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Erratum. Hepatic CPT1A Facilitates Liver-Adipose Cross Talk via Induction of FGF21 in Mice. Diabetes 2022;71:31-42. Diabetes (IF 9.461) Pub Date : 2022-06-07 Wei Sun,Tao Nie,Kuai Li,Wenjie Wu,Qiaoyun Long,Tianshi Feng,Liufeng Mao,Yuan Gao,Qing Liu,Xuefei Gao,Dewei Ye,Kaixuan Yan,Ping Gu,Yong Xu,Xuemei Zhao,Kang Chen,Kerry Martin Loomes,Shaoqiang Lin,Donghai Wu,Xiaoyan Hui
In Fig. 3B of article cited above, for images of iWAT and eWAT, the labels "WT" and "LKO" were inadvertently transposed. LKO (Cpt1a knockout) should have been the label for the first set of images of adipose tissue, and WT (wild type) should have been the label for the second set of images. The authors apologize for the error. The online version of the article (https://doi.org/10.2337/db21-0363) has
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Diabetic Neuropathy in Hands: An Endemic Complication Waiting to Unfold? Diabetes (IF 9.461) Pub Date : 2022-05-27 Eva Sierra-Silvestre,Ricardo J Andrade,Andrea C Schroeter,Leanne Bisset,Michel W Coppieters
This cross-sectional study aimed to quantify the somatosensory dysfunction in the hand in people with diabetes with distal symmetrical polyneuropathy (DSPN) in hands; and explore early signs of nerve dysfunction in people with diabetes without DSPN in hands. The clinical diagnosis of DSPN was confirmed with electrodiagnosis and corneal confocal microscopy. Thermal and mechanical nerve function in the
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Antibody-Mediated Targeting of a Hybrid-Insulin-Peptide Towards Neonatal Thymic Langerin+ Cells Enhances T Cell Central Tolerance and Delays Autoimmune Diabetes. Diabetes (IF 9.461) Pub Date : 2022-05-27 Yong Lin,Jelena Perovanovic,Yuelin Kong,Botond Z Igyarto,Sandra Zurawski,Dean Tantin,Gerard Zurawski,Maria Bettini,Matthew L Bettini
Thymic presentation of self-antigens is critical for establishing a functional yet self-tolerant T cell population. Hybrid peptides formed through transpeptidation within pancreatic beta cell lysosomes have been proposed as a new class of autoantigens in Type 1 Diabetes (T1D). While the production of hybrid peptides in the thymus has not been explored, due to the nature of their generation, it is thought
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Causal Graph Between Serum Lipids and Glycemic Traits: a Mendelian Randomization Study. Diabetes (IF 9.461) Pub Date : 2022-05-27 Ziwei Zhu,Kai Wang,Xingjie Hao,Liangkai Chen,Zhonghua Liu,Chaolong Wang
We systematically investigated the bidirectional causality between high-densitylipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), triglycerides (TG), fasting insulin (FI), and glycated hemoglobin A1c (HbA1c) based on genome-wide association summary statistics of Europeans (sample size n = 1,320,016 for lipids, 151,013 for FI, and 344,182 for HbA1c). We applied multivariable
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Targeting Pancreatic Islet NLRP3 Improves Islet Graft Revascularization. Diabetes (IF 9.461) Pub Date : 2022-05-27 Selina Wrublewsky,Thimoteus Speer,Lisa Nalbach,Anne S Boewe,Mandy Pack,Dalia Alansary,Leticia P Roma,Markus D A Hoffmann,Beate M Schmitt,Andrea Weinzierl,Michael D Menger,Matthias W Laschke,Emmanuel Ampofo
Hypoxia-induced islet cell death, caused by an insufficient revascularization of the grafts, is a major obstacle for successful pancreatic islet transplantation. Recently, it has been reported that the nucleotide-binding oligomerization domain (NOD)-like receptor protein (NLRP)3 inflammasome is expressed in pancreatic islets and its loss protects against hypoxia-induced cell death. Therefore, we hypothesized
