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https://www.readbyqxmd.com/read/29033899/environmental-factors-contribute-to-%C3%AE-cell-endoplasmic-reticulum-stress-and-neo-antigen-formation-in-type-1-diabetes
#1
Meghan L Marré, Jon D Piganelli
Type 1 diabetes (T1D) is an autoimmune disease in which immune-mediated targeting and destruction of insulin-producing pancreatic islet β cells leads to chronic hyperglycemia. There are many β cell proteins that are targeted by autoreactive T cells in their native state. However, recent studies have demonstrated that many β cell proteins are recognized as neo-antigens following posttranslational modification (PTM). Although modified neo-antigens are well-established targets of pathology in other autoimmune diseases, the effects of neo-antigens in T1D progression and the mechanisms by which they are generated are not well understood...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29031732/neonatal-pancreatic-pericytes-support-%C3%AE-cell-proliferation
#2
Alona Epshtein, Eleonor Rachi, Lina Sakhneny, Shani Mizrachi, Daria Baer, Limor Landsman
OBJECTIVE: The maintenance and expansion of β-cell mass rely on their proliferation, which reaches its peak in the neonatal stage. β-cell proliferation was found to rely on cells of the islet microenvironment. We hypothesized that pericytes, which are components of the islet vasculature, support neonatal β-cell proliferation. METHODS: To test our hypothesis, we combined in vivo and in vitro approaches. Briefly, we used a Diphtheria toxin-based transgenic mouse system to specifically deplete neonatal pancreatic pericytes in vivo...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031729/point-mutation-of-ffar1-abrogates-fatty-acid-dependent-insulin-secretion-but-protects-against-hfd-induced-glucose-intolerance
#3
Sibylle Sabrautzki, Gabriele Kaiser, Gerhard K H Przemeck, Felicia Gerst, Estela Lorza-Gil, Madhura Panse, Tina Sartorius, Miriam Hoene, Susan Marschall, Hans-Ulrich Häring, Martin Hrabě de Angelis, Susanne Ullrich
OBJECTIVE: The fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-dependent augmentation of glucose-induced insulin secretion (GIIS) in pancreatic β-cells. Genetically engineered Ffar1-knockout/congenic mice univocally displayed impaired fatty acid-mediated insulin secretion, but in vivo experiments delivered controversial results regarding the function of FFAR1 in glucose homeostasis and liver steatosis. This study presents a new coisogenic mouse model carrying a point mutation in Ffar1 with functional consequence...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031723/inhibition-of-cholinergic-potentiation-of-insulin-secretion-from-pancreatic-islets-by-chronic-elevation-of-glucose-and-fatty-acids-protection-by-casein-kinase-2-inhibitor
#4
Nicolai M Doliba, Qin Liu, Changhong Li, Pan Chen, Chengyang Liu, Ali Naji, Franz M Matschinsky
OBJECTIVES: Chronic hyperlipidemia and hyperglycemia are characteristic features of type 2 diabetes (T2DM) that are thought to cause or contribute to β-cell dysfunction by "glucolipotoxicity." Previously we have shown that acute treatment of pancreatic islets with fatty acids (FA) decreases acetylcholine-potentiated insulin secretion. This acetylcholine response is mediated by M3 muscarinic receptors, which play a key role in regulating β-cell function. Here we examine whether chronic FA exposure also inhibits acetylcholine-potentiated insulin secretion using mouse and human islets...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031208/phytoecdysteroids-from-ajuga-iva-act-as-potential-antidiabetic-agent-against-alloxan-induced-diabetic-male-albino-rats
#5
Jin-Jun Wang, Hao Jin, Shao-Ling Zheng, Peng Xia, Yong Cai, Xiao-Jie Ni
The present study investigated the protective effect of phytoecdysteroids extracted from the Ajuga iva plant on body weight changes, blood glucose, insulin total protein, blood urea nitrogen (BUN), creatinine, triglycerides (TG), cholesterol, lipid peroxidation, antioxidant enzymes, pancreatic histopathology and hexokinase-I expression in the alloxan-induced diabetic rats. Experimental diabetes was induced following 15day intraperitoneal administration of alloxan. The rats were divided into four groups. Group I served as a sham group, and group II served as the diabetic control...
