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https://www.readbyqxmd.com/read/29346712/synergetic-effects-of-prenatal-and-postnatal-high-sucrose-intake-on-glucose-tolerance-and-hepatic-insulin-resistance-in-rat-offspring
#1
Pengjie Zhang, Di Zhu, Yueming Zhang, Lingjun Li, Xionghui Chen, Wenna Zhang, Ruixiu Shi, Jianying Tao, Bing Han, Zhice Xu
SCOPE: High sucrose intake during pregnancy is linked to type 2 diabetes mellitus and altered insulin resistance. METHODS AND RESULTS: This study attempted to ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the detrimental effects of high postnatal sugar consumption in the offspring, and the molecular mechanisms were investigated using a rat model. High prenatal sucrose exposure increased the body weight of the offspring at 1 to 3 weeks of age...
January 18, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29346396/serum-mirna-levels-are-related-to-glucose-homeostasis-and-islet-autoantibodies-in-children-with-high-risk-for-type-1-diabetes
#2
Linda Åkerman, Rosaura Casas, Johnny Ludvigsson, Beatriz Tavira, Camilla Skoglund
Micro RNAs (miRNAs) are promising disease biomarkers due to their high stability. Their expression in serum is altered in type 1 diabetes, but whether deviations exist in individuals with high risk for type 1 diabetes remains unexplored. We therefore assessed serum miRNAs in high-risk individuals (n = 21) positive for multiple islet autoantibodies, age-matched healthy children (n = 17) and recent-onset type 1 diabetes patients (n = 8), using Serum/Plasma Focus microRNA PCR Panels from Exiqon. The miRNA levels in the high-risk group were similar to healthy controls, and no specific miRNA profile was identified for the high-risk group...
2018: PloS One
https://www.readbyqxmd.com/read/29345360/mtor-a-double-edged-sword-for-diabetes
#3
REVIEW
Yali Tuo, Ming Xiang
Diabetes is both a metabolic and an immune disorder. One intriguing link between the two is the serine-threonine protein kinase mammalian target of rapamycin (mTOR). As a component of the PI3K/Akt pathway and other cellular signals, mTOR is a key regulator of fuel metabolism and function of both pancreatic islet β cells and immune cells. Consequently, it seems that mTOR has both anti- and prodiabetic effects. On the one hand, activation of mTOR in β cells can increase their growth and proliferation, opposing impairments of insulin secretion in diabetes...
January 9, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29343652/painless-thyroiditis-and-fulminant-type-1-diabetes-mellitus-in-a-patient-treated-with-an-immune-checkpoint-inhibitor-nivolumab
#4
Kanako Sakurai, Satsuki Niitsuma, Ryota Sato, Kazuhiro Takahashi, Zenei Arihara
The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. Nivolumab, an anti-PD-1 monoclonal antibody, blocks PD-1 and can restore anti-cancer immune responses by disrupting the signal that inhibits T-cell activation. Nivolumab may induce endocrine-related adverse events, including hypophysitis, autoimmune thyroiditis, and type 1 diabetes mellitus. Here we report a 68-year-old female patient with advanced renal cell carcinoma who was treated with nivolumab...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29343548/loss-of-b-cell-anergy-in-type-1-diabetes-is-associated-with-high-risk-hla-and-non-hla-disease-susceptibility-alleles
#5
Mia J Smith, Marynette Rihanek, Clive Wasserfall, Clayton E Mathews, Mark A Atkinson, Peter A Gottlieb, John C Cambier
Although B cells reactive with islet autoantigens are silenced by tolerance mechanisms in healthy individuals, they can become activated and contribute to development of type 1 diabetes. We previously demonstrated that high-affinity insulin-binding B cells (IBCs) occur exclusively in the anergic (BND) compartment in peripheral blood of healthy subjects. Consistent with their activation early in disease development, high-affinity IBCs are absent from the BND compartment of some first-degree relatives (FDRs) as well as all autoantibody positive pre-diabetic and new-onset type 1 diabetes patients, a time when they are found in pancreatic islets...
January 17, 2018: Diabetes
https://www.readbyqxmd.com/read/29343547/molecular-pathways-for-immune-recognition-of-preproinsulin-signal-peptide-in-type-1-diabetes
#6
Deborah Kronenberg-Versteeg, Martin Eichmann, Mark A Russell, Arnoud de Ru, Beate Hehn, Norkhairin Yusuf, Peter A van Veelen, Sarah J Richardson, Noel G Morgan, Marius K Lemberg, Mark Peakman
The signal peptide region of preproinsulin (PPI) contains epitopes targeted by human leucocyte antigen-A (HLA-A)-restricted (HLA-A0201, A2402) cytotoxic T-cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended PPI epitope discovery to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles revealing that 4/6 alleles present epitopes derived from the signal peptide region. During co-translational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical, proteasome-directed pathway...