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Infant Mesenchymal Stem Cell Insulin Action is Associated With Maternal Plasma Free Fatty Acids, Independent of Obesity Status: The Healthy Start Study. Diabetes (IF 9.461) Pub Date : 2022-05-27 Alec B Chaves,Donghai Zheng,Jonathan A Johnson,Bryan C Bergman,Zachary W Patinkin,Vincent Zaegel,Ericka M Biagioni,Polina Krassovskaia,Nicholas T Broskey,Linda E May,Dana Dabelea,Joseph A Houmard,Kristen E Boyle
Preclinical rodent and non-human primate models investigating maternal obesity have highlighted the importance of the intrauterine environment for development of insulin resistance in the offspring; however, it remains unclear if these findings can be translated to humans. To investigate possible intrauterine effects in humans, we isolated mesenchymal stem cells (MSCs) from the umbilical cord tissue
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The Effect of Glucagon on Protein Catabolism During Insulin Deficiency - Exchange of Amino acids Across Skeletal Muscle and The Splanchnic Bed. Diabetes (IF 9.461) Pub Date : 2022-05-27 Haleigh James,Wilson I Gonsalves,Shankarappa Manjunatha,Surendra Dasari,Ian R Lanza,Katherine A Klaus,Adrian Vella,James C Andrews,K Sreekumaran Nair
Transient insulin deprivation with concurrent hyperglucagonemia is a catabolic state that can occur in type 1 diabetes. To evaluate glucagon's catabolic effect in the setting of its glucogenic effect, we measured the regional exchanges of amino-metabolites across muscle and splanchnic beds in 16 healthy humans during either somatostatin followed by glucagon or a saline infusion alone. Despite a ≥2-fold
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The p66Shc Protein Mediates Insulin Resistance and Secretory Dysfunction in Pancreatic Beta-Cells Under Lipotoxic Conditions. Diabetes (IF 9.461) Pub Date : 2022-05-25 Giuseppina Biondi,Nicola Marrano,Lucia Dipaola,Anna Borrelli,Martina Rella,Rossella D'Oria,Valentina A Genchi,Cristina Caccioppoli,Immacolata Porreca,Angelo Cignarelli,Sebastio Perrini,Piero Marchetti,Leonardo Vincenti,Luigi Laviola,Francesco Giorgino,Annalisa Natalicchio
We evaluated the role of the p66Shc redox adaptor protein in pancreatic beta-cell insulin resistance that develops under lipotoxic conditions and with excess body fat. Prolonged exposure to palmitate in vitro or the presence of overweight/obesity augmented p66Shc expression levels and caused an impaired ability of exogenous insulin to increase cellular insulin content and secreted C-peptide levels
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New Evidence of Central Nervous System Damage in Diabetes Mellitus: Impairment of Fine Visual Discrimination. Diabetes (IF 9.461) Pub Date : 2022-05-25 He Chen,Menghan Wang,Lin Xia,Jiong Dong,Guangwei Xu,Ziyi Wang,Lixia Feng,Yifeng Zhou
Diabetes can damage both the peripheral sensory organs, causing retinopathy, as well as the central visual system, leading to contrast sensitivity and impaired color vision in patients without retinopathy. Orientation discrimination is important for shape recognition by the visual system. Our psychophysical findings in this study show diminished orientation discrimination in diabetic patients without
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T-Cell Autoreactivity in Type 2 Diabetes: Benign or Pathogenic, Smoke or Fire? Diabetes (IF 9.461) Pub Date : 2022-06-01 Angus G Jones,Martin Eichmann
