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https://www.readbyqxmd.com/read/28223801/phytobioactive-compound-based-nanodelivery-systems-for-the-treatment-of-type-2-diabetes-mellitus-current-status
#1
REVIEW
Palanivel Ganesan, Palanisamy Arulselvan, Dong-Kug Choi
Type 2 diabetes mellitus (T2DM) is a major chronic disease that is prevalent worldwide, and it is characterized by an increase in blood glucose, disturbances in the metabolism, and alteration in insulin secretion. Nowadays, food-based therapy has become an important treatment mode for type 2 diabetes, and phytobioactive compounds have gained an increasing amount of attention to this end because they have an effect on multiple biological functions, including the sustained secretion of insulin and regeneration of pancreatic islets cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28223284/mafa-enables-pdx1-to-effectively-convert-pancreatic-islet-progenitors-and-committed-islet-%C3%AE-cells-into-%C3%AE-cells-in-vivo
#2
Taka-Aki Matsuoka, Satoshi Kawashima, Takeshi Miyatsuka, Shugo Sasaki, Naoki Shimo, Naoto Katakami, Dan Kawamori, Satomi Takebe, Pedro L Herrera, Hideaki Kaneto, Roland Stein, Iichiro Shimomura
Among the therapeutic avenues being explored for replacement of the functional islet β-cell mass lost in Type 1 diabetes (T1D), reprogramming of adult cell types into new β-cells has been actively pursued. Notably, mouse islet α-cells will transdifferentiate into β-cells under conditions of near β-cell loss, a condition similar to T1D. Moreover, human islet α-cells also appear to poised for reprogramming into insulin(+) cells. Here we have generated transgenic mice conditionally expressing the islet β-cell-enriched Mafa and/or Pdx1 transcription factors to examine their potential to transdifferentiate embryonic pan-islet cell Ngn3(+) progenitors and the later glucagon(+) α-cell population into β-cells...
February 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28222394/pancreatoprotective-effects-of-geniotrigona-thoracica-stingless-bee-honey-in-streptozotocin-nicotinamide-induced-male-diabetic-rats
#3
Muhammad Shakir Abdul Aziz, Nelli Giribabu, Pasupuleti Visweswara Rao, Naguib Salleh
: Stingless bee honey (SLBH) has been claimed to possess multiple health benefits. Its anti-diabetic properties are however unknown. In this study, ability of SLBH from Geniotrigona thoracica stingless bee species in ameliorating pancreatic damage and in maintaining metabolic profiles were investigated in diabetic condition. METHODS: SLBH at 1 and 2g/kg/b.w. was given orally to streptozotocin (STZ)-nicotinamide-induced male diabetic rats for 28days. Metabolic parameters (fasting blood glucose-FBG and lipid profiles-LP and serum insulin) were measured by biochemical assays...
February 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28220294/chromogranin-a-regulates-vesicle-storage-and-mitochondrial-dynamics-to-influence-insulin-secretion
#4
Joshua Wollam, Sumana Mahata, Matthew Riopel, Angelina Hernandez-Carretero, Angshuman Biswas, Gautam K Bandyopadhyay, Nai-Wen Chi, Lee E Eiden, Nitish R Mahapatra, Angelo Corti, Nicholas J G Webster, Sushil K Mahata
Chromogranin A (CgA) is a prohormone and a granulogenic factor that regulates secretory pathways in neuroendocrine tissues. In β-cells of the endocrine pancreas, CgA is a major cargo in insulin secretory vesicles. The impact of CgA deficiency on the formation and exocytosis of insulin vesicles is yet to be investigated. In addition, no literature exists on the impact of CgA on mitochondrial function in β-cells. Using three different antibodies, we demonstrate that CgA is processed to vasostatin- and catestatin-containing fragments in pancreatic islet cells...
