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Diabetes

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https://www.readbyqxmd.com/read/28729244/apoptosis-repressor-with-caspase-recruitment-domain-ameliorates-amyloid-induced-%C3%AE-cell-apoptosis-and-jnk-pathway-activation
#1
Andrew T Templin, Tanya Samarasekera, Daniel T Meier, Meghan F Hogan, Mahnaz Mellati, Michael T Crow, Richard N Kitsis, Sakeneh Zraika, Rebecca L Hull, Steven E Kahn
Islet amyloid is present in more than 90% of individuals with type 2 diabetes, where it contributes to β-cell apoptosis and insufficient insulin secretion. Apoptosis repressor with caspase recruitment domain (ARC) binds and inactivates components of the intrinsic and extrinsic apoptosis pathways, and was recently found to be expressed in islet β cells. Using a human islet amyloid polypeptide transgenic mouse model of islet amyloidosis, we show ARC knockdown increases amyloid-induced β-cell apoptosis and loss, while ARC overexpression decreases amyloid-induced apoptosis, thus preserving β cells...
July 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28724742/the-myokine-irisin-is-released-in-response-to-saturated-fatty-acids-and-promotes-pancreatic-beta-cell-survival-and-insulin-secretion
#2
Annalisa Natalicchio, Nicola Marrano, Giuseppina Biondi, Rosaria Spagnuolo, Rossella Labarbuta, Immacolata Porreca, Angelo Cignarelli, Marco Bugliani, Piero Marchetti, Sebastio Perrini, Luigi Laviola, Francesco Giorgino
This study explored the role of irisin as a new pancreatic beta-cell secretagogue and survival factor and its potential role in the communication between skeletal muscle and pancreatic beta-cells under lipotoxic conditions. Recombinant irisin stimulated insulin biosynthesis and glucose-stimulated insulin secretion (GSIS) in a PKA-dependent manner, and prevented saturated fatty acid-induced apoptosis in human and rat pancreatic beta-cells, as well as in human and murine pancreatic islets, via AKT/BCL2 signaling...
July 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28720696/persistent-organic-pollutants-impair-insulin-secretory-function-of-pancreatic-beta-cells-human-and-in-vitro-evidence
#3
Yu-Mi Lee, Chae-Myeong Ha, Se-A Kim, Themis Thoudam, Young-Ran Yoon, Dae-Jung Kim, Hyeon-Chang Kim, Hyo-Bang Moon, Sungmi Park, In-Kyu Lee, Duk-Hee Lee
Persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), have emerged as a new risk factor of type 2 diabetes (T2D). We evaluated whether chronic exposure to low-dose POPs affects insulin secretory function of beta-cells in humans and in vitro cells. Serum concentrations of OCPs and PCBs were measured in 200 nondiabetic adults. Mathematical-model-based insulin secretion indices were estimated using a 2-hour 7-sample oral glucose tolerance test. Insulin secretion by INS1E beta-cells was measured after 48-hour treatment with 3 OCPs or a PCB mixture...
July 18, 2017: Diabetes
https://www.readbyqxmd.com/read/28710139/hepatic-but-not-extra-hepatic-insulin-clearance-is-lower-in-african-american-than-in-european-american-women
#4
Francesca Piccinini, David C Polidori, Barbara A Gower, Richard N Bergman
African Americans (AA) tend to have higher plasma insulin concentrations than European Americans (EA); the increased insulin concentrations have been attributed to increased secretion and/or decreased insulin clearance by liver or other tissues. This work aims to characterize the contributions of hepatic versus extra-hepatic insulin degradation related to ethnic differences between AA versus EA. Using a recently-developed mathematical model employing insulin and C-peptide measurements from the insulin-modified frequently-sampled intravenous glucose tolerance test (FSIGT), we estimated hepatic vs...