January 17, 2018: Diabetes
https://www.readbyqxmd.com/read/29343517/early-infant-diet-and-islet-autoimmunity-in-the-teddy-study
#7
Ulla Uusitalo, Hye-Seung Lee, Carin Andrén Aronsson, Kendra Vehik, Jimin Yang, Sandra Hummel, Katherine Silvis, Åke Lernmark, Marian Rewers, William Hagopian, Jin-Xiong She, Olli Simell, Jorma Toppari, Anette-G Ziegler, Beena Akolkar, Jeffrey Krischer, Suvi M Virtanen, Jill M Norris
OBJECTIVE: To examine duration of breastfeeding and timing of complementary foods and risk of islet autoimmunity (IA). RESEARCH DESIGN AND METHODS: The TEDDY study prospectively follows 8,676 children with increased genetic risk of type 1 diabetes (T1D) in the U.S., Finland, Germany, and Sweden. This study included 7,563 children with at least 9 months of follow-up. Blood samples were collected every 3 months from birth to evaluate IA, defined as persistent, confirmed positive insulin autoantibodies (IAAs), glutamic acid decarboxylase, or insulinoma antigen-2...
January 17, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29342984/amaranthus-caudatus-stimulates-insulin-secretion-in-goto-kakizaki-rats-a-model-of-diabetes-mellitus-type-2
#8
Silvia Zambrana, Lena C E Lundqvist, Virginia Veliz, Sergiu-Bogdan Catrina, Eduardo Gonzales, Claes-Göran Östenson
Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a pseudo-cereal with reported anti-diabetic effects that is usually consumed in food preparations in Bolivia. This study evaluated the anti-diabetic nutraceutical property of an AC hydroethanolic extract that contains mainly sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)), in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats...
January 15, 2018: Nutrients
https://www.readbyqxmd.com/read/29341416/resveratrol-influences-pancreatic-islets-by-opposing-effects-on-electrical-activity-and-insulin-release
#9
Simone Brouwer, Theresa Hoffmeister, Anne Gresch, Lisa Schönhoff, Martina Düfer
SCOPE: Resveratrol is suggested to improve glycemic control by activation of sirtuin 1 (SIRT1) and has already been tested clinically. Our investigation characterizes the targets of resveratrol in pancreatic beta cells and their contribution to short- and long-term effects on insulin secretion. METHODS AND RESULTS: Islets or beta cells were isolated from C57Bl/6N mice. Electrophysiology was performed with microelectrode arrays and patch-clamp technique, insulin secretion and content were determined by radioimmunoassay, cAMP was measured by enzyme-linked immunosorbent assay and cytosolic Ca2+ concentration by fluorescence methods...
January 17, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29339498/mafa-missense-mutation-causes-familial-insulinomatosis-and-diabetes-mellitus
#10
Donato Iacovazzo, Sarah E Flanagan, Emily Walker, Rosana Quezado, Fernando Antonio de Sousa Barros, Richard Caswell, Matthew B Johnson, Matthew Wakeling, Michael Brändle, Min Guo, Mary N Dang, Plamena Gabrovska, Bruno Niederle, Emanuel Christ, Stefan Jenni, Bence Sipos, Maike Nieser, Andrea Frilling, Ketan Dhatariya, Philippe Chanson, Wouter W de Herder, Björn Konukiewitz, Günter Klöppel, Roland Stein, Márta Korbonits, Sian Ellard
The β-cell-enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing MAFA variants have been previously described. We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we identified a missense MAFA mutation (p...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338697/additional-dexamethasone-in-chemotherapies-with-carboplatin-and-paclitaxel-could-reduce-the-impaired-glycometabolism-in-rat-models
#11
Yanxiu Guo, Haoxia Zeng, Xiaohong Chang, Chaohua Wang, Heng Cui
BACKGROUND: Side-effects have been considered as the limitation of the chemotherapy agents' administration and life quality in patients with ovarian cancers. In order to explore the influence of the chemotherapy agents commonly used in ovarian cancer patients on the blood glucose metabolism in rat models, we conducted this study which simulated the conditions of clinical protocols. METHODS: Eighty clean-grade female Wistar rats were randomized into 8 groups: Group 1 (Negative control), Group 1' (Dexamethasone), Group 2 (Carboplatin), Group 2' (Carboplatin-plus-dexamethasone), Group 3 (Paclitaxel), Group 3' (Paclitaxel-plus-dexamethasone), Group 4 (Combined therapy), Group 4' (Combined-therapy-plus-dexamethasone)...
