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Diabetes

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https://www.readbyqxmd.com/read/28213613/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-fat-mass-via-affecting-energy-expenditure
#1
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Shanghai Chen, Feifan Guo
Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet (HFD)-induced obesity, glucose intolerance and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or over-expression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein (bZIP) sites on its promoter...
February 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28209760/glucoraphanin-ameliorates-obesity-and-insulin-resistance-through-adipose-tissue-browning-and-reduction-of-metabolic-endotoxemia-in-mice
#2
Naoto Nagata, Liang Xu, Susumu Kohno, Yusuke Ushida, Yudai Aoki, Ryohei Umeda, Nobuo Fuke, Fen Zhuge, Yinhua Ni, Mayumi Nagashimada, Chiaki Takahashi, Hiroyuki Suganuma, Shuichi Kaneko, Tsuguhito Ota
Low-grade sustained inflammation links obesity to insulin resistance and nonalcoholic fatty liver disease (NAFLD). However, therapeutic approaches to improve systemic energy balance and chronic inflammation in obesity are limited. Pharmacological activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) alleviates obesity and insulin resistance in mice; however, Nrf2 inducers are not clinically available owing to safety concerns. Thus, we examined whether dietary glucoraphanin, a stable precursor of the Nrf2 inducer sulforaphane, ameliorates systemic energy balance, chronic inflammation, insulin resistance, and NAFLD in high-fat diet (HFD)-fed mice...
February 16, 2017: Diabetes
https://www.readbyqxmd.com/read/28202581/identification-and-functional-implications-of-sodium-myo-inositol-cotransporter-1-in-pancreatic-beta-cells-and-type-2-diabetes-mellitus
#3
Stephen Yu Ting Li, Sam Tsz Wai Cheng, Dan Zhang, Po Sing Leung
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28202580/spinal-disinhibition-in-experimental-and-clinical-painful-diabetic-neuropathy
#4
Andrew G Marshall, Corinne Lee-Kubli, Shazli Azmi, Michael Zhang, Maryam Ferdousi, Teresa Mixcoatl-Zecuatl, Ioannis N Petropoulos, Georgios Ponirakis, Mark S Fineman, Hassan Fadavi, Katie Frizzi, Mitra Tavakoli, Maria Jeziorska, Corinne G Jolivalt, Andrew J M Boulton, Nathan Efron, Nigel A Calcutt, Rayaz A Malik
Impaired rate dependent depression (RDD) of the Hoffman-reflex is associated with reduced dorsal spinal cord potassium chloride co-transporter expression and impaired spinal GABAA receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28193789/enriching-islet-phospholipids-with-eicosapentaenoic-acid-reduces-prostaglandin-e2-signaling-and-enhances-diabetic-%C3%AE-cell-function
#5
Joshua C Neuman, Michael D Schaid, Allison L Brill, Rachel J Fenske, Carly R Kibbe, Danielle A Fontaine, Sophia M Sdao, Harpreet K Brar, Kelsey M Connors, Haley N Wienkes, Kevin W Eliceiri, Matthew J Merrins, Dawn B Davis, Michelle E Kimple
Prostaglandin E2 (PGE2) is derived from arachidonic acid, while PGE3 is derived from eicosapentaenoic acid (EPA) using the same downstream metabolic enzymes. Little is known about the impact of EPA and PGE3 on β-cell function, particularly in the diabetic state. In this work, we determined PGE3 elicits a 10-fold weaker reduction in glucose-stimulated insulin secretion through the EP3 receptor as compared to PGE2 We tested the hypothesis that enriching pancreatic islet cell membranes with EPA, thereby reducing arachidonic acid abundance, would positively impact β-cell function in the diabetic state...