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Roflumilast-Mediated Phosphodiesterase 4D Inhibition Reverses Diabetes-Associated Cardiac Dysfunction and Remodeling: Effects Beyond Glucose Lowering. Diabetes (IF 9.461) Pub Date : 2022-05-20 Rui Xu,Jing Fu,Yuting Hu,Xiaoyan Yang,Xiang Tao,Long Chen,Kai Huang,Qin Fu
Patients with type 2 diabetes have a substantial risk of developing cardiovascular disease. Phosphodiesterase 4 (PDE4) dysregulation is of pathophysiological importance in metabolic disorders. To determine the role of PDE4 in diabetic cardiac dysfunction, mice fed with high-fat diet (HFD) were treated by pharmacological inhibition of PDE4 or cardiac specific knocking down of PDE4D. Mice on HFD developed
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Vertical Sleeve Gastrectomy Lowers SGLT2/Slc5a2 Expression in the Mouse Kidney. Diabetes (IF 9.461) Pub Date : 2022-05-20 Elina Akalestou,Livia Lopez-Noriega,Iain R Tough,Ming Hu,Isabelle Leclerc,Helen M Cox,Guy A Rutter
Bariatric surgery improves glucose homeostasis but the underlying mechanisms are not fully elucidated. Here, we show that the expression of sodium glucose cotransporter-2 (SGLT2/Slc5a2) is reduced in the kidney of lean and obese mice following vertical sleeve gastrectomy (VSG). Indicating an important contribution of altered cotransporter expression to the impact of surgery, inactivation of the SGLT2/Slc5a2
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The Transcription Factor YY1 is Essential for Normal DNA Repair and Cell Cycle in Human and Mouse β-cells. Diabetes (IF 9.461) Pub Date : 2022-05-20 Flavia Letícia Martins Peçanha,Rami Jaafar,Joao Pedro Werneck-de-Castro,Charalampia-Christina Apostolopolou,Anil Bhushan,Ernesto Bernal-Mizrachi
Identifying the mechanisms behind the β-cell adaptation-to-failure is important to develop strategies to manage type 2 diabetes (T2D). Using db/db mice at early stages of the disease process, we took advantage of unbiased RNAseq to identify genes/pathways regulated by insulin resistance in β-cells. We demonstrate herein that islets from 4-week-old non-obese and non-diabetic leptin-receptor deficient
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Pericyte Control of Blood Flow in Intraocular Islet Grafts Impacts Glucose Homeostasis in Mice. Diabetes (IF 9.461) Pub Date : 2022-05-19 Alejandro Tamayo,Luciana Gonçalves,Rayner Rodriguez-Diaz,Elizabeth Pereira,Melissa Canales,Alejandro Caicedo,Joana Almaça
The pancreatic islet depends on blood supply to efficiently sense plasma glucose levels and deliver insulin and glucagon into the circulation. Long thought to be passive conduits of nutrients and hormones, islet capillaries were recently found to be densely covered with contractile pericytes with the capacity to locally control blood flow. Here we determined the contribution of pericyte regulation
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Plasma ApoM levels and Progression to Kidney Dysfunction in Type 1 Diabetics. Diabetes (IF 9.461) Pub Date : 2022-05-12 Nathaniel L Baker,Samar M Hammad,Kelly J Hunt,Andrea Semler,Richard L Klein,Maria F Lopes-Virella
Apolipoprotein M (apoM), which is mainly carried by HDL, has been associated with several conditions including cardiovascular disease and diabetic nephropathy. This study proposes to examine whether plasma apoM levels are associated with the development of diabetic kidney disease, assessed as progression to macroalbuminuira and chronic kidney disease. Plasma apoM was measured using an enzyme immunoassay
