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Diabetes

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https://www.readbyqxmd.com/read/27913577/metabolite-profiling-of-lada-challenges-the-view-of-a-metabolically-distinct-subtype
#1
Mahmoud Al-Majdoub, Arslan Ali, Petter Storm, Anders Rosengren, Leif Groop, Peter Spégel
Latent autoimmune diabetes in adults (LADA) usually refers to GADAb positive diabetes with onset after 35 years of age and no insulin treatment within the first 6 months after diagnosis. However, it is not always easy to distinguish LADA from type 1 or type 2 diabetes.In this study we examined whether metabolite profiling could help to distinguish LADA (N=50) from type 1 (N=50) and type 2 diabetes (N=50).Out of 123 identified metabolites, 99 differed between the diabetes types. However, no unique metabolite profile could be identified for any of the types...
December 2, 2016: Diabetes
https://www.readbyqxmd.com/read/27908917/erratum-impact-of-perturbed-pancreatic-%C3%AE-cell-cholesterol-homeostasis-on-adipose-tissue-and-skeletal-muscle-metabolism-diabetes-2016-65-3610-3620
#2
Blake J Cochran, Liming Hou, Anil Paul Chirackal Manavalan, Benjamin M Moore, Fatiha Tabet, Afroza Sultana, Luisa Cuesta Torres, Shudi Tang, Sudichhya Shrestha, Praween Senanayake, Mili Patel, William J Ryder, Andre Bongers, Marie Maraninchi, Valerie C Wasinger, Marit Westerterp, Alan R Tall, Philip J Barter, Kerry-Anne Rye
No abstract text is available yet for this article.
December 1, 2016: Diabetes
https://www.readbyqxmd.com/read/27908916/erratum-functional-brain-networks-are-altered-in-type-2-diabetes-and-prediabetes-signs-for-compensation-of-cognitive-decrements-the-maastricht-study-diabetes-2016-65-2404-2413
#3
Frank C G van Bussel, Walter H Backes, Tamar M van Veenendaal, Paul A M Hofman, Martin P J van Boxtel, Miranda T Schram, Simone J S Sep, Pieter C Dagnelie, Nicolaas Schaper, Coen D A Stehouwer, Joachim E Wildberger, Jacobus F A Jansen
No abstract text is available yet for this article.
December 1, 2016: Diabetes
https://www.readbyqxmd.com/read/27908915/-the-hypothalamic-glucagon-like-peptide-1-glp-1-receptor-glp-1r-is-sufficient-but-not-necessary-for-the-regulation-of-energy-balance-and-glucose-homeostasis-in-mice
#4
Melissa A Burmeister, Jennifer E Ayala, Hannah Smouse, Adriana Landivar-Rocha, Jacob D Brown, Daniel J Drucker, Doris A Stoffers, Darleen A Sandoval, Randy J Seeley, Julio E Ayala
Pharmacological activation of the hypothalamic glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) promotes weight loss and improves glucose tolerance. This demonstrates that the hypothalamic GLP-1R is sufficient but does not show whether it is necessary for the effects of exogenous GLP-1R agonists (GLP-1RA) or endogenous GLP-1 on these parameters. To address this, we crossed mice harboring floxed Glp1r alleles to mice expressing Nkx2.1-Cre to knock down Glp1r expression throughout the hypothalamus (GLP-1RKD(ΔNkx2...