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28193788/erratum-metabolomic-profile-of-low-copy-number-carriers-at-the-salivary-%C3%AE-amylase-gene-suggests-a-metabolic-shift-toward-lipid-based-energy-production-diabetes-2016-65-3362-3368
#6
Abdelilah Arredouani, Matteo Stocchero, Nicola Culeddu, Julia El-Sayed Moustafa, Jean Tichet, Beverley Balkau, Thierry Brousseau, Marco Manca, Mario Falchi
No abstract text is available yet for this article.
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28193787/erratum-high-density-lipoproteins-rescue-diabetes-impaired-angiogenesis-via-scavenger-receptor-class-b-type-i-diabetes-2016-65-3091-3103
#7
Joanne T M Tan, Hamish C G Prosser, Louise L Dunn, Laura Z Vanags, Anisyah Ridiandries, Tania Tsatralis, Laura Leece, Zoë E Clayton, Sui Ching G Yuen, Stacy Robertson, Yuen Ting Lam, David S Celermajer, Martin K C Ng, Christina A Bursill
No abstract text is available yet for this article.
February 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28188143/statement-of-retraction-a-central-role-for-neuronal-amp-activated-protein-kinase-ampk-and-mammalian-target-of-rapamycin-mtor-in-high-protein-diet-induced-weight-loss-diabetes-2008-57-594-605-doi-10-2337-db07-0573
#8
Eduardo R Ropelle, José R Pauli, Maria Fernanda A Fernandes, Silvana A Rocco, Rodrigo M Marin, Joseane Morari, Kellen K Souza, Marília M Dias, Maria C Gomes-Marcondes, José A R Gontijo, Kleber G Franchini, Lício A Velloso, Mario J A Saad, José B C Carvalheira
No abstract text is available yet for this article.
February 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28188142/statement-of-retraction-tub-has-a-key-role-in-insulin-and-leptin-signaling-and-action-in-vivo-in-hypothalamic-nuclei-diabetes-2013-62-137-148-doi-10-2337-db11-1388
#9
Patrícia O Prada, Paula G F Quaresma, Andrea M Caricilli, Andressa C Santos, Dioze Guadagnini, Joseane Morari, Laís Weissmann, Eduardo R Ropelle, José Barreto C Carvalheira, Lício A Velloso, Mario J A Saad
No abstract text is available yet for this article.
February 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28188141/egfr-tyrosine-kinase-inhibitor-pd153035-improves-glucose-tolerance-and-insulin-action-in-high-fat-diet-fed-mice-diabetes-2009-58-2910-2919-doi-10-2337-db08-0506-pmid-19696185
#10
Patricia O Prada, Eduardo R Ropelle, Rosa H Mourão, Claudio T de Souza, Jose R Pauli, Dennys E Cintra, André Schenka, Silvana A Rocco, Roberto Rittner, Kleber G Franchini, José Vassallo, Lício A Velloso, José B Carvalheira, Mario J A Saad
No abstract text is available yet for this article.
