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https://www.readbyqxmd.com/read/28430907/food-intake-affects-sperm-egg-fusion-through-the-gip-psg17-axis-in-mice
#1
Tatsunori Shimizu, Takehiro Sato, Katsushi Tsukiyama, Hiroki Fujita, Shunsuke Kato, Manabu Hoizumi, Hiromitsu Shirasawa, Takuma Narita, Yukihiro Terada, Yutaka Seino, Yuichiro Yamada
In addition to overeating, starvation also reduces fecundity in mammals. However, little is known about the molecular mechanisms linking food intake to fertility, especially in males. Gastric inhibitory polypeptide (GIP), which is released from intestinal K-cells after meal ingestion, stimulates insulin secretion from pancreatic β-cells through the action of incretin and has several extra-pancreatic effects. Here, we identified GIP receptor (Gipr) expression in mouse spermatids. Microarray analysis revealed that pregnancy-specific glycoprotein 17 (Psg17), a potential CD9-binding partner, was significantly decreased in GIP receptor-knockout (Gipr-/-) testes...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430139/the-metalloproteinase-adam28-promotes-metabolic-dysfunction-in-mice
#2
Lakshini Herat, Caroline Rudnicka, Yasunori Okada, Satsuki Mochizuki, Markus Schlaich, Vance Matthews
Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28429777/interleukin-6-increases-the-expression-and-activity-of-insulin-degrading-enzyme
#3
Mirian A Kurauti, José M Costa-Júnior, Sandra M Ferreira, Gustavo J Santos, Carlos H G Sponton, Everardo M Carneiro, Guilherme D Telles, Mara P T Chacon-Mikahil, Cláudia R Cavaglieri, Luiz F Rezende, Antonio C Boschero
Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429615/regulation-of-vascular-large-conductance-calcium-activated-potassium-channels-by-nrf2-signalling
#4
Yong Li, Xiao-Li Wang, Xiaojing Sun, Qiang Chai, Jingchao Li, Benjamin Thompson, Win-Kuang Shen, Tong Lu, Hon-Chi Lee
BK channels are major ionic determinants of vasodilation. BK channel function is impaired in diabetic vessels due to accelerated proteolysis of its beta-1 (BK-β1) subunits in response to increased oxidative stress. The nuclear factor E2-related factor-2 (Nrf2) signalling pathway has emerged as a master regulator of cellular redox status, and we hypothesized that it plays a central role in regulating BK channel function in diabetic vessels. We found that Nrf2 expression was markedly reduced in db/db diabetic mouse aortas, and this was associated with significant downregulation of BK-β1...
April 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28428052/opening-eyes-to-nanomedicine-where-we-are-challenges-and-expectations-on-nanotherapy-for-diabetic-retinopathy
#5
REVIEW
Elisa J Campos, António Campos, João Martins, António Francisco Ambrósio
People affected with ocular diseases will significantly increase over the next decades, and, consequently, a substantial increase in health costs is expected. Diabetic retinopathy is the most common chronic complication of diabetes. The treatment of eye diseases affecting the posterior segment, such as diabetic retinopathy, is quite challenging due to the anatomy, physiology and biochemistry of the eye. Therefore, the development of new therapeutics for posterior eye diseases has been a major focus of pharmaceutical research in the area of vision sciences...
April 17, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28427075/diabetic-macular-edema-emerging-strategies-and-treatment-algorithms
#6
Elad Moisseiev, Anat Loewenstein
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients, and its management is often a long process requiring frequent monitoring and therapeutic interventions. During the past several decades, numerous treatments have been developed for the treatment of DME. Although many of them have been found to be effective and safe, there is relatively little comparative data, and no established guidelines for the optimal treatment approach exist. In this chapter, the evolution of DME therapies is reviewed, and the current common practice patterns are discussed...
2017: Developments in Ophthalmology
https://www.readbyqxmd.com/read/28422118/nutrient-regulation-of-%C3%AE-cell-function-what-do-islet-cell-animal-studies-tell-us
#7
REVIEW
R Carlessi, K N Keane, C Mamotte, P Newsholme
Diabetes mellitus is widely recognised as one of the most serious metabolic diseases worldwide, and its incidence in Asian countries is growing at an alarming rate. Type 2 diabetes (T2DM) is closely associated with age, sedentary lifestyle and poor diet. In T2DM, β-cell dysfunction will occur before hyperglycaemia develops. Excessive levels of glucose, lipid and various inflammatory factors interact at the level of the pancreatic islet to promote β-cell dysfunction. Pancreatic β-cell lines have been widely utilised since the early 1980s and have contributed a large volume of important information regarding molecular, metabolic and genetic mechanisms that regulate insulin secretion...
