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Active Brown Adipose Tissue is Associated With a Healthier Metabolic Phenotype in Obesity.

Carsten T Herz, Oana C Kulterer, Marlene Prager, Christoph Schmöltzer, Felix B Langer, Gerhard Prager, Rodrig Marculescu, Alexandra Kautzky-Willer, Marcus Hacker, Alexander R Haug, Florian W Kiefer,

Obesity is associated with increasing cardiometabolic morbidity and mortality worldwide. Not everyone with obesity, however, develops metabolic complications. Brown adipose tissue (BAT) has been suggested as a promoter of leanness and metabolic health. To date, little is known about the prevalence and metabolic function of BAT in subjects with severe ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Novel Human Insulin Isoforms and Cα-peptide Product in Islets of Langerhans and Choroid Plexus.

Qing-Rong Liu, Min Zhu, Pingbo Zhang, Caio H Mazucanti, Nicholas S Huang, Doyle L Lang, Qinghua Chen, Pavan Auluck, Stefano Marenco, Jennifer F O'Connell, Luigi Ferrucci, Chee W Chia, Josephine M Egan,

Human insulin (<i>INS</i>) gene diverged from the ancestral genes of invertebrate and mammalian species millions of years ago. We previously found that mouse insulin gene (<i>Ins2</i>) isoforms are expressed in brain choroid plexus (ChP) epithelium cells where insulin secretion is regulated by serotonin and not by glucose. We further compared ... Read more >>

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[2021, :]

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Relationship Between Insulin Secretion and Insulin Sensitivity and its Role in Development of Type 2 Diabetes Mellitus: Beyond the Disposition Index.

Elsa Vazquez Arreola, Robert L Hanson, Clifton Bogardus, William C Knowler,

We assessed whether the relationship between insulin secretion and sensitivity predicted development of type 2 diabetes in American Indians participating in a longitudinal epidemiologic study. At baseline, when all subjects did not have diabetes, 1566 participants underwent oral tests and 420 had intravenous measures of glucose regulation with estimates of ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Reduced Follicular Regulatory T Cells in Spleen and Pancreatic Lymph Nodes of Patients With Type 1 Diabetes.

Andrea Vecchione, Tatiana Jofra, Jolanda Gerosa, Kimberly Shankwitz, Roberta Di Fonte, Giuseppe Galvani, Elio Ippolito, Maria Pia Cicalese, Andrew R Schultz, Howie R Seay, Mariagrazia Favellato, Giulia Milardi, Angela Stabilini, Francesca Ragogna, Pauline Grogan, Eleonora Bianconi, Andrea Laurenzi, Amelia Caretto, Rita Nano, Raffaela Melzi, Nichole Danzl, Emanuele Bosi, Lorenzo Piemonti, Alessandro Aiuti, Todd Brusko, Constantinos Petrovas, Manuela Battaglia, Georgia Fousteri,

In the attempt to understand the origin of autoantibody (AAb) production in patients with and at-risk for T1D, multiple studies have analyzed and reported alterations in follicular helper T cells (Tfh) in presymptomatic AAb-positive subjects and patients with T1D. Yet, it is still not clear whether the regulatory counterpart of ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Possible Involvement of Adipose Tissue in Older and Obese Diabetic Patients with Coronavirus SARS-CoV-2 Infection (COVID-19) via GRP78 (BIP/HSPA5): Significance of Hyperinsulinemia Management in COVID-19.

Jihoon Shin, Shinichiro Toyoda, Shigeki Nishitani, Atsunori Fukuhara, Shunbun Kita, Michio Otsuki, Iichiro Shimomura,

Aging, obesity and diabetes are major risk factors for the severe progression and outcome of SARS-CoV-2 infection (COVID-19), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Increased Energy Expenditure and Protection from Diet-Induced Obesity in Mice Lacking the cGMP-Specific Phosphodiesterase PDE9.