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Immunogenicity and safety of SARS-CoV-2 mRNA vaccines in a cohort of patients with type 1 diabetes. Diabetes (IF 9.461) Pub Date : 2022-05-12 Francesca D'Addio,Gianmarco Sabiu,Vera Usuelli,Emma Assi,Ahmed Abdelsalam,Anna Maestroni,Andy Joe Seelam,Moufida Ben Nasr,Cristian Loretelli,Davide Mileto,Giada Rossi,Ida Pastore,Laura Montefusco,Paola S Morpurgo,Laura Plebani,Antonio Rossi,Enrica Chebat,Andrea M Bolla,Elena Lunati,Chiara Mameli,Maddalena Macedoni,Spinello Antinori,Stefano Rusconi,Maurizio Gallieni,Cesare Berra,Franco Folli,Massimo
Patients with type 1 diabetes (T1D) may develop severe outcomes during COVID-19 disease, but their ability to generate an immune response against the SARS-CoV-2 messenger RNA (mRNA) vaccines remains to be established. Here we evaluated the safety, immunogenicity and glycometabolic effects of the SARS-CoV-2 mRNA vaccines in patients with T1D. A total of 375 patients, 326 with T1D and 49 non-diabetics
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Predictive Metabolomic Markers in Early to Mid-Pregnancy for Gestational Diabetes: A Prospective Test and Validation Study. Diabetes (IF 9.461) Pub Date : 2022-05-09 Yeyi Zhu,Dinesh K Barupal,Amanda L Ngo,Charles P Quesenberry,Juanran Feng,Oliver Fiehn,Assiamira Ferrara
Gestational diabetes (GDM) predisposes pregnant individuals to perinatal complications and long-term diabetes and cardiovascular diseases. We developed and validated metabolomic markers for GDM in a prospective test-validation study. In a case-control sample within the PETALS cohort (91 GDM, 180 non-GDM; discovery set), a random PETALS subsample (42 GDM, 372 non-GDM; validation set 1), and a case-control
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Endothelial Prohibitin Mediates Bi-directional Long Chain Fatty Acid Transport in White and Brown Adipose Tissues. Diabetes (IF 9.461) Pub Date : 2022-05-02 Zhanguo Gao,Alexes C Daquinag,Yongmei Yu,Mikhail G Kolonin
The function of Prohibitin-1 (PHB1) in adipocyte mitochondrial respiration, adaptive thermogenesis, and long chain fatty acid (LCFA) metabolism has been reported. While intracellular PHB1 expression is ubiquitous, cell surface PHB1 localization is selective for adipocytes and endothelial cells of adipose tissue. The importance of PHB1 in adipose endothelium has not been investigated and its vascular
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Circulating C-Peptide Levels in Living Children and Young People and Pancreatic Beta Cell Loss in Pancreas Donors Across Type 1 Diabetes Disease Duration. Diabetes (IF 9.461) Pub Date : 2022-05-02 Alice L J Carr,Jamie R J Inshaw,Christine S Flaxman,Pia Leete,Rebecca C Wyatt,Lydia A Russell,Matthew Palmer,Dmytro Prasolov,Thomas Worthington,Bethany Hull,Linda S Wicker,David B Dunger,Richard A Oram,Noel G Morgan,John A Todd,Sarah J Richardson,Rachel E J Besser
C-peptide declines in type 1 diabetes although many long-duration patients retain low, but detectable levels. Histological analyses confirm that beta cells can remain following type 1 diabetes onset. We explored the trends observed in C-peptide decline in UK Genetic Resource Investigating Diabetes (UK GRID) cohort (N=4,079), with beta cell loss in pancreas donors from the network for Pancreatic Organ
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Identification of Novel Disease-Relevant Genes and Pathways in the Pathogenesis of Type 1 Diabetes: A Potential Defect in Pancreatic Iron Homeostasis. Diabetes (IF 9.461) Pub Date : 2022-05-02 Linda Yip,Reem Alkhataybeh,Cariel Taylor,Rebecca Fuhlbrigge,C Garrison Fathman