April 19, 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28421037/lipid-processing-in-the-brain-a-key-regulator-of-systemic-metabolism
#8
REVIEW
Kimberley D Bruce, Andrea Zsombok, Robert H Eckel
Metabolic disorders, particularly aberrations in lipid homeostasis, such as obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest together as the metabolic syndrome (MetS). Despite major advances in our understanding of the pathogenesis of these disorders, the prevalence of the MetS continues to rise. It is becoming increasingly apparent that intermediary metabolism within the central nervous system is a major contributor to the regulation of systemic metabolism. In particular, lipid metabolism within the brain is tightly regulated to maintain neuronal structure and function and may signal nutrient status to modulate metabolism in key peripheral tissues such as the liver...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28419197/inhibition-of-sarcolemmal-fat-cd36-by-sulfo-n-succinimidyl-oleate-rapidly-corrects-metabolism-and-restores-function-in-the-diabetic-heart-following-hypoxia-reoxygenation
#9
Latt S Mansor, Maria da Luz Sousa Fialho, Georgina Yea, Will A Coumans, James A West, Matthew Kerr, Carolyn A Carr, Joost J F P Luiken, Jan F C Glatz, Rhys D Evans, Julian L Griffin, Damian J Tyler, Kieran Clarke, Lisa C Heather
Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28416135/all-the-rage-in-lung-disease-the-receptor-for-advanced-glycation-endproducts-rage-is-a-major-mediator-of-pulmonary-inflammatory-responses
#10
REVIEW
Elizabeth A Oczypok, Timothy N Perkins, Tim D Oury
The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory pattern recognition receptor (PRR) that has been implicated in the pathogenesis of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells and was named for its ability to bind advanced glycation endproducts and promote vascular inflammation in the vessels of patients with diabetes. Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE's role in the lung...
March 18, 2017: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28410495/local-induction-of-lymphangiogenesis-with-engineered-fibrin-binding-vegf-c-promotes-wound-healing-by-increasing-immune-cell-trafficking-and-matrix-remodeling
#11
Esra Güç, Priscilla S Briquez, Didier Foretay, Manuel A Fankhauser, Jeffrey A Hubbell, Witold W Kilarski, Melody A Swartz
Lymphangiogenesis occurs in inflammation and wound healing, yet its functional roles in these processes are not fully understood. Consequently, clinically relevant strategies for therapeutic lymphangiogenesis remain underdeveloped, particularly using growth factors. To achieve controlled, local capillary lymphangiogenesis with protein engineering and determine its effects on fluid clearance, leukocyte trafficking, and wound healing, we developed a fibrin-binding variant of vascular endothelial growth factor C (FB-VEGF-C) that is slowly released upon demand from infiltrating cells...
March 25, 2017: Biomaterials
https://www.readbyqxmd.com/read/28409999/histone-hist1h1c-h1-2-regulates-autophagy-in-the-development-of-diabetic-retinopathy
#12
Wenjun Wang, Qing Wang, Danyang Wan, Yue Sun, Lin Wang, Hong Chen, Chengyu Liu, Robert B Petersen, Jianshuang Li, Weili Xue, Ling Zheng, Kun Huang
Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line...
March 2, 2017: Autophagy
https://www.readbyqxmd.com/read/28409126/genomics-and-comparative-genomic-analyses-provide-insight-into-the-taxonomy-and-pathogenic-potential-of-novel-emmonsia-pathogens
#13
Ying Yang, Qiang Ye, Kang Li, Zongwei Li, Xiaochen Bo, Zhen Li, Yingchun Xu, Shengqi Wang, Peng Wang, Huipeng Chen, Junzhi Wang
Over the last 50 years, newly described species of Emmonsia-like fungi have been implicated globally as sources of systemic human mycosis (emmonsiosis). Their ability to convert into yeast-like cells capable of replication and extra-pulmonary dissemination during the course of infection differentiates them from classical Emmonsia species. Immunocompromised patients are at highest risk of emmonsiosis and exhibit high mortality rates. In order to investigate the molecular basis for pathogenicity of the newly described Emmonsia species, genomic sequencing and comparative genomic analyses of Emmonsia sp...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28405188/compound-19e-a-novel-glucokinase-activator-protects-against-cytokine-induced-beta-cell-apoptosis-in-ins-1-cells
#14
Yoon Sin Oh, Eunhui Seo, Kaapjoo Park, Hee-Sook Jun
Previously, compound 19e, a novel heteroaryl-containing benzamide derivative, was identified as a potent glucokinase activator (GKA) and showed a glucose-lowering effect in diabetic mice. In this study, the anti-apoptotic actions of 19e were evaluated in INS-1 pancreatic beta-cells co-treated with TNF-α and IL-1β to induce cell death. Compound 19e protected INS-1 cells from cytokine-induced cell death, and the effect was similar to treatment with another GKA or exendin-4. Compound 19e reduced annexin-V stained cells and the expression of cleaved caspase-3 and poly (ADP-ribose) polymerase protein, as well as upregulated the expression of B-cell lymphoma-2 protein...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28403787/role-of-tissue-renin-angiotensin-system-and-the-chymase-angiotensin-1-12-axis-in-the-pathogenesis-of-diabetic-retinopathy
#15
Mohammad Shamsul Ola, Abdullah S Alhomida, Carlos M Ferrario, Sarfaraz Ahmad
Diabetic retinopathy (DR) is a major diabetes complication and the leading cause for vision loss and blindness in the adult human population. Diabetes, being an endocrinological disorder dysregulate a number of hormonal systems including the renin angiotensin system (RAS), which thereby may damage both vascular and neuronal cells in the retina. Angiotensin II (Ang II), an active component of the RAS is increased in diabetic retina, and may play a significant role in neurovascular damage leading to the progression of DR...
