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Diabetes

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https://www.readbyqxmd.com/read/28325854/the-effect-of-diabetes-on-cortical-function-in-stroke-implications-for-post-stroke-plasticity
#1
William Huynh, Natalie Kwai, Ria Arnold, Arun V Krishnan, Cindy S-Y Lin, Steve Vucic, Matthew C Kiernan
Diabetes may impair the capacity for neuroplasticity such that patients experience a slower and poorer recovery after stroke. The current study aimed to investigate changes in cortical function in stroke patients with diabetes to determine how this comorbidity may impact post-stroke cortical plasticity and thereby functional recovery. From a cohort of 57 participants, threshold-tracking transcranial magnetic stimulation was utilised to assess cortical function over the ipsi- and contralesional hemispheres in 7 diabetic patients following an acute stroke, and compared to 12 stroke patients without diabetes...
March 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28325853/deletion-of-macrophage-mineralocorticoid-receptor-protects-hepatic-steatosis-and-insulin-resistance-through-er%C3%AE-hgf-met-pathway
#2
Yu-Yao Zhang, Chao Li, Gao-Feng Yao, Lin-Juan Du, Yuan Liu, Xiao-Jun Zheng, Shuai Yan, Jian-Yong Sun, Yan Liu, Ming-Zhu Liu, Xiaoran Zhang, Gang Wei, Wenxin Tong, Xiaobei Chen, Yong Wu, Shuyang Sun, Suling Liu, Qiurong Ding, Ying Yu, Huiyong Yin, Sheng-Zhong Duan
Although the importance of macrophages in nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) has been recognized, it remains elusive how macrophages impact hepatocytes. Mineralocorticoid receptor (MR) has been implied to play important roles in NAFLD and T2DM. However, cellular and molecular mechanisms are largely unknown. Here we report that myeloid MR knockout (MRKO) improves glucose intolerance, insulin resistance, and hepatic steatosis in obese mice. Estrogen signaling is sufficient and necessary for such improvements...
March 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28302654/palmitate-induced-vacuolar-type-h-atpase-inhibition-feeds-forward-into-insulin-resistance-and-contractile-dysfunction
#3
Yilin Liu, Laura K M Steinbusch, Miranda Nabben, Dimitris Kapsokalyvas, Marc van Zandvoort, Patrick Schönleitner, Gudrun Antoons, Peter J Simons, Will A Coumans, Amber Geomini, Dipanjan Chanda, Jan F C Glatz, Dietbert Neumann, Joost J F P Luiken
Dietary fat overconsumption leads to myocardial lipid accumulation through mechanisms that are incompletely resolved. Previously, we identified increased translocation of the fatty acid transporter CD36 from its endosomal storage compartment to the sarcolemma as primary mechanism of excessive myocellular lipid import. Here, we show that increased CD36 translocation is caused by alkalinization of endosomes due to inhibition of proton pumping activity of vacuolar-type H(+)-ATPase (v-ATPase). Endosomal alkalinization was observed in hearts from rats fed a lard-based high fat-diet and in rodent and human cardiomyocytes upon palmitate overexposure, and appeared as early lipid-induced event preceding the onset of insulin resistance...
March 16, 2017: Diabetes
https://www.readbyqxmd.com/read/28292969/exercise-increases-human-skeletal-muscle-insulin-sensitivity-via-coordinated-increases-in-microvascular-perfusion-and-molecular-signaling
#4
Kim A Sjøberg, Christian Frøsig, Rasmus Kjøbsted, Lykke Sylow, Maximilian Kleinert, Andrew C Betik, Christopher S Shaw, Bente Kiens, Jørgen F P Wojtaszewski, Stephen Rattigan, Erik A Richter, Glenn K McConell
Insulin resistance is a major health risk and although exercise clearly improves skeletal muscle insulin sensitivity, the mechanisms are unclear. Here we show that initiation of a euglycemic hyperinsulinemic clamp four hours after single-legged exercise in humans increased microvascular perfusion (determined by contrast enhanced ultrasound) by 65% in the exercised leg and 25% in the rested leg (p<0.05) and leg glucose uptake increased 50% more (p<0.05) in the exercised leg than the rested leg. Importantly, infusion of the nitric oxide synthase inhibitor L-NMMA into both femoral arteries reversed the insulin stimulated increase in microvascular perfusion in both legs and abrogated the greater glucose uptake in the exercised compared with the rested leg...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28292968/micu1-alleviates-diabetic-cardiomyopathy-through-mitochondrial-ca-2-dependent-antioxidant-response