October 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29029025/insulin-deficient-mouse-%C3%AE-cells-do-not-fully-mature-but-can-be-remedied-through-insulin-replacement-by-islet-transplantation
#6
Adam Ramzy, Majid Mojibian, Timothy J Kieffer
Insulin receptor insufficiency in β-cells leads to impaired insulin secretion and reduced β-cell hyperplasia in response to hyperglycemia. Selective insulin receptor deficiency in β-cells in later embryological development may lead to compensatory β-cell hyperplasia. Though these findings suggest insulin signaling on the β-cell is important for β-cell function, they are confounded by loss of signaling by the IGFs through the insulin receptor. To determine if insulin itself is necessary for β-cell development and maturation, we performed a characterization of pancreatic islets in mice with deletions of both non-allelic insulin genes (Ins1-/-Ins2-/-)...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/29026155/trk-fused-gene-tfg-regulates-pancreatic-%C3%AE-cell-mass-and-insulin-secretory-activity
#7
Takeshi Yamamotoya, Yusuke Nakatsu, Akifumi Kushiyama, Yasuka Matsunaga, Koji Ueda, Yuki Inoue, Masa-Ki Inoue, Hideyuki Sakoda, Midori Fujishiro, Hiraku Ono, Hiroshi Kiyonari, Hisamitsu Ishihara, Tomoichiro Asano
The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated vesicle transport and missense mutations in TFG cause several neurodegenerative diseases including hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes mellitus suggests TFG to have an important role(s) in glucose homeostasis. To examine this possibility, β-cell specific TFG knockout mice (βTFG KO) were generated. Interestingly, βTFG KO displayed marked glucose intolerance with reduced insulin secretion...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29025046/decreased-insulin-secretion-in-pregnant-rats-fed-a-low-protein-diet
#8
Haijun Gao, Eric Ho, Meena Balakrishnan, Vijay Yechoor, Chandra Yallampalli
Low protein (LP) diet during pregnancy leads to reduced plasma insulin levels in rodents, but the underlying mechanisms remain unclear. Glucose is the primary insulin secretagogue and enhanced glucose stimulated insulin secretion (GSIS) in beta cells contributes to compensation for insulin resistance and maintenance of glucose homeostasis during pregnancy. In this study we hypothesized that plasma insulin levels in pregnant rats fed LP diet is reduced due to disrupted GSIS of pancreatic islets. We first confirmed reduced plasma insulin levels, then investigated in vivo insulin secretion by glucose tolerance test and ex vivo GSIS of pancreatic islets in the presence of glucose at different doses, and KCl, glibenclamide and L-arginine...
August 28, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29024725/glucagon-a-key-factor-in-the-pathophysiology-of-type-2-diabetes
#9
REVIEW
Jean Girard
Excessive circulating glucagon levels have been reported in all forms of diabetes, clinical or experimental. The hyperglucagonemia of diabetes results from an excessive secretion of the hormone secondary from a deficit in insulin secretion and/or a dysfunction of various cells within the islets of Langerhans (somatostatin) leading to the notion of "paracrinopathy". Hyperglucagonemia contributes to the fasting and postprandial hyperglycemia in diabetic patients through an increased hepatic glucose production (mainly gluconeogenesis)...
October 9, 2017: Biochimie
https://www.readbyqxmd.com/read/29022222/t-cell-receptor-profiling-in-type-1-diabetes
#10
REVIEW
Laura M Jacobsen, Amanda Posgai, Howard R Seay, Michael J Haller, Todd M Brusko
PURPOSE OF REVIEW: The genetic susceptibility and dominant protection for type 1 diabetes (T1D) associated with human leukocyte antigen (HLA) haplotypes, along with minor risk variants, have long been thought to shape the T cell receptor (TCR) repertoire and eventual phenotype of autoreactive T cells that mediate β-cell destruction. While autoantibodies provide robust markers of disease progression, early studies tracking autoreactive T cells largely failed to achieve clinical utility...
October 11, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/29021697/chronic-saponin-treatment-attenuates-damage-to-the-pancreas-in-chronic-alcohol-treated-diabetic-rats
#11
Mi Ran Choi, Su Min Kwak, Sol Hee Bang, Jo-Eun Jeong, Dai-Jin Kim
BACKGROUND: Chronic heavy alcohol consumption may raise the risk of developing type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells and reduce lipid parameters. The present study was designed to investigate the effect of saponin on chronic ethanol-treated diabetic rats. METHODS: Long-Evans Tokushima Fatty (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats were pair-fed a Lieber-DeCarli diet with and without 5% ethanol for 12 wks...
October 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/29021486/a-hypoglycemia-inducing-giant-borderline-phyllodes-tumor-secreting-high-molecular-weight-insulin-like-growth-factor-ii-a-case-report-with-immunohistochemistry-and-a-western-blot-analysis
#12
Masahiro Hikichi, Yuka Kiriyama, Takanori Hayashi, Kaori Ushimado, Naomi Kobayashi, Makoto Urano, Makoto Kuroda, Toshiaki Utsumi
A 50-year-old woman with a large right breast mass was emergently hospitalized for generalized weakness and fatigue. A histological examination of tumor biopsy specimens revealed a phyllodes tumor (PT). She suddenly lost consciousness due to severe hypoglycemia. Non-islet cell tumor hypoglycemia (NICTH) due to the PT was suspected. The tumor was emergently resected. A histological examination revealed a borderline PT. The patient recovered from the hypoglycemic episode. High-molecular-weight insulin-like growth factor II was detected in serum that had been collected preoperatively and in the tumor tissue, but not in serum that had been collected postoperatively...