July 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28710138/disruption-of-lipid-uptake-in-astroglia-exacerbates-diet-induced-obesity
#5
Yuanqing Gao, Clarita Layritz, Beata Legutko, Thomas O Eichmann, Elise Laperrousaz, Valentine S Moullé, Celine Cruciani-Guglielmacci, Christophe Magnan, Serge Luquet, Stephen C Woods, Robert H Eckel, Chun-Xia Yi, Cristina Garcia-Caceres, Matthias H Tschöp
Neuronal circuits in the brain help to control feeding behavior and systemic metabolism in response to afferent nutrient and hormonal signals. Although astrocytes have historically been assumed to be less relevant for such neuroendocrine control, we asked whether lipid uptake via lipoprotein lipase (LPL) in astrocytes is required for the central regulation of energy homeostasis. Ex vivo studies with hypothalamic-derived astrocytes showed that LPL expression is up-regulated by oleic acid; whereas it is decreased in response to palmitic acid or triglyceride...
July 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28705881/defining-a-novel-role-for-the-pdx1-transcription-factor-in-islet-%C3%AE-cell-maturation-and-proliferation-during-weaning
#6
Jason M Spaeth, Manisha Gupte, Mark Perelis, Yu-Ping Yang, Holly Cyphert, Shuangli Guo, Jin-Hua Liu, Min Guo, Joseph Bass, Mark A Magnuson, Christopher Wright, Roland Stein
The transcription factor encoded by the Pancreas Duodenum Homeobox-1 (Pdx1) gene is a critical transcriptional regulator, as it has fundamental actions in the formation of all pancreatic cell types, islet β cell development, and adult islet β cell function. Transgenic- and cell line-based experiments have identified 5'-flanking conserved sequences that control pancreatic and β cell-type-specific transcription, which are found within Area I (base pairs (bp) -2694 to -2561), II (bp -2139 to -1958), III (bp -1879 to -1799), and IV (bp -6200 to -5670)...
July 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28701334/genetic-susceptibility-change-in-physical-activity-and-long-term-weight-gain
#7
Tiange Wang, Tao Huang, Yoriko Heianza, Dianjianyi Sun, Yan Zheng, Wenjie Ma, Majken K Jensen, Jae H Kang, Janey L Wiggs, Louis R Pasquale, Eric B Rimm, JoAnn E Manson, Frank B Hu, Walter C Willett, Lu Qi
Whether change in physical activity over time modifies the genetic susceptibility to long-term weight gain is unknown. We calculated a body mass index (BMI)-genetic risk score (GRS) based on 77 BMI-associated single-nucleotide polymorphisms (SNPs) and a body fat percentage (BF%)-GRS based on 12 BF%-associated SNPs, respectively, in 9,390 women from the Nurses' Health Study (NHS) and 5,291 men from the Health Professionals Follow-up Study (HPFS). We analyzed the interactions between each GRS and change in physical activity on BMI/body weight change within five 4-year intervals from 1986 to 2006 using multivariable generalized linear models with repeated-measures analyses...
July 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28698262/thyroid-hormone-coordinates-pancreatic-islet-maturation-during-the-zebrafish-larval-to-juvenile-transition-to-maintain-glucose-homeostasis
#8
Hiroki Matsuda, Sri Teja Mullapudi, Yuxi Zhang, Daniel Hesselson, Didier Y R Stainier
Thyroid hormone (TH) signaling promotes tissue maturation and adult organ formation. Developmental transitions alter an organism's metabolic requirements, and it remains unclear how development and metabolic demands are coordinated. We used the zebrafish as a model to test whether and how TH signaling affects pancreatic islet maturation, and consequently glucose homeostasis, during the larval to juvenile transition. We found that exogenous TH precociously activates the β cell differentiation genes pax6b and mnx1, while downregulating arxa, a master regulator of α cell development and function...