Ryan P Ceddia, Dianxin Liu, Fubiao Shi, Mark K Crowder, Sumita Mishra, David A Kass, Sheila Collins,

Cyclic nucleotides, cAMP and cGMP, are important second messengers for the regulation of adaptive thermogenesis. Their levels are controlled not only by their synthesis but also their degradation. Since pharmacological inhibitors of cGMP-specific phosphodiesterase 9 (PDE9) can increase PKG signaling and UCP1 expression in adipocytes, we sought to elucidate the ... Read more >>

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[2021, :]

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Annexin 1 Mimetic Ac2-26 Holds Promise for the Treatment of Diabetic Nephropathy.

Yu Pan, Ming-Zhi Zhang, Raymond C Harris,

Diabetes (Diabetes)
[2021, 70(10):2183-2184]

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The Tetracycline-Controlled Transactivator (Tet-On/Off) System in Beta Cells Reduces Insulin Expression and Secretion in Mice.

Nathalie Jouvet, Khalil Bouyakdan, Scott A Campbell, Cindy Baldwin, Shannon E Townsend, Maureen A Gannon, Vincent Poitout, Thierry Alquier, Jennifer L Estall,

Controllable genetic manipulation is an indispensable tool in research, greatly advancing our understanding of cell biology and physiology. However in beta cells, transgene silencing, low inducibility, ectopic expression and off-targets effects are persistent challenges. In this study, we investigated whether an inducible, Tet-Off system with beta-cell specific MIP-itTA driven expression ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes.

Sharmaine Thirunavukarasu, Nicholas Jex, Amrit Chowdhary, Imtiaz Ul Hassan, Sam Straw, T P Craven Craven, M Gorecka, David Broadbent, Peter Swoboda, Klaus K Witte, Richard M Cubbon, Hui Xue, Peter Kellman, John P Greenwood, Sven Plein, Eylem Levelt,

Sodium-glucose-cotransporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalization for heart failure in type 2 diabetes (T2D) patients. Utilising cardiovascular magnetic resonance imaging (CMR) and 31phosphorus magnetic resonance spectroscopy(<sup>31</sup>P-MRS) in a longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2i empagliflozin on ... Read more >>

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[2021, :]

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Perirenal Fat and Chronic Kidney Disease in Patients With Diabetes.

Leonardo Roever, Gary Tse, Giuseppe Biondi-Zoccai,

Diabetes (Diabetes)
[2021, 70(10):2190-2191]

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Imeglimin ameliorates β-cell apoptosis by modulating the endoplasmic reticulum homeostasis pathway.

Jinghe Li, Ryota Inoue, Yu Togashi, Tomoko Okuyama, Aoi Satoh, Mayu Kyohara, Kuniyuki Nishiyama, Takahiro Tsuno, Daisuke Miyashita, Tatsuya Kin, A M James Shapiro, Resilind Su Ern Chew, Adrian Kee Keong Teo, Seiichi Oyadomari, Yasuo Terauchi, Jun Shirakawa,

The effects of imeglimin, a novel anti-diabetes agent, on β-cell function remain unclear. Here, we unveiled the impact of imeglimin on β-cell survival. Treatment with imeglimin augmented mitochondrial function, enhanced insulin secretion, promoted β-cell proliferation, and improved β-cell survival in mouse islets. Imeglimin upregulated the expression of endoplasmic reticulum (ER)-related ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Type 2 Diabetes, Glycemia, and Brain Health: The Complexity of Causality.

Velandai Srikanth,

Diabetes (Diabetes)
[2021, 70(10):2187-2189]

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What Regulates Basal Insulin Secretion and Causes Hyperinsulinemia?

Barbara E Corkey, Jude T Deeney, Matthew J Merrins,

We hypothesize that basal hyperinsulinemia is synergistically mediated by an interplay between increased oxidative stress and excess lipid in the form of reactive oxygen species (ROS) and long-chain acyl-CoA esters (LC-CoA). In addition, ROS production may increase in response to inflammatory cytokines and certain exogenous environmental toxins that mislead β-cells ... Read more >>

Diabetes (Diabetes)
[2021, 70(10):2174-2182]

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Found in Translation: Novel Insights Into Type 1 Diabetes and β-Cell Biology.