February 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28174292/hypothalamic-and-striatal-insulin-action-suppresses-endogenous-glucose-production-and-may-stimulate-glucose-uptake-during-hyperinsulinemia-in-lean-but-not-in-overweight-men
#11
Martin Heni, Robert Wagner, Stephanie Kullmann, Sofiya Gancheva, Michael Roden, Andreas Peter, Norbert Stefan, Hubert Preissl, Hans Ulrich Häring, Andreas Fritsche
Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive.Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with D-[6,6-(2)H2]-glucose infusion to measure endogenous glucose production and glucose disappearance. On two days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an iv insulin bolus on placebo day...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28174291/local-sphingosine-kinase-1-activity-improves-islet-transplantation
#12
Darling Rojas-Canales, Daniella Penko, Kay K Myo Min, Kate A Parham, Heshan Peiris, Rainer V Haberberger, Stuart M Pitson, Chris Drogemuller, Damien J Keating, Shane T Grey, Patrick T Coates, Claudine S Bonder, Claire F Jessup
Pancreatic islet transplantation is a promising clinical treatment for type I diabetes (T1D), but success is limited by extensive beta cell death in the immediate post-transplant period, and impaired islet function in the longer term. Following transplantation, appropriate vascular remodelling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28174290/priming-effect-of-a-morning-meal-on-hepatic-glucose-disposition-later-in-the-day
#13
Mary Courtney Moore, Marta S Smith, Ben Farmer, Guillaume Kraft, Masakazu Shiota, Phillip E Williams, Alan D Cherrington
We used hepatic balance and tracer ((3)H-glucose) techniques to examine the impact of "breakfast" on hepatic glucose metabolism later in the same day. From 0-240 min, 2 groups (n=9 each) of conscious dogs received a duodenal infusion of glucose (GLC) or saline (SAL), then fasted from 240-360 min. Three dogs from each group were euthanized for tissue collection at 360 min. From 360-600 min, the remaining dogs underwent a hyperinsulinemic (4x basal) hyperglycemic clamp (arterial blood glucose 146±2 mg/dL) with portal glucose infusion...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28174289/vascular-effects-of-obestatin-in-lean-and-obese-subjects
#14
Francesca Schinzari, Augusto Veneziani, Nadia Mores, Angela Barini, Nicola Di Daniele, Carmine Cardillo, Manfredi Tesauro
Obese patients have impaired vasodilator reactivity and increased endothelin (ET)-1-mediated vasoconstriction, two abnormalities contributing to vascular dysfunction. Obestatin, a product of the ghrelin gene, in addition to favorable effects on glucose and lipid metabolism, has shown nitric oxide (NO)-dependent vasodilator properties in experimental models. Given these premises, we compared the effects of exogenous obestatin on forearm flow in lean and obese subjects and assessed its influence on ET-1-dependent vasoconstrictor tone in obesity...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28174288/direct-substrate-delivery-into-mitochondrial-fission-deficient-pancreatic-islets-rescues-insulin-secretion
#15
Uma D Kabra, Katrin Pfuhlmann, Adriana Migliorini, Susanne Keipert, Daniel Lamp, Olle Korsgren, Moritz Gegg, Stephen C Woods, Paul T Pfluger, Heiko Lickert, Charles Affourtit, Matthias H Tschöp, Martin Jastroch
In pancreatic beta cells, mitochondrial bioenergetics control glucose-stimulated insulin secretion (GSIS). Mitochondrial dynamics are generally associated with quality control, maintaining the functionality of bioenergetics. By acute pharmacological inhibition of mitochondrial fission protein Drp1, we here demonstrate that mitochondrial fission is necessary for GSIS in mouse and human islets. We confirm that genetic silencing of Drp1 increases mitochondrial proton leak in MIN6 cells. However, our comprehensive analysis of pancreatic islet bioenergetics reveals that Drp1 does not control insulin secretion via its effect on proton leak but instead via modulation of glucose-fuelled respiration...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28137793/increase-in-pancreatic-proinsulin-and-preservation-of-beta-cell-mass-in-autoantibody-positive-donors-prior-to-type-1-diabetes-onset
#16
Teresa Rodriguez-Calvo, Jose Zapardiel-Gonzalo, Natalie Amirian, Ericka Castillo, Yasaman Lajevardi, Lars Krogvold, Knut Dahl-Jørgensen, Matthias G von Herrath
Type 1 diabetes is characterized by the loss of insulin production due to beta cell dysfunction and/or destruction. The hypothesis that beta cell loss occurs early during the pre-diabetic phase has recently been challenged. Here we show, for the first time in situ that in pancreas sections from autoantibody positive donors (Ab+) insulin area and beta cell mass are maintained prior to disease onset, and that production of proinsulin increases. This suggests that beta cell destruction occurs more precipitously than previously assumed...