Multiple pathways contribute to the pathophysiological development of type 1 diabetes (T1D), however, the exact mechanisms involved are unclear. We performed differential gene expression analysis in pancreatic islets of non-obese diabetic (NOD) mice versus age-matched congenic NOD.B10 controls to identify genes that may contribute to disease pathogenesis. Novel genes related to extracellular matrix
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Indirect and Direct Effects of SARS-CoV-2 on Human Pancreatic Islets. Diabetes (IF 9.461) Pub Date : 2022-05-02 Moufida Ben Nasr,Francesca D'Addio,Laura Montefusco,Vera Usuelli,Cristian Loretelli,Antonio Rossi,Ida Pastore,Ahmed Abdelsalam,Anna Maestroni,Marco Dell'Acqua,Elio Ippolito,Emma Assi,Andy Joe Seelam,Roberta Maria Fiorina,Enrica Chebat,Paola Morpurgo,Maria Elena Lunati,Andrea Mario Bolla,Reza Abdi,Joseph V Bonventre,Stefano Rusconi,Agostino Riva,Domenico Corradi,Pierachille Santus,Pamela Clark,Manuela
Recent studies have shown that SARS-CoV-2 infection may induce metabolic distress, leading to hyperglycemia in patients affected by COVID-19. We investigated the potential indirect and direct effects of SARS-CoV-2 on human pancreatic islets in 10 patients who became hyperglycemic after COVID-19. While there was no evidence of peripheral anti-islet autoimmunity, the serum of these patients displayed
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Differentiating Associations of Glycemic Traits with Atherosclerotic and Thrombotic Outcomes: Mendelian Randomization Investigation. Diabetes (IF 9.461) Pub Date : 2022-05-02 Shuai Yuan,Amy M Mason,Stephen Burgess,Susanna C Larsson
We conducted a Mendelian randomization analysis to differentiate associations of four glycemic indicators with a broad range of atherosclerotic and thrombotic diseases. Independent genetic variants associated with fasting glucose (FG), 2-h glucose after an oral glucose challenge (2hGlu), fasting insulin (FI), and glycated hemoglobin (HbA1c) at the genome-wide significance threshold were used as instrumental
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GIPR Agonism Inhibits PYY-Induced Nausea-Like Behavior. Diabetes (IF 9.461) Pub Date : 2022-05-02 Ricardo J Samms,Richard Cosgrove,Brandy M Snider,Ellen C Furber,Brian A Droz,Daniel A Briere,James Dunbar,Mridula Dogra,Jorge Alsina-Fernandez,Tito Borner,Bart C De Jonghe,Matthew R Hayes,Tamer Coskun,Kyle W Sloop,Paul J Emmerson,Minrong Ai
The induction of nausea and emesis is a major barrier to maximizing the weight loss profile of obesity medications, and therefore, identifying mechanisms that improve tolerability could result in added therapeutic benefit. The development of Peptide YY (PYY)-based approaches to treat obesity are no exception, as PYY receptor agonism is often accompanied by nausea and vomiting. Here, we sought to determine
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Glucose-Dependent miR-125b is a Negative Regulator of β-Cell Function Diabetes (IF 9.461) Pub Date : 2022-04-27 Rebecca Cheung,Grazia Pizza,Pauline Chabosseau,Delphine Rolando,Alejandra Tomas,Thomas Burgoyne,Zhiyi Wu,Anna Salowka,Anusha Tapa,Annabel Macklin,Yufei Cao,Marie-Sophie Nguyen-Tu,Matthew T. Dickerson,David A. Jacobson,Piero Marchetti,James Shapiro,Lorenzo Piemonti,Eelco de Koning,Isabelle Leclerc,Karim Bouzakri,Kei Sakamoto,David M. Smith,Guy A. Rutter,Aida Martinez-Sanchez
Impaired pancreatic β-cell function and insulin secretion are hallmarks of type 2 diabetes. MicroRNAs are short non-coding RNAs that silence gene expression, vital for the development and function of β-cells. We have previously shown that β-cell specific deletion of the important energy sensor AMP-activated protein kinase (AMPK) results in increased miR-125b-5p levels. Nevertheless, the function of