Holger A Russ, Howard W Davidson,

Diabetes (Diabetes)
[2021, 70(10):2185-2186]

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Probing β-Cell Biology in Space and Time.

Rafael Arrojo E Drigo,

β-Cells in the islet of Langerhans have a central role in maintaining energy homeostasis. Understanding the physiology of β-cells and other islet cells requires a deep understanding of their structural and functional organization, their interaction with vessels and nerves, the layout of paracrine interactions, and the relationship between subcellular compartments ... Read more >>

Diabetes (Diabetes)
[2021, 70(10):2163-2173]

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Diabetes and the Risk of Long-Term Post-COVID Symptoms.

César Fernández-de-Las-Peñas, Carlos Guijarro, Juan Torres-Macho, María Velasco-Arribas, Plaza-Canteli Susana, Valentín Hernández-Barrera, José A Arias-Navalón,

This study investigated the association of diabetes in patients who recovered from SARS-CoV-2 infection with the presence of long-term post-COVID symptoms. A case-control study including individuals hospitalised during the first wave of the pandemic was conducted. Patients with a previous diagnosis of diabetes and under medical control were considered cases. ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Contraction-Mediated Glucose Transport in Skeletal Muscle is Regulated by a Framework of AMPK, TBC1D1/4 and Rac1.

Christian de Wendt, Lena Espelage, Samaneh Eickelschulte, Christian Springer, Laura Toska, Anna Scheel, Awovi Didi Bedou, Tim Benninghoff, Sandra Cames, Torben Stermann, Alexandra Chadt, Hadi Al-Hasani,

The two closely related RabGTPase-activating proteins (RabGAPs) TBC1D1 and TBC1D4, both substrates for the AMP-activated protein kinase AMPK, play important roles in exercise metabolism and contraction-dependent translocation of the glucose transporter GLUT4 in skeletal muscle. However, the specific contribution of each RabGAP in contraction signaling is mostly unknown. In this ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study.

Jennifer E Nyland, Nazia T Raja-Khan, Kerstin Bettermann, Philippe A Haouzi, Douglas L Leslie, Jennifer L Kraschnewski, Leslie J Parent, Patricia Sue Grigson,

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of severe COVID-19 outcomes possibly due to dysregulated inflammatory responses. Glucose-regulating medications such as glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and pioglitazone are known to have anti-inflammatory effects that may improve outcomes in patients with SARS-CoV-2 ... Read more >>

Diabetes (Diabetes)
[2021, :]

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CD8+ T cells variably recognize native versus citrullinated GRP78 epitopes in type 1 diabetes.

Marie Eliane Azoury, Fatoumata Samassa, Mijke Buitinga, Laura Nigi, Noemi Brusco, Aïsha Callebaut, Matthieu Giraud, Magali Irla, Ana Ines Lalanne, Alexia Carré, Georgia Afonso, Zhicheng Zhou, Barbara Brandao, Maikel L Colli, Guido Sebastiani, Francesco Dotta, Maki Nakayama, Decio L Eizirik, Sylvaine You, Sheena Pinto, Mark J Mamula, Yann Verdier, Joelle Vinh, Soren Buus, Chantal Mathieu, Lut Overbergh, Roberto Mallone,

In type 1 diabetes, autoimmune β-cell destruction may be favored by neo-antigens harboring post-translational modifications such as citrullination. We studied the recognition of native and citrullinated glucose-regulated protein (GRP)78 peptides by CD8+ T cells. Citrullination modulated T-cell recognition and, to a lesser extent, HLA-A2 binding. GRP78-reactive CD8+ T cells circulated ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Gene Panel Sequencing of Patients With Monogenic Diabetes Brings to Light Genes Typically Associated With Syndromic Presentations.