February 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28220272/exposure-to-chronic-hyperglycemic-conditions-results-in-ras-related-c3-botulinum-toxin-substrate-1-rac1-mediated-activation-of-p53-and-atm-kinase-in-pancreatic-%C3%AE-cells
#5
Vaibhav Sidarala, Anjaneyulu Kowluru
Chronic hyperglycemia (HG) promotes pancreatic islet dysfunction which leads to the onset of T2DM. This study is aimed at defining regulatory roles of Rac1, a small G-protein, in the activation of p53 and ATM kinase in pancreatic β-cells, under the duress of HG conditions. We report significant stimulatory effects of HG (20 mM; 24 h) on p53 activation in INS-1 832/13 cells, normal rodent and human islets. Pharmacological inhibition of Rac1 (EHT1864 or NSC23766) significantly suppressed HG-induced p53 activation in INS-1 832/13 cells and rat islets, suggesting novel roles for this small G-protein in the activation of p53...
February 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28218988/toxicological-effects-during-and-following-persistent-insulin-induced-hypoglycaemia-in-healthy-euglycaemic-rats
#6
Vivi F H Jensen, Anne-Marie Mølck, Line O Berthelsen, Lene Alifrangis, Lene Andersen, Melissa Chapman, Jens Lykkesfeldt, Ingrid B Bøgh
New insulin analogues with a longer duration of action and a "peakless" pharmacokinetic profile have been developed to improve efficacy, safety and convenience for diabetic patients. During non-clinical development, according to regulatory guidelines, these analogues are tested in healthy euglycaemic rats rendering them persistently hypoglycaemic. Little is known about the effect of persistent (24 hr/day) insulin-induced hypoglycaemia (IIH) in rats, complicating interpretation of results in pre-clinical studies with new longer-acting insulin analogues...
February 20, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28215845/converting-adult-pancreatic-islet-%C3%AE-cells-into-%C3%AE-cells-by-targeting-both-dnmt1-and-arx
#7
Harini Chakravarthy, Xueying Gu, Martin Enge, Xiaoqing Dai, Yong Wang, Nicolas Damond, Carolina Downie, Kathy Liu, Jing Wang, Yuan Xing, Simona Chera, Fabrizio Thorel, Stephen Quake, Jose Oberholzer, Patrick E MacDonald, Pedro L Herrera, Seung K Kim
Insulin-producing pancreatic β cells in mice can slowly regenerate from glucagon-producing α cells in settings like β cell loss, but the basis of this conversion is unknown. Moreover, it remains unclear if this intra-islet cell conversion is relevant to diseases like type 1 diabetes (T1D). We show that the α cell regulators Aristaless-related homeobox (Arx) and DNA methyltransferase 1 (Dnmt1) maintain α cell identity in mice. Within 3 months of Dnmt1 and Arx loss, lineage tracing and single-cell RNA sequencing revealed extensive α cell conversion into progeny resembling native β cells...
February 12, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28213757/germinal-centre-frequency-is-decreased-in-pancreatic-lymph-nodes-from-individuals-with-recent-onset-type-1-diabetes
#8
Abby Willcox, Sarah J Richardson, Lucy S K Walker, Sally C Kent, Noel G Morgan, Kathleen M Gillespie
AIMS/HYPOTHESIS: Pancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes. METHODS: Immunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1...
February 17, 2017: Diabetologia
https://www.readbyqxmd.com/read/28213664/type-2-diabetes-remission-after-roux-en-y-gastric-bypass-evidence-for-increased-expression-of-jejunal-genes-encoding-regenerating-pancreatic-islet-derived-proteins-as-a-potential-mechanism
#9
Priscila Sala, Raquel Susana Torrinhas, Danielle Cristina Fonseca, Steven Heymsfield, Daniel Giannella-Neto, Dan Linetzky Waitzberg
BACKGROUND: Intestinal expression of regenerating pancreatic islet-derived protein-encoding genes (REG) would be enhanced after Roux-en-Y gastric bypass (RYGB) and would affect postoperative type 2 diabetes remission (T2Dr). METHODS: Intestinal biopsy samples were collected from 20 adult obese women with T2D before and 3 months after RYGB. Levels of REG expression and the gene encoding its putative receptor (EXTL3) were assessed by microarray and validated by quantitative RT-PCR...