October 11, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29018828/repurposing-lesogaberan-to-promote-human-islet-cell-survival-and-%C3%AE-cell-replication
#13
Jide Tian, Hoa Dang, Angela Hu, Willem Xu, Daniel L Kaufman
The activation of β-cell's A- and B-type gamma-aminobutyric acid receptors (GABAA-Rs and GABAB-Rs) can promote their survival and replication, and the activation of α-cell GABAA-Rs promotes their conversion into β-cells. However, GABA and the most clinically applicable GABA-R ligands may be suboptimal for the long-term treatment of diabetes due to their pharmacological properties or potential side-effects on the central nervous system (CNS). Lesogaberan (AZD3355) is a peripherally restricted high-affinity GABAB-R-specific agonist, originally developed for the treatment of gastroesophageal reflux disease (GERD) that appears to be safe for human use...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29017142/mechanisms-of-antidiabetic-effects-of-flavonoid-rutin
#14
REVIEW
Ahmad Ghorbani
Several lines of evidence suggest that flavonoids that originated from vegetables and medicinal plants have beneficial effects on diabetes by improving glycemic control, lipid profile, and antioxidant status. Rutin is a flavonoid found in many plants and shows a wide range of biological activities including anti-inflammatory, antioxidant, neuroprotective, nephroprotective, and hepatoprotective effects. In this review, the antihyperglycemic property of rutin and its protective effects against the development of diabetic complications are discussed...
October 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28993948/a-model-for-cell-migration-in-non-isotropic-fibrin-networks-with-an-application-to-pancreatic-tumor-islets
#15
Jiao Chen, Daphne Weihs, Fred J Vermolen
Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk...
October 9, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28993759/the-four-way-stop-sign-viruses-12-lipoxygenase-islets-and-natural-killer-cells-in-type-1-diabetes-progression
#16
Michele L Semeraro, Lindsey M Glenn, Margaret A Morris
Natural killer (NK) cells represent an important effector arm against viral infection, and mounting evidence suggests that viral infection plays a role in the development of type 1 diabetes (T1D) in at least a portion of patients. NK cells recognize their target cells through a delicate balance of inhibitory and stimulatory receptors on their surface. If unbalanced, NK cells have great potential to wreak havoc in the pancreas due to the beta cell expression of the as-yet-defined NKp46 ligand through interactions with the activating NKp46 receptor found on the surface of most NK cells...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28993202/temporal-expression-profiling-of-plasma-proteins-reveals-oxidative-stress-in-early-stages-of-type-1-diabetes-progression
#17
Chih-Wei Liu, Lisa Bramer, Bobbie-Jo Webb-Robertson, Kathleen Waugh, Marian J Rewers, Qibin Zhang
Blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n=11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n=10)...
October 6, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28993191/the-anti-aging-protein-klotho-is-induced-by-gaba-therapy-and-exerts-protective-and-stimulatory-effects-on-pancreatic-beta-cells
#18
Gérald J Prud'homme, Yelena Glinka, Merve Kurt, Wenjuan Liu, Qinghua Wang
Systemic gamma-aminobutyric acid (GABA) therapy prevents or ameliorates type 1 diabetes (T1D), by suppressing autoimmune responses and stimulating pancreatic beta cells. In beta cells, it increases insulin secretion, prevents apoptosis, and induces regeneration. It is unclear how GABA mediates these effects. We hypothesized that Klotho is involved. It is a multi-functional protein expressed in the kidneys, brain, pancreatic beta cells, other tissues, and is cell-bound or soluble. Klotho knockout mice display accelerated aging, and in humans Klotho circulating levels decline with age, renal disease and diabetes...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28991371/protective-effects-of-dietary-polyphenols-from-black-soybeans-seed-coats-on-the-islet-and-renal-function-in-a-streptozotocin-induced-diabetic-rats
#19
Ju Qiu, Hong Zhu, Peng Liu, Jing Wang, Lingang Lu
BACKGROUND: The aim is to investigate the anti-diabetic effects of a crude polyphenols extract (BSCP) from black soybeans seed coats (BSC) and the BSC whole flour, and illustrate the mechanism in terms of islet and renal protection. RESULTS: The BSCP and BSC effectively controlled the increased blood glucose level and the impaired glucose tolerance in streptozotocin (STZ) induced diabetic rats after 8-week treatment. They increased the concentrations of serum insulin, C-peptide, and Glp-1 (P < 0...
October 9, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28991267/cytotoxic-and-regulatory-roles-of-mucosal-associated-invariant-t-cells-in-type-1-diabetes
#20
Ophélie Rouxel, Jennifer Da Silva, Lucie Beaudoin, Isabelle Nel, Céline Tard, Lucie Cagninacci, Badr Kiaf, Masaya Oshima, Marc Diedisheim, Marion Salou, Alexandra Corbett, Jamie Rossjohn, James McCluskey, Raphael Scharfmann, Manuela Battaglia, Michel Polak, Olivier Lantz, Jacques Beltrand, Agnès Lehuen
Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic β-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I-related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes...
October 9, 2017: Nature Immunology
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