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Diabetes

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https://www.readbyqxmd.com/read/28811274/hypoxia-in-combination-with-muscle-contraction-improves-insulin-action-and-glucose-metabolism-in-human-skeletal-muscle-via-the-hif-1%C3%AE-pathway
#1
Sven W Görgens, Tim Benninghoff, Kristin Eckardt, Christian Springer, Alexandra Chadt, Anita Melior, Jakob Wefers, Andrea Cramer, Jørgen Jensen, Kåre I Birkeland, Christian A Drevon, Hadi Al-Hasani, Jürgen Eckel
Skeletal muscle insulin resistance is the hallmark of type 2 diabetes, and develops long before the onset of the disease. It is well accepted that physical activity improves glycemic control but the knowledge on underlying mechanisms mediating the beneficial effects remains incomplete. Exercise is accompanied by a decrease in intramuscular oxygen levels resulting in induction of HIF-1α. HIF-1α is a master regulator of gene expression and might play an important role in skeletal muscle function and metabolism...
August 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28801360/erratum-association-between-long-term-exposure-to-air-pollution-and-biomarkers-related-to-insulin-resistance-subclinical-inflammation-and-adipokines-diabetes-2016-65-3314-3326
#2
Kathrin Wolf, Anita Popp, Alexandra Schneider, Susanne Breitner, Regina Hampel, Wolfgang Rathmann, Christian Herder, Michael Roden, Wolfgang Koenig, Christa Meisinger, Annette Peters
No abstract text is available yet for this article.
August 11, 2017: Diabetes
https://www.readbyqxmd.com/read/28793985/long-term-hyperglycemia-naturally-induces-dental-caries-but-not-periodontal-disease-in-type-1-and-type-2-diabetic-rodents
#3
Yutaka Nakahara, Kiyokazu Ozaki, Tetsuro Matsuura
Periodontal disease (PD) in diabetic patients is described as the 6th complication of diabetes. We have previously shown that diabetes increases dental caries, and carious inflammation might have a strong effect on the adjacent periodontal tissue in diabetic rodent models. However, the possibility that hyperglycemia may induce PD in diabetic animals could not be completely eliminated. The goal of this study was to confirm the presence of PD in diabetic animal models by preventing carious inflammation with fluoride administration...
August 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28790135/ddb1-mediated-cry1-degradation-promotes-foxo1-driven-gluconeogenesis-in-liver
#4
Xin Tong, Deqiang Zhang, Nicholas Charney, Ethan Jin, Kyle Vandommelon, Kenneth Stamper, Neil Gupta, Johnny Saldate, Lei Yin
Targeted protein degradation through ubiquitination is an important step in the regulation of glucose metabolism. Here we present evidence that the DDB1-CUL4A ubiquitin E3 ligase functions as a novel metabolic regulator that promotes FOXO1-driven hepatic gluconeogenesis. In vivo, hepatocyte-specific Ddb1 deletion leads to impaired hepatic gluconeogenesis in the mouse liver but protects mice from high-fat diet (HFD)-induced hyperglycemia. Lack of Ddb1 downregulates FOXO1 protein expression and impairs FOXO1-driven gluconeogenic response...
August 8, 2017: Diabetes
https://www.readbyqxmd.com/read/28775125/smad3-stat3-signaling-mediates-%C3%AE-cell-epithelial-mesenchymal-transition-in-chronic-pancreatitis-related-diabetes
#5
Xiangwei Xiao, Shane Fischbach, Tina Zhang, Congde Chen, Qingfeng Sheng, Ray Zimmerman, Sneha Patnaik, Joseph Fusco, Yungching Ming, Ping Guo, Chiyo Shiota, Krishna Prasadan, Nupur Gangopadhyay, Sohail Z Husain, Henry Dong, George K Gittes
Many patients with chronic pancreatitis develop diabetes (chronic pancreatitis-related diabetes; CPRD) through an undetermined mechanism. Here, we used long-term partial pancreatic duct ligation (PDL) as a model to study CPRD. We found that long-term PDL induced significant β-cell dedifferentiation, followed by a time-dependent decrease in functional β-cell mass, all specifically in the ligated tail portion of the pancreas (PDL-tail). High levels of transforming growth factor β1 (TGFβ1) were detected in the PDL-tail, mainly produced by M2 macrophages at the early stage, and by activated myofibroblasts at the later stage...
August 3, 2017: Diabetes
https://www.readbyqxmd.com/read/28768703/opposite-regulation-of-insulin-sensitivity-by-dietary-lipid-versus-carbohydrate-excess
#6
Anne-Marie Lundsgaard, Kim A Sjøberg, Louise D Høeg, Jacob Jeppesen, Andreas B Jordy, Annette K Serup, Andreas M Fritzen, Henriette Pilegaard, Lene S Myrmel, Lise Madsen, Jørgen F P Wojtaszewski, Erik A Richter, Bente Kiens
To understand the mechanisms in lipid-induced insulin resistance, a more physiologic approach is to enhance FA availability through the diet. Nine healthy men ingested two hypercaloric diets (+75 E%) for three days, enriched in unsaturated FA (78 E% fat; UNSAT) or carbohydrates (80 E% carbohydrate; CHO) as well as a eucaloric control diet (CON). Compared to CON, UNSAT reduced whole body and leg glucose disposal during a hyperinsulinemic-euglycemic clamp, while decreasing hepatic glucose production. In muscle, DAG and IMTG were increased...