July 11, 2017: Diabetes
https://www.readbyqxmd.com/read/28698261/adipocyte-specific-deficiency-of-de-novo-sphingolipid-biosynthesis-leads-to-lipodystrophy-and-insulin-resistance
#9
Su-Yeon Lee, Hui-Young Lee, Jae-Hwi Song, Goon-Tae Kim, Suwon Jeon, Yoo-Jeong Song, Jae Sung Lee, Jang-Ho Hur, Hyun Hee Oh, Shi-Young Park, Soon-Mi Shim, Hyun Joo Yoo, Byung Cheon Lee, Xian-Cheng Jiang, Cheol Soo Choi, Tae-Sik Park
Sphingolipids have been implicated in the etiology of chronic metabolic diseases. Here, we investigated whether sphingolipid biosynthesis is associated with the development of adipose tissues and metabolic diseases. SPTLC2, a subunit of serine palmitoyltransferase, was transcriptionally upregulated in the adipose tissues of obese mice and in differentiating adipocytes. Adipocyte-specific SPTLC2-deficient (aSPTLC2 KO) mice had markedly reduced adipose tissue mass. Fatty acids that were destined for the adipose tissue were instead shunted to liver and caused hepatosteatosis...
July 11, 2017: Diabetes
https://www.readbyqxmd.com/read/28696211/rab8a-deficiency-in-skeletal-muscle-causes-hyperlipidemia-and-hepatosteatosis-via-impairment-of-muscle-lipid-uptake-and-storage
#10
Qiaoli Chen, Ping Rong, Dijin Xu, Sangsang Zhu, Liang Chen, Bingxian Xie, Qian Du, Chao Quan, Yang Sheng, Tong-Jin Zhao, Peng Li, Hong Yu Wang, Shuai Chen
Skeletal muscle absorbs long chain fatty acids (LCFA) that are either oxidized in mitochondria or temporarily stored as triglycerides in lipid droplets (LDs). So far, it is still not fully understood how muscle lipid uptake and storage is regulated and whether it is important for whole-body lipid homeostasis. Here we show that the small GTPase Rab8a regulates muscle lipid uptake and storage in skeletal muscle. Muscle-specific Rab8a deletion caused hyperlipidemia and exacerbated high fat diet (HFD)-induced hepatosteatosis...
July 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28687706/bone-regulates-browning-and-energy-metabolism-through-mature-osteoblast-osteocyte-ppar%C3%AE-expression
#11
Julia Brun, Flavien Berthou, Mirko Trajkovski, Pierre Maechler, Michanlegelo Foti, Nicolas Bonnet
Peroxisome proliferator-activated receptor gamma (PPARγ) is a master regulator of energy metabolism. In bone it is known to regulate osteoblast differentiation and osteoclast activity. Whether PPARγ expression in bone cells, particularly osteocytes, regulates energy metabolism remains unknown. Here we show that mature osteoblast/osteocyte-specific ablation of PPARγ in mice (Ocy-PPARγ(-/-) ) alters body composition with age, namely less fat and more lean mass and enhances insulin sensitivity and energy expenditure compared to wildtype...
July 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28684635/a-type-2-diabetes-associated-functional-regulatory-variant-in-a-pancreatic-islet-enhancer-at-the-adcy5-locus
#12
Tamara S Roman, Maren E Cannon, Swarooparani Vadlamudi, Martin L Buchkovich, Brooke N Wolford, Ryan P Welch, Mario A Morken, Grace J Kwon, Arushi Varshney, Romy Kursawe, Ying Wu, Anne U Jackson, Michael R Erdos, Johanna Kuusisto, Markku Laakso, Laura J Scott, Michael Boehnke, Francis S Collins, Stephen C J Parker, Michael L Stitzel, Karen L Mohlke
Molecular mechanisms remain unknown for most type 2 diabetes genome-wide association study (GWAS) identified loci. Variants associated with type 2 diabetes and fasting glucose levels reside in introns of ADCY5, a gene that encodes adenylate cyclase 5. Adenylate cyclase 5 catalyzes the production of cyclic AMP, which is a second messenger molecule involved in cell signaling and pancreatic beta cell insulin secretion. We demonstrated that type 2 diabetes risk alleles are associated with decreased ADCY5 expression in human islets and examined candidate variants for regulatory function...