February 17, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28212332/type-1-diabetes-candidate-genes-linked-to-pancreatic-islet-cell-inflammation-and-beta-cell-apoptosis
#10
REVIEW
Joachim Størling, Flemming Pociot
Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28211608/preclinical-characterisation-of-55p0251-a-novel-compound-that-amplifies-glucose-stimulated-insulin-secretion-and-counteracts-hyperglycaemia-in-rodents
#11
Karin Stadlbauer, Barbara Brunmair, Zsuzsanna Lehner, Immanuel Adorjan, Thomas Scherer, Anton Luger, Leonhardt Bauer, Clemens Fürnsinn
AIMS: 55P0251 is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action. MATERIALS AND METHODS: Pharmacokinetic properties of 55P0251 were portrayed in several species. First efforts to elucidate the glucose lowering mechanism in rodents included numerous experimental protocols dealing with glucose tolerance, insulin secretion from isolated pancreatic islets, and comparison to established drugs...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28208792/an%C3%A2-exercise-only%C3%A2-intervention%C3%A2-in%C3%A2-obese%C3%A2-fathers%C3%A2-restores%C3%A2-glucose%C3%A2-and%C3%A2-insulin%C3%A2-regulation%C3%A2-in%C3%A2-conjunction%C3%A2-with%C3%A2-the%C3%A2-rescue%C3%A2-of%C3%A2-pancreatic%C3%A2-islet%C3%A2-cell%C3%A2-morphology%C3%A2-and%C3%A2-microrna%C3%A2-expression%C3%A2-in%C3%A2-male%C3%A2-offspring
#12
Nicole O McPherson, Michelle Lane, Lauren Sandeman, Julie A Owens, Tod Fullston
Paternal obesity programs metabolic syndrome in offspring. Low-impact exercise in obese  males improves the metabolic health of female offspring, however whether this occurred in male  offspring remained unknown. C57BL/6NHsd (Harlan) mice were fed a control diet (CD; 6% fat, n =  7) or a high-fat diet (HFD; 21% fat, n = 16) for 18 weeks. After 9 weeks, HFD-fed mice either remained  sedentary (HH, n = 8) or undertook low-moderate exercise (HE, n = 8) for another 9 weeks...
February 9, 2017: Nutrients
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#13
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) (PDLLCL) scaffold...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28202581/identification-and-functional-implications-of-sodium-myo-inositol-cotransporter-1-in-pancreatic-beta-cells-and-type-2-diabetes-mellitus
#14
Stephen Yu Ting Li, Sam Tsz Wai Cheng, Dan Zhang, Po Sing Leung
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28202288/tiam1-vav2-rac1-axis-a-tug-of-war-between-islet-function-and-dysfunction
#15
REVIEW
Anjaneyulu Kowluru
Glucose-stimulated insulin secretion [GSIS] from the islet β-cell involves a well-orchestrated interplay between metabolic and cationic events. It is well established that intracellular generation of adenine and guanine nucleotide triphosphates [e.g., ATP and GTP] represents one of the requisite signaling steps in GSIS. The small molecular mass GTP-binding proteins [G-proteins; e.g., Rac1 and Cdc42] have been shown to regulate islet β-cell function including actin cytoskeletal remodeling and fusion of insulin granules with the plasma membrane for GSIS to occur...