December 1, 2016: Diabetes
https://www.readbyqxmd.com/read/27903748/hepatic-expression-of-adenovirus-36-e4orf1-improves-glycemic-control-and-promotes-glucose-metabolism-via-akt-activation
#5
Travis B McMurphy, Wei Huang, Run Xiao, Xianglan Liu, Nikhil V Dhurandhar, Lei Cao
Considering that impaired proximal insulin signaling is linked with diabetes, approaches that enhance glucose disposal independent of insulin signaling are attractive. In vitro data indicate that the E4ORF1 peptide derived from human adenovirus 36 (Ad36) interacts with cells from adipose tissue, skeletal muscle and liver to enhance glucose disposal, independent of proximal insulin signaling. Adipocyte-specific expression of Ad36E4ORF1 improved hyperglycemia in mice. To determine the hepatic interaction of Ad36E4ORF1 in enhancing glycemic control, we expressed E4ORF1 of Ad36 or adenovirus 5, or fluorescent tag alone using recombinant adeno-associated viral vector in the livers of three mouse models...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903747/improved-glucose-homeostasis-in-obese-mice-treated-with-resveratrol-is-associated-with-alterations-in-the-gut-microbiome
#6
Miranda M Sung, Ty T Kim, Emmanuel Denou, Carrie-Lynn M Soltys, Shereen M Hamza, Nikole J Byrne, Grant Masson, Heekuk Park, David S Wishart, Karen L Madsen, Jonathan D Schertzer, Jason R B Dyck
Oral administration of resveratrol is able to improve glucose homeostasis in obese individuals. Herein we show that resveratrol ingestion produces taxonomic and predicted functional changes in the gut microbiome of obese mice. In particular, changes in the gut microbiome were characterized by a decreased relative abundance of Turicibacteraceae, Moryella, Lachnospiraceae, and Akkermansia and increased relative abundance of Bacteroides and Parabacteroides Moreover, fecal transfer from healthy resveratrol-fed donor mice is sufficient to improve glucose homeostasis in obese mice, suggesting that the resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903746/intestinal-glycolysis-visualized-by-fdg-pet-ct-correlates-with-glucose-decrement-after-gastrectomy
#7
Cheol Ryong Ku, Narae Lee, Jae Won Hong, In Gyu Kwon, Woo Jin Hyung, Sung Hoon Noh, Eun Jig Lee, Mijin Yun, Arthur Cho
Gastrectomy method is known to influence glucose homeostasis. (18)F-fluorodeoxyglucose (FDG) PET/CT acquired after gastrectomy often reveals newly developed physiologic small bowel uptake. We correlated newly developed small bowel FDG uptake and glucose homeostasis in post-gastrectomy gastric cancer patients. We retrospectively analyzed 239 non-diabetic patients who underwent staging and follow-up FDG PET/CT before and after gastrectomy for gastric cancer. Post-operative small bowel glycolysis was quantified by recording intestinal total lesion glycolysis (TLG)...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903745/inhibiting-microglia-expansion-prevents-diet-induced-hypothalamic-and-peripheral-inflammation
#8
Caroline André, Omar Guzman-Quevedo, Charlotte Rey, Julie Rémus-Borel, Samantha Clark, Ashley Castellanos-Jankiewicz, Elodie Ladeveze, Thierry Leste-Lasserre, Agnes Nadjar, Djoher Nora Abrous, Sophie Laye, Daniela Cota
Cell proliferation and neuroinflammation in the adult hypothalamus may contribute to the pathogenesis of obesity. Here we tested whether the intertwining of these two processes has a role in the metabolic changes caused by three weeks of saturated high-fat diet (HFD) consumption.As compared to chow, HFD-fed mice rapidly increased body weight and fat mass, and specifically showed increased microglia number in the arcuate nucleus (ARC) of the hypothalamus. Microglia expansion required the adequate presence of fats and carbohydrates in the diet, since feeding mice a very high-fat, very low-carbohydrate diet did not affect cell proliferation...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27903744/metallothionein-is-downstream-of-nrf2-and-partially-mediates-sulforaphane-prevention-of-diabetic-cardiomyopathy
#9
Junlian Gu, Yanli Cheng, Hao Wu, Lili Kong, Shudong Wang, Zheng Xu, Zhiguo Zhang, Yi Tan, Bradley B Keller, Honglan Zhou, Yuehui Wang, Zhonggao Xu, Lu Cai
We have reported that sulforaphane prevented diabetic cardiomyopathy in both T1DM and T2DM animal models via the up-regulation of Nrf2 and metallothionein (MT). Here we tested whether sulforaphane protects the heart from T2DM directly through Nrf2, MT or both. Using Nrf2-knockout (KO), MT-KO, and wild-type mice T2DM was induced by feeding high-fat diet (HFD) for 3 months followed by a small dose of streptozotocin. Age-matched controls were given normal diet (ND). Both T2DM and control mice were then treated with or without sulforaphane for 4 months with continually feeding HFD or ND...