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GLP-2 Regulation of Dietary Fat Absorption and Intestinal Chylomicron Production via Neuronal Nitric Oxide Synthase (nNOS) Signaling. Diabetes (IF 9.461) Pub Date : 2022-04-27 Elisabeth M Grande,Fitore Raka,Simon Hoffman,Khosrow Adeli
Postprandial dyslipidemia is a metabolic condition commonly associated with insulin-resistant states, such as obesity and type 2 diabetes (T2D). It is characterized by the overproduction of intestinal chylomicron particles and excess atherogenic chylomicron remnants in circulation. We have previously shown that glucagon-like peptide-2 (GLP-2) augments dietary fat uptake and chylomicron production in
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Botulinum Injection into the Proximal Intestinal Wall of Diet-induced Obese Mice Leads to Weight Loss and Improves Glucose and Fat Tolerance. Diabetes (IF 9.461) Pub Date : 2022-04-27 Sinju Sundaresan,Joseph Antoun,Babak Banan,Jamie Adcock,Connor Johnson,Brendan Claire,Kala Dixon,Joyce Flynn,Cyndya A Shibao,Naji Abumrad
Botulinum neurotoxin (available commercially as BOTOX®) has been used successfully for treatment of several neuromuscular disorders including blepharospasm, dystonia, spasticity, and cerebral palsy in children. Our data demonstrate that injection of BOTOX® into the proximal intestinal wall of diet-induced obese (DIO) mice induces weight loss and reduces food intake. This was associated with amelioration
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Hepatic GSK3β-dependent CRY1 Degradation Contributes to Diabetic Hyperglycemia. Diabetes (IF 9.461) Pub Date : 2022-04-27 Ye Young Kim,Hagoon Jang,Gung Lee,Yong Geun Jeon,Jee Hyung Sohn,Ji Seul Han,Won Taek Lee,Jeu Park,Jin Young Huh,Hahn Nahmgoong,Sang Mun Han,Jeesoo Kim,Minwoo Pak,Sun Kim,Jong-Seo Kim,Jae Bum Kim
Excessive hepatic glucose production (HGP) is a key factor promoting hyperglycemia in diabetes. Hepatic cryptochrome 1 (CRY1) plays an important role in maintaining glucose homeostasis by suppressing forkhead box protein O1 (FOXO1)-mediated HGP. Although downregulation of hepatic CRY1 appears to be associated with increased HGP, the mechanism(s) by which hepatic CRY1 dysregulation confers hyperglycemia
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Mitofusins Mfn1 and Mfn2 are Required to Preserve Glucose- But Not Incretin-Stimulated Beta Cell Connectivity and Insulin Secretion Diabetes (IF 9.461) Pub Date : 2022-04-26 Eleni Georgiadou,Charanya Muralidharan,Michelle Martinez,Pauline Chabosseau,Elina Akalestou,Alejandra Tomas,Fiona Yong Su Wern,Theodoros Stylianides,Asger Wretlind,Cristina Legido-Quigley,Ben Jones,Livia Lopez Noriega,Yanwen Xu,Guoqiang Gu,Nour Alsabeeh,Céline Cruciani-Guglielmacci,Christophe Magnan,Mark Ibberson,Isabelle Leclerc,Yusuf Ali,Scott A. Soleimanpour,Amelia K. Linnemann,Tristan A. Rodriguez
Mitochondrial glucose metabolism is essential for stimulated insulin release from pancreatic beta cells. Whether mitofusin gene expression, and hence mitochondrial network integrity, is important for glucose or incretin signalling has not previously been explored. Here, we generated mice with beta cell-selective, adult-restricted deletion of the mitofusin genes Mfn1 and Mfn2 (βMfn1/2 dKO). βMfn1/2
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LncRNA-H19 in Fibroblasts Promotes Diabetic Wound Healing. Diabetes (IF 9.461) Pub Date : 2022-04-26 Pijun Yu,Jian Guo,Junjie Li,Xiao Shi,Ning Xu,Yongkang Jiang,Wei Chen,Qin Hu
