appropriate as a beta cell protective arm in combination therapy for T1D...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28710530/proteomic-characterisation-reveals-active-wnt-signalling-by-human-multipotent-stromal-cells-as-a-key-regulator-of-beta-cell-survival-and-proliferation
#17
Miljan Kuljanin, Gillian I Bell, Stephen E Sherman, Gilles A Lajoie, David A Hess
AIMS/HYPOTHESIS: Novel strategies to stimulate the expansion of beta cell mass in situ are warranted for diabetes therapy. The aim of this study was to elucidate the secretome of human bone marrow (BM)-derived multipotent stromal cells (MSCs) with documented islet regenerative paracrine function. We hypothesised that regenerative MSCs will secrete a unique combination of protein factors that augment islet regeneration. METHODS: Human BM-derived MSCs were examined for glucose-lowering capacity after transplantation into streptozotocin-treated NOD/severe combined immunodeficiency (SCID) mice and segregated into samples with regenerative (MSC(R)) vs nonregenerative (MSC(NR)) capacity...
July 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28706401/influence-of-west-african-ethnicity-and-gender-on-beta-cell-function-and-insulin-sensitivity-in-essential-hypertensives-treated-with-hydrochlorothiazide-and-hydrochlorothiazide-lisinopril-combination
#18
Micheal Olamoyegun, Babatope Kolawole, Adesuyi A L Ajayi
OBJECTIVE: To assess the effects of hydrochlorothiazide (HCT) given alone and in combination with an angiotensin-converting enzyme inhibitor (ACEI) on beta-cell function in a negroid population to further explore possible ethnic differences in the effect of antihypertensive drugs on homeostasis model assessment - insulin resistance (HOMA-IR). MATERIALS AND METHODS: A total of 80 newly diagnosed Nigerian essential hypertensive patients were assigned to receive either HCT 25 mg daily or both HCT and lisinopril (Lis; 25/10 mg daily) in an open-label study for 12 weeks...
April 2017: Journal of Pharmacology & Pharmacotherapeutics
https://www.readbyqxmd.com/read/28706084/rationale-and-protocol-for-the-after-diabetes-diagnosis-research-support-system-address-an-incident-and-high-risk-type-1-diabetes-uk-cohort-study
#19
Helen C Walkey, Akaal Kaur, Vassiliki Bravis, Ian F Godsland, Shivani Misra, Alistair J K Williams, Polly J Bingley, David B Dunger, Nick Oliver, Desmond G Johnston
INTRODUCTION: Type 1 diabetes is heterogeneous in its presentation and progression. Variations in clinical presentation between children and adults, and with ethnic group warrant further study in the UK to improve understanding of this heterogeneity. Early interventions to limit beta cell damage in type 1 diabetes are undergoing evaluation, but recruitment is challenging. The protocol presented describes recruitment of people with clinician-assigned, new-onset type 1 diabetes to understand the variation in their manner of clinical presentation, to facilitate recruitment into intervention studies and to create an open-access resource of data and biological samples for future type 1 diabetes research...
July 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/28702205/association-of-arsenobetaine-with-beta-cell-function-assessed-by-homeostasis-model-assessment-homa-in-nondiabetic-koreans-data-from-the-fourth-korea-national-health-and-nutrition-examination-survey-knhanes-2008-2009
#20
Kiook Baek, Namhoon Lee, Insung Chung
BACKGROUND: Arsenic is known as an endocrine disruptor that people are exposed to through various sources such as drinking water and indigestion of marine products. Although some epidemiological and animal studies have reported a correlation between arsenic exposure and diabetes development, there are limited studies regarding the toxic effects of organic arsenic including arsenobetaine on the human body. Here, we analyzed the association between urine arsenobetaine and the homeostasis model assessment of β-cell function (HOMA-β), which is an index for predicting diabetes development and reflecting the function of pancreatic β-cells...
2017: Annals of Occupational and Environmental Medicine
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