#5
Lele Ji, Fengzhou Liu, Zhe Jing, Qichao Huang, Ya Zhao, Haiyan Cao, Jun Li, Chun Yin, Jinliang Xing, Fei Li
Diabetic cardiomyopathy is a major cause of mortality in diabetic patients, but specific strategies for prevention or treatment of diabetic cardiomyopathy have not been clarified yet. MICU1 is a key regulator of mitochondria Ca(2+) uptake, which plays important roles in regulating mitochondrial oxidative phosphorylation and redox balance. However, to date, the significance of MICU1 in diabetic hearts has never been investigated. Here, we demonstrated that MICU1 was downregulated in db/db mouse heart, which contributes to myocardial apoptosis in diabetes...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28292967/pik3r1-is-required-for-glucocorticoid-induced-perilipin-1-phosphorylation-in-lipid-droplet-for-adipocyte-lipolysis
#6
Taiyi Kuo, Tzu-Chieh Chen, Rebecca A Lee, Nguyen Huynh Thao Nguyen, Augusta E Broughton, Danyun Zhang, Jen-Chywan Wang
Glucocorticoids promote lipolysis in white adipose tissue (WAT) to adapt to energy demands under stress, while superfluous lipolysis causes metabolic disorders, including dyslipidemia and hepatic steatosis. Glucocorticoid-induced lipolysis requires the phosphorylation of cytosolic hormone sensitive lipase (HSL) and perilipin 1 (Plin1) in the lipid droplet by protein kinase A (PKA). We previously identified Pik3r1 (a.k.a. p85α) as a glucocorticoid receptor target gene. Here, we found that glucocorticoids increased HSL phosphorylation, but not Plin1 phosphorylation, in adipose tissue-specific Pik3r1-null (AKO) mice...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28292966/endothelial-hif-1%C3%AE-enables-hypothalamic-glucose-uptake-to-drive-pomc-neurons
#7
Luis Varela, Shigetomo Suyama, Yan Huang, Marya Shanabrough, Matthias H Tschoep, Xiao-Bing Gao, Frank J Giordano, Tamas L Horvath
Glucose is the primary driver of hypothalamic POMC neurons. Here, we show that endothelial HIF-1α controls glucose uptake in the hypothalamus, and, that it is up-regulated in conditions of under-nourishment during which POMC neuronal activity is decreased. Endothelium-specific knockdown of HIF-1α impairs the ability of POMC neurons to adapt to the changing metabolic environment in vivo resulting in overeating of mice after food deprivation. The impaired functioning of POMC neurons was reversed ex vivo or by parenchymal glucose administration...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28292965/repurposed-jak1-jak2-inhibitor-reverses-established-autoimmune-insulitis-in-non-obese-diabetic-mice
#8
Prerak M Trivedi, Kate L Graham, Nicholas A Scott, Misty R Jenkins, Suktilang Majaw, Robyn M Sutherland, Stacey Fynch, Andrew M Lew, Christopher J Burns, Balasubramanian Krishnamurthy, Thomas C Brodnicki, Stuart I Mannering, Thomas W Kay, Helen E Thomas
Recent advances in immunotherapeutics have not yet changed the routine management of autoimmune type 1 diabetes. There is an opportunity to repurpose therapeutics from other diseases to type 1 diabetes, especially when there is evidence for overlapping mechanisms. JAK1/JAK2 inhibitors are in development or clinical use for indications including rheumatoid arthritis. There is good evidence for activation of the JAK1/JAK2 and STAT1 pathway in human type 1 diabetes and in mouse models, especially in beta cells...
March 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28289043/exocytosis-mediated-urinary-full-length-megalin-excretion-is-linked-with-the-pathogenesis-of-diabetic-nephropathy
#9
Shankhajit De, Shoji Kuwahara, Michihiro Hosojima, Tomomi Ishikawa, Ryohei Kaseda, Piyali Sarkar, Yusuke Yoshioka, Hideyuki Kabasawa, Tomomichi Iida, Sawako Goto, Koji Toba, Yuki Higuchi, Yoshiki Suzuki, Masanori Hara, Hiroyuki Kurosawa, Ichiei Narita, Yoshiaki Hirayama, Takahiro Ochiya, Akihiko Saito
Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using enzyme-linked immunosorbent assay, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in T2DM patients...