Cutaneous wound healing in diabetes is impaired and would develop into nonhealing ulcerations. However, the molecular mechanism underlying the wound-healing process remains largely obscure. Here, we found that cutaneous PDGFRα+ fibroblast-expressing lncRNA-H19 (lncH19) accelerates the wound-healing process via promoting dermal fibroblast proliferation and macrophage infiltration in injured skin. PDGFRα+
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β-Cell Succinate Dehydrogenase Deficiency Triggers Metabolic Dysfunction and Insulinopenic Diabetes. Diabetes (IF 9.461) Pub Date : 2022-04-26 Sooyeon Lee,Haixia Xu,Aidan Van Vleck,Alex M Mawla,Albert Mao Li,Jiangbin Ye,Mark O Huising,Justin P Annes
Mitochondrial dysfunction plays a central role in Type 2 Diabetes (T2D); however, the pathogenic mechanisms in pancreatic β-cells are incompletely elucidated. Succinate dehydrogenase (SDH) is a key mitochondrial enzyme with dual functions in the TCA cycle and electron transport chain (ETC). Using human diabetic samples and a mouse model of β-cell-specific SDH ablation (SDHBβKO), we define SDH deficiency
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HIF-2α Preserves Mitochondrial Activity And Glucose Sensing in Compensating Beta Cells in Obesity. Diabetes (IF 9.461) Pub Date : 2022-04-26 Jae-Su Moon,Matthew Riopel,Jong Bae Seo,Vicente Herrero-Aguayo,Roi Isaac,Yun Sok Lee
In obesity, increased mitochondrial metabolism with the accumulation of oxidative stress leads to mitochondrial damage and beta cell dysfunction. In particular, beta cells express anti-oxidant enzymes at relatively low levels and are highly vulnerable to oxidative stress. Early in the development of obesity, beta cells exhibit increased GSIS, in order to compensate for insulin resistance. This increase
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Endogenous Lipid-GPR120 Signaling Modulates Pancreatic Islet Homeostasis to Different Extents. Diabetes (IF 9.461) Pub Date : 2022-04-26 Ya-Qin Du,Xue-Ying Sha,Jie Cheng,Jin Wang,Jing-Yu Lin,Wen-Tao An,Wei Pan,Li-Jun Zhang,Xiao-Na Tao,YunFei Xu,Ying-Li Jia,Zhao Yang,Peng Xiao,Ming Liu,Jin-Peng Sun,Xiao Yu
Long-chain fatty acids (LCFAs) not only are energy sources but also serve as signaling molecules. GPR120, an LCFA receptor, plays key roles in maintaining metabolic homeostasis. However, whether endogenous ligand-GPR120 circuits exist and how such circuits function in pancreatic islets are unclear. Here, we found that endogenous GPR120 activity in pancreatic δ cells modulated islet functions. At least
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DOC2b Enhances β-Cell Function via a Novel Tyrosine Phosphorylation-Dependent Mechanism. Diabetes (IF 9.461) Pub Date : 2022-06-01 Diti Chatterjee Bhowmick,Arianne Aslamy,Supriyo Bhattacharya,Eunjin Oh,Miwon Ahn,Debbie C Thurmond
Double C2 domain Β (DOC2b) protein is required for glucose-stimulated insulin secretion (GSIS) in β-cells, the underlying mechanism of which remains unresolved. Our biochemical analysis using primary human islets and human and rodent clonal β-cells revealed that DOC2b is tyrosine phosphorylated within 2 min of glucose stimulation, and Src family kinase member YES is required for this process. Biochemical
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Leptin Signaling Suppression in Macrophages Improves Immunometabolic Outcomes in Obesity Diabetes (IF 9.461) Pub Date : 2022-04-04 Lauar de Brito Monteiro,Juliana Silveira Prodonoff,Cristhiane Favero de Aguiar,Felipe Correa-da-Silva,Angela Castoldi,Nikki van Teijlingen Bakker,Gustavo Gastão Davanzo,Bianca Castelucci,Jéssica Aparecida da Silva Pereira,Jonathan Curtis,Jörg Büscher,Larissa Menezes Dos Reis,Gisele Castro,Guilherme Ribeiro,João Victor Virgílio-da-Silva,Douglas Adamoski,Sandra Martha Gomes Dias,Silvio Roberto Consonni