Cécile Saint-Martin, Delphine Bouvet, Mathilda Bastide, Christine Bellanné Chantelot, ,

Gene panel sequencing (NGS) offers the possibility to analyze rare forms of monogenic diabetes (MgD). To that end, 18 genes were analyzed in 1676 patients referred for MODY genetic testing.Among the 307 patients with a molecular diagnosis of MgD, 55 (17.9%) were mutated in a gene associated with a genetic ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Syntaxin 4 enrichment in β-cells prevents conversion to autoimmune diabetes in non-obese diabetic (NOD) mice.

Eunjin Oh, Erika M McCown, Miwon Ahn, Pablo A Garcia, Sergio Branciamore, Shanshan Tang, De-Fu Zeng, Bart O Roep, Debbie C Thurmond,

Syntaxin 4 (STX4), a plasma membrane-localized SNARE protein, regulates human islet β-cell insulin secretion and preservation of β-cell mass. We found that human type 1 diabetic (T1D) and non-obese diabetic (NOD) mouse islets show reduced β-cell STX4 expression, consistent with decreased STX4 expression as a potential driver of T1D phenotypes. ... Read more >>

Diabetes (Diabetes)
[2021, :]

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The Deterrence of Rapid Metabolic Decline within 3 Months after Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes.

Emily K Sims, David Cuthbertson, Kevan C Herold, Jay M Sosenko,

Endpoints that provide an early identification of treatment effects are needed to implement type 1 diabetes prevention trials more efficiently. To this end, we assessed whether metabolic endpoints can be used to detect a teplizumab effect on rapid β-cell decline within 3 months after treatment in high-risk individuals in the ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Developmental Timing of High Fat Diet Exposure Impacts Glucose Homeostasis in Mice in a Sex-Specific Manner.

Maria M Glavas, Ann Y Lee, Ian Miao, Fan Yang, Mojibian Majid, Shannon M O'Dwyer, Timothy J Kieffer,

We previously demonstrated that male, but not female, Swiss Webster mice are susceptible to diabetes, with incidence increased by early overnutrition and high-fat diet (HFD). Here, we investigated how HFD in Swiss Webster males and females during preweaning, peripubertal, and post-pubertal periods alters glucose homeostasis and diabetes susceptibility. In males, ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Different effects of lifestyle intervention in high- and low-risk prediabetes.

Andreas Fritsche, Robert Wagner, Martin Heni, Kostantinos Kantartzis, Jürgen Machann, Fritz Schick, Rainer Lehmann, Andreas Peter, Corinna Dannecker, Louise Fritsche, Vera Valenta, Renate Schick, Peter Paul Nawroth, Stefan Kopf, Andreas Fh Pfeiffer, Stefan Kabisch, Ulrike Dambeck, Michael Stumvoll, Matthias Blüher, Andreas L Birkenfeld, Peter Schwarz, Hans Hauner, Julia Clavel, Jochen Seißler, Andreas Lechner, Karsten Müssig, Katharina Weber, Michael Laxy, Stefan Bornstein, Annette Schürmann, Michael Roden, Martin Hrabe de Angelis, Norbert Stefan, Hans-Ulrich Häring,

Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested if prediabetic individuals with low risk benefit from conventional LI and individuals with high risk benefit from an intensification of LI in a multi-center randomized controlled intervention over 12 months with ... Read more >>

Diabetes (Diabetes)
[2021, :]

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Activation of HIF1α Rescues the Hypoxic Response and Reverses Metabolic Dysfunction in the Diabetic Heart.

Maria da Luz Sousa Fialho, Ujang Purnama, Kaitlyn Mjh Dennis, Claudia N Montes Aparicio, Marcos Castro-Guarda, Emmanuelle Massourides, Damian J Tyler, Carolyn A Carr, Lisa C Heather,

Type 2 diabetes (T2D) impairs Hypoxia-Inducible Factor (HIF)1α activation, a master transcription factor that drives cellular adaptation to hypoxia. Reduced activation of HIF1α contributes to the impaired post-ischaemic remodelling observed following myocardial infarction in T2D. Molidustat is a HIF stabiliser currently undergoing clinical trials for the treatment of renal anaemia ... Read more >>

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[2021, :]

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