November 30, 2016: Diabetes
https://www.readbyqxmd.com/read/27899487/glomerular-endothelial-mitochondrial-dysfunction-is-essential-and-characteristic-of-diabetic-kidney-disease-susceptibility
#10
Ilse Daehn, Haiying Qi, Gabriella Casalena, Shaolin Shi, Liping Yu, Kerstin Ebefors, Yezhou Sun, Weijia Zhang, Vivette D'Agati, Detlef Schlondorff, Börje Haraldsson, Erwin Böttinger
The molecular signaling mechanisms between glomerular cell types during initiation/progression of diabetic kidney disease (DKD) remain poorly understood. We compared the early transcriptome profile between DKD resistant C57BL/6J (B6) and DKD susceptible DBA/2J (D2) glomeruli, and demonstrated a significant down regulation of essential mitochondrial genes in glomeruli from diabetic D2 mice, but not in B6 with comparable hyperglycemia. Diabetic D2 mice manifested increased mtDNA lesions (8-oxoG), exclusively localized to glomerular endothelial cells after 3 weeks of diabetes and these accumulated over time as well as increased urine secretion of 8-oxodG...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899486/functional-investigations-of-hnf1a-identify-rare-variants-as-risk-factors-for-type-2-diabetes-in-the-general-population
#11
Laeya Abdoli Najmi, Ingvild Aukrust, Jason Flannick, Janne Molnes, Noel Burtt, Anders Molven, Leif Groop, David Altshuler, Stefan Johansson, Lise Bjørkhaug, Pål Rasmus Njølstad
Variants in HNF1A encoding hepatocyte nuclear factor-1A are associated with maturity-onset diabetes of the young (MODY3) and type 2 diabetes. We investigated whether functional classification of HNF1A rare coding variants can inform models of diabetes risk prediction in the general population by analyzing the effect of 27 HNF1A variants identified in well-phenotyped populations (n = 4115). Bioinformatics tools classified 11 variants as likely pathogenic and showed no association with diabetes risk (combined MAF = 0...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899485/circulating-microrna-122-is-associated-with-the-risk-of-new-onset-metabolic-syndrome-and-type-2-diabetes
#12
Peter Willeit, Philipp Skroblin, Alexander R Moschen, Xiaoke Yin, Dorothee Kaudewitz, Anna Zampetaki, Temo Barwari, Meredith Whitehead, Cristina M Ramírez, Leigh Goedeke, Noemi Rotllan, Enzo Bonora, Alun D Hughes, Peter Santer, Carlos Fernández-Hernando, Herbert Tilg, Johann Willeit, Stefan Kiechl, Manuel Mayr
MicroRNA-122 (miR-122) is abundant in the liver and involved in lipid homeostasis, but its relevance to the long-term risk of developing metabolic disorders is unknown. We therefore measured circulating miR-122 in the prospective population-based Bruneck Study (n=810; survey year: 1995). Circulating miR-122 was associated with prevalent insulin resistance, obesity, metabolic syndrome, type-2 diabetes, and an adverse lipid profile. Among 92 plasma proteins and 135 lipid subspecies quantified with mass spectrometry, it correlated inversely with zinc-alpha-2-glycoprotein and positively with afamin, complement-factor H, VLDL-associated apolipoproteins, and lipid subspecies containing monounsaturated and saturated fatty acids...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899484/lack-of-cul4b-in-adipocytes-promotes-ppar%C3%AE-mediated-adipose-tissue-expansion-and-insulin-sensitivity
#13
Peishan Li, Yu Song, Wenying Zan, Liping Qin, Shuang Han, Baichun Jiang, Hao Dou, Changshun Shao, Yaoqin Gong
Obesity and obesity-associated diseases are linked to dysregulation of peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. Identification of the factors that regulate PPARγ expression and activity is crucial for combating obesity. However, the ubiquitin E3 ligases that target PPARγ for proteasomal degradation have been rarely identified and their functions in vivo have not been characterized. Here we report that CUL4B-RING E3 ligase (CRL4B) negatively regulates PPARγ by promoting its polyubiquitination and proteasomal degradation...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899483/integrin-linked-kinase-is-necessary-for-the-development-of-diet-induced-hepatic-insulin-resistance
#14
Ashley S Williams, Elijah Trefts, Louise Lantier, Carrie Grueter, Deanna P Bracy, Freyja D James, Ambra Pozzi, Roy Zent, David H Wasserman
The liver extracellular matrix (ECM) expands with high fat (HF) feeding. This finding led us to address whether receptors for the ECM, integrins, are key to the development of diet-induced hepatic insulin resistance. Integrin-linked kinase (ILK) is a downstream integrin signaling molecule involved in multiple hepatic processes including those related to differentiation, wound healing and metabolism. We tested the hypothesis that deletion of ILK in mice on a HF diet would disrupt the ECM-Integrin signaling axis thereby preventing the transformation into the insulin resistant liver...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899482/transient-receptor-potential-canonical-3-trpc3-channels-are-required-for-hypothalamic-glucose-detection-and-energy-homeostasis
#15
Chloé Chrétien, Claire Fenech, Fabienne Liénard, Sylvie Grall, Charlène Chevalier, Sylvie Chaudy, Xavier Brenachot, Raymond Berges, Katie Louche, Romana Stark, Emmanuelle Nédélec, Amélie Laderrière, Zane B Andrews, Alexandre Benani, Veit Flockerzi, Jean Gascuel, Jana Hartmann, Cédric Moro, Lutz Birnbaumer, Corinne Leloup, Luc Pénicaud, Xavier Fioramonti
The medio-basal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that Transient Receptor Potential Canonical type-3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis.To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mice models...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27899481/hznt8-slc30a8-transgenic-mice-which-overexpress-the-r325w-polymorph-have-reduced-islet-zn2-and-proinsulin-levels-increased-glucose-tolerance-after-a-high-fat-diet-and-altered-levels-of-pancreatic-zinc-binding-proteins
#16
Li Li, Shi Bai, Christian T Sheline
Zinc is involved in both type-1 (T1DM) and type-2 (T2DM) diabetes. The wildtype (WT) form of the beta-cell specific Zn(2+) transporter, ZNT8, is linked to T2DM susceptibility. ZnT8 null mice have a mild phenotype with a slight decrease in glucose tolerance, whereas patients with the ZnT8 R325W polymorphism (rs13266634) have decreased proinsulin staining and susceptibility to T2DM. We measured zinc, insulin, and proinsulin stainings, and IPGTT in transgenic mice overexpressing hZnT8 WT or hZnT8 R325W fed a normal or high fat diet (HFD)...