February 12, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28198575/tat-biliverdin-reductase-a-protects-ins-1-cells-from-human-islet-amyloid-polypeptide-induced-cytotoxicity-by-alleviating-oxidative-stress-and-er-stress
#16
Su Jin Lee, Hyung Kyung Kang, Won Sik Eum, Jinseu Park, Soo Young Choi, Hyeok Yil Kwon
Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β-cell apoptosis and eventually contributes to β-cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat-mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS-1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP-induced apoptosis and dysfunction in insulin secretion in β-cells. Tat-BLVRA fusion protein was efficiently delivered into INS-1 cells in a time- and dose-dependent manner...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28197316/design-and-synthesis-of-novel-selective-gpr40-agopams
#17
Christopher W Plummer, Matthew J Clements, Helen Chen, Murali Rajagopalan, Hubert Josien, William K Hagmann, Michael Miller, Maria E Trujillo, Melissa Kirkland, Daniel Kosinski, Joel Mane, Michele Pachanski, Boonlert Cheewatrakoolpong, Andrew F Nolting, Robert Orr, Melodie Christensen, Louis-Charles Campeau, Michael J Wright, Randal Bugianesi, Sarah Souza, Xiaoping Zhang, Jerry Di Salvo, Adam B Weinglass, Richard Tschirret-Guth, Ravi Nargund, Andrew D Howard, Steven L Colletti
GPR40 is a G-protein-coupled receptor expressed primarily in pancreatic islets and intestinal L-cells that has been a target of significant recent therapeutic interest for type II diabetes. Activation of GPR40 by partial agonists elicits insulin secretion only in the presence of elevated blood glucose levels, minimizing the risk of hypoglycemia. GPR40 agoPAMs have shown superior efficacy to partial agonists as assessed in a glucose tolerability test (GTT). Herein, we report the discovery and optimization of a series of potent, selective GPR40 agoPAMs...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28193859/genetic-regulatory-signatures-underlying-islet-gene-expression-and-type-2-diabetes
#18
Arushi Varshney, Laura J Scott, Ryan P Welch, Michael R Erdos, Peter S Chines, Narisu Narisu, Ricardo D'O Albanus, Peter Orchard, Brooke N Wolford, Romy Kursawe, Swarooparani Vadlamudi, Maren E Cannon, John P Didion, John Hensley, Anthony Kirilusha, Lori L Bonnycastle, D Leland Taylor, Richard Watanabe, Karen L Mohlke, Michael Boehnke, Francis S Collins, Stephen C J Parker, Michael L Stitzel
Genome-wide association studies (GWAS) have identified >100 independent SNPs that modulate the risk of type 2 diabetes (T2D) and related traits. However, the pathogenic mechanisms of most of these SNPs remain elusive. Here, we examined genomic, epigenomic, and transcriptomic profiles in human pancreatic islets to understand the links between genetic variation, chromatin landscape, and gene expression in the context of T2D. We first integrated genome and transcriptome variation across 112 islet samples to produce dense cis-expression quantitative trait loci (cis-eQTL) maps...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#19
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28193492/characterization-of-acyl-coa-synthetase-isoforms-in-pancreatic-beta-cells-gene-silencing-shows-participation-of-acsl3-and-acsl4-in-insulin-secretion
#20
Israr-Ul H Ansari, Melissa J Longacre, Scott W Stoker, Mindy A Kendrick, Lucas M O'Neill, Laura J Zitur, Luis A Fernandez, James M Ntambi, Michael J MacDonald
Long-chain acyl-CoA synthetases (ACSLs) convert fatty acids to fatty acyl-CoAs to regulate various physiologic processes. We characterized the ACSL isoforms in a cell line of homogeneous rat beta cells (INS-1 832/13 cells) and human pancreatic islets. ACSL4 and ACSL3 proteins were present in the beta cells and human and rat pancreatic islets and concentrated in insulin secretory granules and less in mitochondria and negligible in other intracellular organelles. ACSL1 and ACSL6 proteins were not seen in INS-1 832/13 cells or pancreatic islets...
February 11, 2017: Archives of Biochemistry and Biophysics
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