March 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28279980/glucose-transporter-4-glut4-is-not-necessary-for-overload-induced-glucose-uptake-or-hypertrophic-growth-in-mouse-skeletal-muscle
#10
Shawna L McMillin, Denise L Schmidt, Barbara B Kahn, Carol A Witczak
Glucose transporter 4 (GLUT4) is necessary for acute insulin- and contraction-induced skeletal muscle glucose uptake, but its role in chronic muscle loading (overload)-induced glucose uptake is unknown. Our goal was to determine if GLUT4 is required for overload-induced glucose uptake. Overload was induced in mouse plantaris muscle by unilateral synergist ablation. After 5 days, muscle weights and ex vivo [(3)H]-2-deoxy-D-glucose uptake were assessed. Overload-induced muscle glucose uptake and hypertrophic growth were not impaired in muscle-specific GLUT4 knockout mice, demonstrating that GLUT4 is not necessary for these processes...
March 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28270523/id1-promotes-obesity-by-suppressing-brown-adipose-thermogenesis-and-white-adipose-browning
#11
Mallikarjun Patil, Bal Krishan Sharma, Sawsan Elattar, Judith Chang, Shweta Kapil, Jinling Yuan, Ande Satyanarayana
Obesity results from increased energy intake or defects in energy expenditure. Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. Peroxisome proliferator activated receptor γ coactivator 1α (PGC1α) controls BAT-mediated thermogenesis by regulating the expression of Ucp1 Inhibitor of differentiation 1 (Id1) is a helix-loop-helix transcription factor that plays important roles in cell proliferation and differentiation. Here, we demonstrate a novel function of Id1 in BAT thermogenesis and programming of beige adipocytes in white adipose tissue (WAT)...
March 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28270522/high-intensity-exercise-as-a-dishabituating-stimulus-restores-counterregulatory-responses-in-recurrently-hypoglycemic-rodents
#12
Alison D McNeilly, Jennifer R Gallagher, Jeffrey T-J Huang, Michael L J Ashford, Rory J McCrimmon
Hypoglycemia is a major adverse effect of insulin therapy for people with type 1 diabetes (T1D). Profound defects in the normal counterregulatory response to hypoglycemia explain the frequency of hypoglycemia occurrence in T1D. Defective counterregulation results to a large extent from prior exposure to hypoglycemia per se, leading to a condition called impaired awareness of hypoglycemia (IAH); the cause of which is unknown. In the present study, we investigate the hypothesis that IAH develops through a special type of adaptive memory referred to as habituation...
March 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28270521/pathogenic-role-of-microrna-21-in-diabetic-retinopathy-through-down-regulation-of-ppar%C3%AE
#13
Qian Chen, Fangfang Qiu, Kelu Zhou, H Greg Matlock, Yusuke Takahashi, Raju V S Rajala, Yanhui Yang, Elizabeth Moran, Jian-Xing Ma
Fenofibrate, a specific agonist of peroxisome proliferator-activated receptor alpha (PPARα), displays robust therapeutic effects on diabetic retinopathy (DR) in type 2 diabetic patients. Our recent studies have shown that PPARα is down-regulated in the diabetic retina, which contributes to the pathogenesis of DR. However, the mechanism for diabetes-induced down-regulation of PPARα remains unknown. We investigated the role of microRNA-21 (miR-21) in regulating PPARα in DR. MiR-21 was over-expressed, while PPARα levels were decreased in the retina of db/db mice, a type 2 diabetic model...
March 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28270520/functional-human-beige-adipocytes-from-induced-pluripotent-stem-cells
#14
Anne-Claire Guénantin, Nolwenn Briand, Emilie Capel, Florent Dumont, Romain Morichon, Claire Provost, Francesca Stillitano, Dorota Jeziorowska, Jean-Pierre Siffroi, Roger J Hajjar, Bruno Fève, Jean-Sébastien Hulot, Philippe Collas, Jacqueline Capeau, Corinne Vigouroux
Activation of thermogenic beige adipocytes has recently emerged as a promising therapeutic target in obesity and diabetes. Relevant human models for beige adipocyte differentiation are essential to implement such therapeutic strategies. We report a straightforward and efficient protocol to generate functional human beige adipocytes from induced pluripotent stem cells (hiPSCs). Without overexpression of exogenous adipogenic genes, our method recapitulates an adipogenic developmental pathway through successive mesodermal and adipogenic progenitor stages...
March 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28254844/vegf-a-expressing-adipose-tissue-shows-rapid-beiging-enhanced-survival-after-transplantation-and-confers-il4-independent-metabolic-improvements
#15
Jiyoung Park, Min Kim, Kai Sun, Yu Aaron An, Xue Gu, Philipp E Scherer
Adipocyte-derived VEGF-A plays a crucial role in angiogenesis and contributes to adipocyte function and systemic metabolism, such as insulin resistance, chronic inflammation and beigeing of subcutaneous adipose tissue. Utilizing a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpressing mouse model, we investigated the dynamics of local VEGF-A effects on tissue beiging of adipose tissue transplants. VEGF-A overexpression in adipocytes triggers angiogenesis. We also observe a rapid appearance of beige fat cells in subcutaneous white adipose tissue (sWATs) within as early as 2 days post induction of VEGF-A...