January 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29338388/novel-fusion-protein-targeting-mitochondrial-dna-improves-pancreatic-islet-functional-potency-and-islet-transplantation-outcomes
#12
Juan S Danobeitia, Peter J Chlebeck, Inna Shokolenko, Xiaobo Ma, Glenn Wilson, Luis A Fernandez
Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29338387/quantifying-the-effects-of-different-neutral-proteases-on-human-islet-integrity
#13
Heide Brandhorst, Paul R V Johnson, Olle Korsgren, Daniel Brandhorst
Efficient islet release from the pancreas requires the combination of collagenase, neutral protease (cNP), or thermolysin (TL). Recently, it has been shown that clostripain (CP) may also contribute to efficient islet release from the human pancreas. The aim of this study was to evaluate the impact of these proteases on human islet integrity in a prospective approach. Islets were isolated from the pancreas of 10 brain-dead human organ donors. Purified islets were precultured for 3 to 4 d at 37 °C to ensure that preparations were cleared of predamaged islets, and only integral islets were subjected to 90 min of incubation at 37 °C in Hank's balanced salt solution supplemented with cNP, TL, or CP...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29338381/effect-of-the-diabetic-state-on-islet-engraftment-and-function-in-a-large-animal-model-of-islet-kidney-transplantation
#14
Prashanth Vallabhajosyula, Atsushi Hirakata, Matthew Weiss, Adam Griesemer, Akira Shimizu, Hanzhou Hong, Andreas Habertheuer, Vaja Tchipashvili, Kazuhiko Yamada, David H Sachs
In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29337308/rage-binds-preamyloid-iapp-intermediates-and-mediates-pancreatic-%C3%AE-cell-proteotoxicity
#15
Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P Raleigh, Ann Marie Schmidt
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337137/basal-mitophagy-occurs-independently-of-pink1-in-mouse-tissues-of-high-metabolic-demand
#16
Thomas G McWilliams, Alan R Prescott, Lambert Montava-Garriga, Graeme Ball, François Singh, Erica Barini, Miratul M K Muqit, Simon P Brooks, Ian G Ganley
Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Using mito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues. We observed a high degree of mitophagy in neural cells, including PD-relevant mesencephalic dopaminergic neurons and microglia...
January 10, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29337057/heterogeneity-of-autophagic-status-in-pancreatic-%C3%AE-cells-under-metabolic-stress
#17
Mai Kamitani, Takeshi Miyatsuka, Masaki Miura, Kosuke Azuma, Luka Suzuki, Miwa Himuro, Takehiro Katahira, Yuya Nishida, Yoshio Fujitani, Hirotaka Watada
Autophagy in β cells has been demonstrated to play a pivotal role in cellular homeostasis and the progression of glucose intolerance. Although autophagic activity is affected by metabolic stress both in vivo and in vitro, it remains unclear as to what extent the autophagic status in each β cell is different from its neighboring cells. To address this question, GFP-LC3 reporter mice, which can visualize the autophagic status of each β cell as green-fluorescent puncta, were crossed with obese diabetic db/db mice...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29335884/effects-of-moderate-exercise-on-biochemical-morphological-and-physiological-parameters-of-the-pancreas-of-female-mice-with-estrogen-deprivation-and-dyslipidemia
#18
Aparecida Gabriela Bexiga Veloso, Nathalia Edviges Alves Lima, Elisabete de Marco Ornelas, Clever Gomes Cardoso, Mara Rubia Marques, Beatriz da Costa Aguiar Alves Reis, Fernando Luiz Affonso Fonseca, Laura Beatriz Mesiano Maifrino
Menopausal women are at high risk of developing heart disease. However, physical exercise practice can reverse this scenario. We evaluated the biochemical, morphological, and physiological effects of moderate aerobic physical exercise on the pancreas of knockout mice for LDL receptor with estrogen deprivation by ovariectomy. Animals were divided into six groups (n = 5): sedentary non-ovariectomized control; sedentary ovariectomized control; trained ovariectomized control; sedentary non-ovariectomized LDL-R knockout; sedentary ovariectomized LDL-R knockout; and trained ovariectomized LDL-R knockout...
January 15, 2018: Medical Molecular Morphology
https://www.readbyqxmd.com/read/29335487/increased-expression-of-glp-1r-in-proliferating-islets-of-men1-mice-is-detectable-by-68ga-ga-do3a-vs-cys40-exendin-4-pet
#19
Azita Monazzam, Joey Lau, Irina Velikyan, Su-Chen Li, Masoud Razmara, Ulrika Rosenström, Olof Eriksson, Britt Skogseid
Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29333922/effect-of-resveratrol-treatment-on-graft-revascularization-after-islet-transplantation-in-streptozotocin-induced-diabetic-mice
#20
Eun-Mi Lee, Inwon Park, Ye-Jee Lee, Young-Hye You, Ji-Won Kim, Myung-Jun Kim, Yu-Bae Ahn, Pilhan Kim, Seung-Hyun Ko
We evaluated the effect of resveratrol (RSV) on graft survival after islet transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200 IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 μM) were incubated in a hypoxic chamber (O2 1%, 1hr)...
January 15, 2018: Islets
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