July 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28684634/the-effect-of-ingested-glucose-dose-on-the-suppression-of-endogenous-glucose-production-in-humans
#13
Greg M Kowalski, Samantha M Moore, Steven Hamley, Ahrathy Selathurai, Clinton R Bruce
Insulin clamp studies have shown that insulin's suppressive actions on endogenous glucose production (EGP) are markedly more sensitive than that for stimulating glucose disposal (Rd). However, clamp conditions do not adequately mimic postprandial physiological responses. Here, in healthy subjects, using the variable infusion dual-tracer approach, we used a 3-fold range of ingested glucose doses (25, 50 and 75 g) to investigate how physiologic changes in plasma insulin influence EGP. Remarkably, the glucose responses were similar for all doses tested, yet there was a dose-dependent increase in insulin secretion and plasma insulin levels...
July 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28679628/recruitment-of-epac2a-to-insulin-granule-docking-sites-regulates-priming-for-exocytosis
#14
Ida Alenkvist, Nikhil R Gandasi, Sebastian Barg, Anders Tengholm
Epac is a cAMP-activated guanine nucleotide exchange factor that mediates cAMP signaling in various types of cells, including β-cells, where it is involved in the control of insulin secretion. Upon activation, the protein redistributes to the plasma membrane but the underlying molecular mechanisms and functional consequences are unclear. Using quantitative high-resolution microscopy we found that cAMP elevation caused rapid binding of Epac2A to the β-cell plasma membrane, where it accumulated specifically at secretory granules and rendered them more prone to undergo exocytosis...
July 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28673934/activation-of-sf1-neurons-in-the-ventromedial-hypothalamus-by-dreadd-technology-increases-insulin-sensitivity-in-peripheral-tissues
#15
Eulalia A Coutinho, Shiki Okamoto, Ayako Wendy Ishikawa, Shigefumi Yokota, Nobuhiro Wada, Takahiro Hirabayashi, Kumiko Saito, Tatsuya Sato, Kazuyo Takagi, Chen-Chi Wang, Kenta Kobayashi, Yoshihiro Ogawa, Seiji Shioda, Yumiko Yoshimura, Yasuhiko Minokoshi
The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, whereas this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology...
July 3, 2017: Diabetes
https://www.readbyqxmd.com/read/28667119/mcl-1-is-a-key-anti-apoptotic-protein-in-human-and-rodent-pancreatic-%C3%AE-cells
#16
Kira Meyerovich, Natalia M Violato, Makiko Fukaya, Violette Dirix, Nathalie Pachera, Lorella Marselli, Piero Marchetti, Andreas Strasser, Decio L Eizirik, Alessandra K Cardozo
Induction of endoplasmic reticulum stress and activation of the intrinsic apoptotic pathway is widely believed to contribute to β-cell death in type 1 diabetes (T1D). MCL-1 is an anti-apoptotic member of the BCL-2 protein family, whose depletion causes apoptosis in rodent β-cells in vitro. Importantly, decreased MCL-1 expression was observed in islets from T1D patients. We report here that MCL-1 downregulation is associated with cytokine-mediated killing of human β-cells, a process partially prevented by MCL-1 overexpression...
June 30, 2017: Diabetes
https://www.readbyqxmd.com/read/28667118/the-gluco-and-liporegulatory-and-the-vasodilatory-effects-of-glucose-dependent-insulinotropic-polypeptide-gip-are-abolished-by-an-antagonist-of-the-human-gip-receptor
#17
Meena Asmar, Ali Asmar, Lene Simonsen, Lærke Smidt Gasbjerg, Alexander Hovard Sparre-Ulrich, Mette Rosenkilde, Bolette Hartmann, Flemming Dela, Jens Juul Holst, Jens Bülow
A truncated form of human GIP, GIP(3-30)NH2, was recently identified as an antagonist of the human GIP receptor. This study examined the ability of GIP(3-30)NH2 to antagonize the physiological actions of GIP in glucose metabolism, subcutaneous abdominal adipose tissue blood flow (ATBF) and lipid metabolism in humans.Eight lean subjects were studied by measuring arterio-venous concentrations of metabolites and ATBF on three different occasions during hyperglycemic-hyperinsulinemic clamps with concomitant infusions of either GIP, GIP(3-30)NH2 or both GIP and GIP(3-30)NH2During GIP(3-30)NH2 alone and in combination with GIP, insulin levels and the total glucose amount infused to maintain the clamp were lower than during GIP alone...