March 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28254843/genetics-of-type-2-diabetes-in-u-s-hispanic-latino-individuals-results-from-the-hispanic-community-health-study-study-of-latinos-hchs-sol
#16
Qibin Qi, Adrienne M Stilp, Tamar Sofer, Jee-Young Moon, Bertha Hidalgo, Adam A Szpiro, Tao Wang, Maggie C Y Ng, Xiuqing Guo, Yii-Der Ida Chen, Kent D Taylor, M Larissa Aviles-Santa, George Papanicolaou, James S Pankow, Neil Schneiderman, Cathy C Laurie, Jerome I Rotter, Robert C Kaplan
Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in US Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2499 T2D cases and 5247 controls from 6 Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance level. Conditional analysis on known index SNPs indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (OR=1...
March 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28254842/%C3%AE-cell-inactivation-of-gpr119-unmasks-incretin-dependence-of-gpr119-mediated-glucoregulation
#17
Brandon L Panaro, Grace B Flock, Jonathan E Campbell, Jacqueline L Beaudry, Xiemin Cao, Daniel J Drucker
GPR119 was originally identified as an orphan β-cell receptor however subsequent studies demonstrated that GPR119 also regulates β-cell function indirectly through incretin hormone secretion. We assessed the importance of GPR119 for β-cell function in Gpr119(-/-) mice and in newly generated Gpr119(βcell-/-) mice. Gpr119(-/-) mice displayed normal body weight and glucose tolerance on a regular chow diet. After high fat feeding, Gpr119(-/-) mice exhibited reduced fat mass, decreased levels of circulating adipokines, improved insulin sensitivity and better glucose tolerance...
March 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28250021/mast-cells-promote-seasonal-white-adipose-beiging-in-humans
#18
Brian S Finlin, Beibei Zhu, Amy L Confides, Philip M Westgate, Brianna D Harfmann, Esther E Dupont-Versteegden, Philip A Kern
Human subcutaneous white adipose tissue (SC WAT) increases the expression of beige adipocyte genes in the winter. Studies in rodents suggest that a number of immune mediators are important in the beiging response. Here we studied the seasonal beiging response in SC WAT from lean humans. We measured the gene expression of various immune cell markers and performed multivariate analysis of the gene expression data to identify genes that predict UCP1. IL4 and, unexpectedly, the mast cell marker CPA3 predicted UCP1 gene expression...
March 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28250020/fat-specific-sirt6-ablation-sensitizes-mice-to-high-fat-diet-induced-obesity-and-insulin-resistance-by-inhibiting-lipolysis
#19
Jiangying Kuang, Yuwei Zhang, Qinhui Liu, Jing Shen, Shiyun Pu, Shihai Cheng, Lei Chen, Hong Li, Tong Wu, Rui Li, Yanping Li, Min Zou, Zhiyong Zhang, Wei Jiang, Guoheng Xu, Aijuan Qu, Wen Xie, Jinhan He
Sirt6 is an NAD(+)-dependent deacetylase that is involved in the control of energy metabolism. However, the tissue-specific function of Sirt6 in the adipose tissue remains unknown. Here we showed that fat-specific Sirt6 knockout (FKO) sensitized mice to high-fat diet (HFD)-induced obesity, which was attributed to adipocyte hypertrophy rather than adipocyte hyperplasia. The adipocyte hypertrophy in FKO mice likely resulted from compromised lipolytic activity as an outcome of decreased expression of adipose triglyceride lipase (ATGL), a key lipolytic enzyme...
March 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28246295/autophagy-inhibits-the-accumulation-of-advanced-glycation-end-products-by-promoting-lysosomal-biogenesis-and-function-in-the-kidney-proximal-tubules
#20
Atsushi Takahashi, Yoshitsugu Takabatake, Tomonori Kimura, Ikuko Maejima, Tomoko Namba, Takeshi Yamamoto, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Tamotsu Yoshimori, Yoshitaka Isaka
Advanced glycation end products (AGEs) are involved in the progression of diabetic nephropathy. AGEs filtered by glomeruli or delivered from the circulation are endocytosed and degraded in the lysosomes of kidney proximal tubular epithelial cells (PTECs). Autophagy is a highly conserved degradation system which regulates intracellular homeostasis by engulfing cytoplasmic components. We have recently demonstrated that autophagic degradation of damaged lysosomes is indispensable for cellular homeostasis in some settings...
February 28, 2017: Diabetes
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