April 7, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28396983/the-islet-endothelial-cell-a-novel-contributor-to-beta-cell-secretory-dysfunction-in-diabetes
#16
REVIEW
Meghan F Hogan, Rebecca L Hull
The pancreatic islet is highly vascularised, with an extensive capillary network. In addition to providing nutrients and oxygen to islet endocrine cells and transporting hormones to the peripheral circulation, islet capillaries (comprised primarily of islet endothelial cells) are an important source of signals that enhance survival and function of the islet beta cell. In type 2 diabetes, and animal models thereof, evidence exists of morphological and functional abnormalities in these islet endothelial cells...
April 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28395252/a-glucose-sensitive-block-glycopolymer-hydrogel-based-on-dynamic-boronic-ester-bonds-for-insulin-delivery
#17
Baoqi Cai, Yanping Luo, Qianqian Guo, Xinge Zhang, Zhongming Wu
Hydrogels are good candidates to satisfy many needs for functional and tunable biomaterials. How to precisely control the gel structure and functions is crucial for the construction of sophisticated soft biomaterials comprising the hydrogels, which facilitates the impact of the surrounding environment on a unique biological function occurring. Here, glucose-responsive hydrogels comprised of 3-acrylamidophenyl boronic acid copolymerized with 2-lactobionamidoethyl methacrylate (p(APBA-b-LAMA)) were synthesized, and further evaluated as carriers for insulin delivery...
April 6, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28391065/novel-lipoproteoplex-delivers-keap1-sirna-based-gene-therapy-to-accelerate-diabetic-wound-healing
#18
Piul S Rabbani, Anna Zhou, Zachary M Borab, Joseph A Frezzo, Nikita Srivastava, Haresh T More, William J Rifkin, Joshua A David, Samuel J Berens, Raymond Chen, Sophia Hameedi, Muhammad H Junejo, Camille Kim, Rita A Sartor, Che F Liu, Pierre B Saadeh, Jin K Montclare, Daniel J Ceradini
Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC)...
April 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28390093/understanding-the-role-of-the-gut-ecosystem-in-diabetes-mellitus
#19
REVIEW
Wanping Aw, Shinji Fukuda
Diabetes mellitus is a type of metabolic disorder patients are unable to regulate glycemia. It is currently worldwide public health issue and is a burden to society due to its disabling and common complications. Diabetes is multi-factorial and also induces the onset of other diseases. In this report, we will review the labyrinth encompassing the gut microbiota and gut microbiota derived metabolites on type 1 diabetes and type 2 diabetes pathogenesis. There has been exceptional improvements in Deoxyribonucleic acid (DNA) sequencing and mass spectrometry technologies throughout these years and this has allowed the comprehensive collection of information on our unique gut ecosystem...
April 8, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28389215/clock-gene-dysregulation-induced-by-chronic-er-stress-disrupts-%C3%AE-cell-function
#20
Yasuharu Ohta, Akihiko Taguchi, Takuro Matsumura, Hiroko Nakabayashi, Masaru Akiyama, Kaoru Yamamoto, Ruriko Fujimoto, Risa Suetomi, Akie Yanai, Koh Shinoda, Yukio Tanizawa
In Wfs1(-/-)A(y)/a islets, in association with endoplasmic reticulum (ER) stress, D-site-binding protein (Dbp) expression decreased and Nuclear Factor IL-3 (Nfil3)/E4 Promoter-binding protein 4 (E4bp4) expression increased, leading to reduced DBP transcriptional activity. Similar alterations were observed with chemically-induced ER stress. Transgenic mice expressing E4BP4 under the control of the mouse insulin I gene promoter (MIP), in which E4BP4 in β-cells is expected to compete with DBP for D-box, displayed remarkable glucose intolerance with severely impaired insulin secretion...
March 30, 2017: EBioMedicine
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