August 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28765322/structural-basis-and-genotype-phenotype-correlations-of-insr-mutations-causing-severe-insulin-resistance
#7
Jun Hosoe, Hiroko Kadowaki, Fuyuki Miya, Katsuya Aizu, Tomoyuki Kawamura, Ichiro Miyata, Kenichi Satomura, Takeru Ito, Kazuo Hara, Masaki Tanaka, Hiroyuki Ishiura, Shoji Tsuji, Ken Suzuki, Minaka Takakura, Keith A Boroevich, Tatsuhiko Tsunoda, Toshimasa Yamauchi, Nobuhiro Shojima, Takashi Kadowaki
The insulin receptor (INSR) gene was analyzed in four patients with severe insulin resistance, revealing 5 novel mutations and a deletion that removed exon 2. A patient with Donohue syndrome (DS) had a novel p.V657F mutation in the second fibronectin type III domain (FnIII-2), which contains the α-β cleavage site and part of the insulin-binding site. The mutant INSR was expressed in Chinese hamster ovary cells, revealing that it reduced insulin proreceptor processing and impaired activation of downstream signaling cascades...
August 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28765321/erratum-weight-loss-after-bariatric-surgery-reverses-insulin-induced-increases-in-brain-glucose-metabolism-of-the-morbidly-obese-diabetes-2013-62-2747-2751
#8
Jetro J Tuulari, Henry K Karlsson, Jussi Hirvonen, Jarna C Hannukainen, Marco Bucci, Mika Helmiö, Jari Ovaska, Minna Soinio, Paulina Salminen, Nina Savisto, Lauri Nummenmaa, Pirjo Nuutila
No abstract text is available yet for this article.
August 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28747378/nadph-oxidase-nox5-accelerates-renal-injury-in-diabetic-nephropathy
#9
Jay C Jha, Claudine Banal, Jun Okabe, Stephen P Gray, Thushan Hettige, Bryna S M Chow, Vicki Thallas-Bonke, Lisanne De Vos, Chet E Holterman, Melinda T Coughlan, David A Power, Alison Skene, Elif I Ekinci, Mark E Cooper, Rhian M Touyz, Chris R Kennedy, Karin Jandeleit-Dahm
NADPH-oxidase derived excessive production of reactive oxygen species (ROS) in the kidney plays a key role in mediating renal injury in diabetes. Pathological changes in diabetes include mesangial expansion and accumulation of extracellular matrix (ECM) leading to glomerulosclerosis. There is a paucity of data about the role of the Nox5 isoform of NADPH oxidase in animal models of diabetic nephropathy since Nox5 is absent in the mouse genome. Thus, we examined the role of Nox5 in human diabetic nephropathy, in human mesangial cells and in an inducible human Nox5 transgenic mouse exposed to STZ-induced diabetes...
July 26, 2017: Diabetes
https://www.readbyqxmd.com/read/28747377/erratum-loss-of-mbd2-protects-mice-against-high-fat-diet-induced-obesity-and-insulin-resistance-by-regulating-the-homeostasis-of-energy-storage-and-expenditure-diabetes-2016-65-3384-3395
#10
Jia Cheng, Jia Song, Xiaoyu He, Meng Zhang, Shuang Hu, Shu Zhang, Qilin Yu, Ping Yang, Fei Xiong, Dao Wen Wang, Jianfeng Zhou, Qin Ning, Zhishui Chen, Decio L Eizirik, Zhiguang Zhou, Chunxia Zhao, Cong-Yi Wang
No abstract text is available yet for this article.
July 26, 2017: Diabetes
https://www.readbyqxmd.com/read/28733313/granzyme-a-deficiency-breaks-immune-tolerance-and-promotes-autoimmune-diabetes-through-a-type-i-interferon-dependent-pathway
#11
Zia Ua Mollah, Hong Sheng Quah, Kate L Graham, Gaurang Jhala, Balasubramanian Krishnamurthy, Joanna Francisca M Dharma, Jonathan Chee, Prerak M Trivedi, Evan G Pappas, Leanne Mackin, Edward Pf Chu, Satoru Akazawa, Stacey Fynch, Charlotte Hodson, Andrew J Deans, Joseph A Trapani, Mark Mw Chong, Phillip I Bird, Thomas C Brodnicki, Helen E Thomas, Thomas Wh Kay
Granzyme A is a protease implicated in the degradation of intracellular DNA. Nucleotide complexes are known triggers of systemic autoimmunity, but a role in organ-specific autoimmune disease has not been demonstrated. To investigate whether such a mechanism could be an endogenous trigger for autoimmunity, we examined the impact of granzyme A deficiency in the NOD mouse model of autoimmune diabetes. Granzyme A deficiency resulted in an increased incidence in diabetes associated with accumulation of single stranded DNA in immune cells and induction of an interferon response in pancreatic islets...
July 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28729244/apoptosis-repressor-with-caspase-recruitment-domain-ameliorates-amyloid-induced-%C3%AE-cell-apoptosis-and-jnk-pathway-activation
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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