June 30, 2017: Diabetes
https://www.readbyqxmd.com/read/28663191/the-histone-methyltransferase-mll1-directs-macrophage-mediated-inflammation-in-wound-healing-and-is-altered-in-a-murine-model-of-obesity-and-type-2-diabetes
#18
Andrew Kimball, Amrita Joshi, William F Carson, Anna Boniakowski, Frank Davis, Matthew Schaller, Ronald Allen, Jennifer Bermick, Peter K Henke, Charles F Burant, Steve L Kunkel, Katherine A Gallagher
Macrophages are critical for the initiation and resolution of the inflammatory phase of wound repair. In diabetes, macrophages display a prolonged inflammatory phenotype in late wound healing. Recently, Mixed-Lineage Leukemia-1 (MLL1) has been shown to direct gene expression by regulating NFκB-mediated inflammatory gene transcription. Thus, we hypothesized that MLL1 influences macrophage-mediated inflammation in wound repair. We utilized a myeloid-specific Mll1 knockout(Mll1(f/f)Lyz2(Cre+) ) to determine the function of MLL1 in wound healing...
June 29, 2017: Diabetes
https://www.readbyqxmd.com/read/28663190/functional-and-structural-findings-of-neurodegeneration-in-early-stages-of-diabetic-retinopathy-cross-sectional-analyses-of-baseline-data-of-the-eurocondor-project
#19
Ana Rita Santos, Luísa Ribeiro, Francesco Bandello, Rosangela Lattanzio, Catherine Egan, Ulrik Frydkjaer-Olsen, José García-Arumí, Jonathan Gibson, Jakob Grauslund DMSci, Simon P Harding, Gabriele E Lang, Pascale Massin, Edoardo Midena, Peter Scanlon, Stephen J Aldington Hnd, Sílvia Simão, Christian Schwartz, Berta Ponsati, Massimo Porta, Miguel Ângelo Costa, Cristina Hernández, José Cunha-Vaz, Rafael Simó
Cross-sectional study evaluating the relationship between: a) functional and structural measurements of neurodegeneration in initial stages of diabetic retinopathy (DR); and b) presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of patients with type 2 diabetes (n=449) enrolled in the EUROCONDOR study (NCT01726075). Functional studies by multifocal ERG (mfERG) evaluated neurodysfunction and structural measurements using spectral domain optical-coherence tomography (SD-OCT) evaluated neurodegeneration...
June 29, 2017: Diabetes
https://www.readbyqxmd.com/read/28663189/erratum-national-institutes-of-health-sponsored-clinical-islet-transplantation-consortium-phase-3-trial-manufacture-of-a-complex-cellular-product-at-eight-processing-facilities-diabetes-2016-65-3418-3428
#20
Camillo Ricordi, Julia S Goldstein, A N Balamurugan, Gregory L Szot, Tatsuya Kin, Chengyang Liu, Christine W Czarniecki, Barbara Barbaro, Nancy D Bridges, Jose Cano, William R Clarke, Thomas L Eggerman, Lawrence G Hunsicker, Dixon B Kaufman, Aisha Khan, David-Erick Lafontant, Elina Linetsky, Xunrong Luo, James F Markmann, Ali Naji, Olle Korsgren, Jose Oberholzer, Nicole A Turgeon, Daniel Brandhorst, Andrew S Friberg, Ji Lei, Ling-Jia Wang, Joshua J Wilhelm, Jamie Willits, Xiaomin Zhang, Bernhard J Hering, Andrew M Posselt, Peter G Stock, A M James Shapiro
No abstract text is available yet for this article.
June 29, 2017: Diabetes
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