January 30, 2017: Diabetes
https://www.readbyqxmd.com/read/28137792/cardiac-autonomic-regulation-and-repolarization-during-acute-experimental-hypoglycemia-in-type-2-diabetes
#17
Elaine Chow, Alan Bernjak, Emma Walkinshaw, Alexandra Lubina-Solomon, Jenny Freeman, Ian A Macdonald, Paul J Sheridan, Simon R Heller
Hypoglycemia is associated with increased cardiovascular mortality in trials of intensive therapy in type 2 diabetes (T2DM). We previously observed an increase in arrhythmias during spontaneous prolonged hypoglycemia in T2DM patients. Our aim was to examine changes in cardiac autonomic function and repolarization during sustained experimental hypoglycemia.Twelve adults with T2DM and eleven age, BMI-matched nondiabetic controls underwent paired hyperinsulinemic clamps separated by 4 weeks. Glucose was maintained at euglycemia (6...
January 30, 2017: Diabetes
https://www.readbyqxmd.com/read/28137791/longitudinal-associations-between-ambient-air-pollution-with-insulin-sensitivity-%C3%AE-cell-function-and-adiposity-in-los-angeles-latino-children
#18
Tanya L Alderete, Rima Habre, Claudia M Toledo-Corral, Kiros Berhane, Zhanghua Chen, Frederick W Lurmann, Marc J Weigensberg, Michael I Goran, Frank D Gilliland
Evidence suggests that ambient air pollution (AAP) exposure may contribute to the development of obesity and type 2 diabetes. The objective of this study was to determine whether exposure to elevated concentrations of nitrogen dioxide (NO2) and particulate matter with aerodynamic diameter less than 2.5 (PM2.5) had adverse effects on longitudinal measures of insulin sensitivity, β-cell function, and obesity in children at high risk for developing diabetes. Overweight and obese Latino children (8-15 years; n=314) were enrolled between 2001-2012 from Los Angeles, California and followed for an average of 3...
January 30, 2017: Diabetes
https://www.readbyqxmd.com/read/28130310/reestablishment-of-glucose-inhibition-of-glucagon-secretion-in-small-pseudo-islets
#19
Christopher A Reissaus, David W Piston
Misregulated hormone secretion from the islet of Langerhans is central to the pathophysiology of diabetes. While insulin plays a key role in glucose regulation, the importance of glucagon is increasingly acknowledged. However, the mechanisms that regulate glucagon secretion from α-cells are still unclear. We utilized pseudo-islets reconstituted from dispersed islet cells to study α-cells with and without various indirect effects from other islet cells. Dispersed islet cells secrete aberrant levels of glucagon and insulin at basal and elevated glucose levels...
January 27, 2017: Diabetes
https://www.readbyqxmd.com/read/28130309/rare-loss-of-function-variants-in-npc1-predispose-to-human-obesity
#20
Ruixin Liu, Yaoyu Zou, Jie Hong, Min Cao, Bin Cui, Huiwen Zhang, Maopei Chen, Juan Shi, Tinglu Ning, Shaoqian Zhao, Wen Liu, Hui Xiong, Cuijie Wei, Zhengqing Qiu, Weiqiong Gu, Yifei Zhang, Wanyu Li, Lin Miao, Yingkai Sun, Minglan Yang, Rui Wang, Qinyun Ma, Min Xu, Yu Xu, Tiange Wang, Kei-Hang Katie Chan, Xianbo Zuo, Haoyan Chen, Lu Qi, Shenghan Lai, Shumin Duan, Baoliang Song, Yufang Bi, Simin Liu, Weiqing Wang, Guang Ning, Jiqiu Wang
Some evidence has indicated a role of NPC1 for obesity traits. However, whether the loss-of-function mutations in NPC1 cause adiposity in humans remains unknown. We recruited 25 probands with rare autosomal recessive Niemann-Pick type C (NP-C) disease and their parents in assessment of the effect of heterozygous NPC1 mutations on adiposity. We found that male NPC1(+/-) carriers had a significantly higher body mass index (BMI) than matched controls or the whole population-based controls. Consistently, male Npc1(+/-) mice had increased fat storage under high-fat diet...
January 27, 2017: Diabetes
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