November 29, 2016: Diabetes
https://www.readbyqxmd.com/read/27872147/primary-human-and-rat-beta-cells-release-the-intracellular-autoantigens-gad65-ia-2-and-proinsulin-in-exosomes-together-with-cytokine-induced-enhancers-of-immunity
#17
Chiara Cianciaruso, Edward A Phelps, Miriella Pasquier, Romain Hamelin, Davide Demurtas, Mohamed Alibashe Ahmed, Lorenzo Piemonti, Sachiko Hirosue, Melody A Swartz, Michele De Palma, Jeffrey A Hubbell, Steinunn Baekkeskov
The target autoantigens in several organ-specific autoimmune diseases, including type 1 diabetes (T1D), are intracellular membrane proteins, whose initial encounter with the immune system is poorly understood. Here we propose a new model for how these proteins can initiate autoimmunity. We found that rat and human pancreatic islets release the intracellular β-cell autoantigens in human T1D, GAD65, IA-2 and proinsulin, in exosomes, which are taken up by and activate dendritic cells. Accordingly, anchoring of GAD65 to exosome-mimetic liposomes strongly boosted antigen presentation and T cell activation in the context of the human type 1 diabetes susceptibility haplotype HLA-DR4...
November 21, 2016: Diabetes
https://www.readbyqxmd.com/read/27864307/pancreatic-beta-cells-express-the-fetal-islet-hormone-gastrin-in-rodent-and-human-diabetes
#18
Tehila Dahan, Oren Ziv, Elad Horwitz, Hai Zemmour, Judith Lavi, Avital Swisa, Gil Leibowitz, Frances M Ashcroft, Peter In't Veld, Benjamin Glaser, Yuval Dor
Beta-cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of beta-cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. While in mice gastrin is expressed insulin+ cells, in humans with T2D gastrin expression occurs in both insulin+ and somatostatin+ cells. Genetic lineage tracing in mice indicates that gastrin expression is turned on in a subset of differentiated beta-cells following exposure to severe hyperglycemia...
November 18, 2016: Diabetes
https://www.readbyqxmd.com/read/27856609/ppar%C3%AE-is-required-for-exercise-to-attenuate-endoplasmic-reticulum-stress-and-endothelial-dysfunction-in-diabetic-mice
#19
Wai San Cheang, Wing Tak Wong, Lei Zhao, Jian Xu, Li Wang, Chi Wai Lau, Zhen Yu Chen, Ronald Ching Wan Ma, Aimin Xu, Nanping Wang, Xiao Yu Tian, Yu Huang
Physical activity has profound benefits on health especially cardiometablic wellness. Experiments on rodents with trained exercise showed that exercise improves vascular function and reduces vascular inflammation by modulating the balance between nitric oxide (NO) and oxidative stress. However, it is unclear what is the upstream regulator of exercise-induced vascular benefits. We aim to investigate the involvement of peroxisome proliferator-activated receptor δ (PPARδ) in exercise-induced vascular functional improvement...
November 17, 2016: Diabetes
https://www.readbyqxmd.com/read/27856608/reversal-of-bone-marrow-mobilopathy-and-enhanced-vascular-repair-by-angiotensin-1-7-in-diabetes
#20
Goutham Vasam, Shrinidh Joshi, Sean E Thatcher, Stephen H Bartelmez, Lisa A Cassis, Yagna Pr Jarajapu
Ang-(1-7)/MasR pathway activates vascular repair-relevant functions of bone marrow progenitor cells. We tested the effects of Ang-(1-7) on mobilization and vasoreparative functions of progenitor cells that are impaired in diabetes. Study was carried out in streptozotocin-induced diabetic or db/db mice. Diabetes resulted in decreased number of Lineage(-) Sca-1(+) c-Kit(+) (LSK) cells in the circulation, which was normalized by Ang-(1-7). Diabetes-induced depletion of LSK cells in the bone marrow was reversed by Ang-(1-7)...
November 17, 2016: Diabetes
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