Obesity is a major concern for global healthcare systems. Systemic low-grade inflammation in obesity is a major risk factor for insulin resistance. Leptin is an adipokine secreted by the adipose tissue that functions by controlling food intake, leading to satiety. Leptin levels are increased in obesity. Here, we show that leptin enhances the effects of LPS in macrophages, intensifying the production
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Circulating Metabolites Associate With and Improve the Prediction of All-Cause Mortality in Type 2 Diabetes. Diabetes (IF 9.461) Pub Date : 2022-06-01 Maria Giovanna Scarale,Mario Mastroianno,Cornelia Prehn,Massimiliano Copetti,Lucia Salvemini,Jerzy Adamski,Salvatore De Cosmo,Vincenzo Trischitta,Claudia Menzaghi
Death rate is increased in type 2 diabetes. Unraveling biomarkers of novel pathogenic pathways capable to identify high-risk patients is instrumental to tackle this burden. We investigated the association between serum metabolites and all-cause mortality in type 2 diabetes and then whether the associated metabolites mediate the effect of inflammation on mortality risk and improve ENFORCE (EstimatioN
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p38α Deficiency in T Cells Ameliorates Diet-Induced Obesity, Insulin Resistance, and Adipose Tissue Senescence. Diabetes (IF 9.461) Pub Date : 2022-06-01 Deyun Meng,Baohua Zhang,Yanyan Wang,Tingting Zheng,Ran Hu,Bin Wang,Kinya Otsu,Ying Wang,Gonghua Huang
Adipose tissue-resident T cells play vital roles in regulating inflammation and metabolism in obesity, but the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding enhances p38 activity in adipose-resident T cells. T cell-specific deletion of p38α, an essential subunit of p38 expressed in most immune cells, protected mice from HFD-induced obesity, hepatic steatosis,
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Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes (IF 9.461) Pub Date : 2022-04-01 Emily K Sims,Rachel E J Besser,Colin Dayan,Cristy Geno Rasmussen,Carla Greenbaum,Kurt J Griffin,William Hagopian,Mikael Knip,Anna E Long,Frank Martin,Chantal Mathieu,Marian Rewers,Andrea K Steck,John M Wentworth,Stephen S Rich,Olga Kordonouri,Anette-Gabriele Ziegler,Kevan C Herold,
Most screening programs to identify individuals at risk for type 1 diabetes have targeted relatives of people living with the disease to improve yield and feasibility. However, ∼90% of those who develop type 1 diabetes do not have a family history. Recent successes in disease-modifying therapies to impact the course of early-stage disease have ignited the consideration of the need for and feasibility
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When Adipose Tissue Lets You Down: Understanding the Functions of Genes Disrupted in Lipodystrophy. Diabetes (IF 9.461) Pub Date : 2022-04-01 Justin J Rochford
Lipodystrophy syndromes are conditions in which the adipose tissue mass of an individual is altered inappropriately. The change in adipose mass can range from a relatively modest and subtle redistribution in some individuals with partial lipodystrophy to a near-complete absence of adipose tissue in the most severe forms of generalized lipodystrophy. The common feature is a disconnection between the
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Response to Comment on Espinosa De Ycaza et al. Adipose Tissue Inflammation Is Not Related to Adipose Insulin Resistance in Humans. Diabetes 2022;71:381-393. Diabetes (IF 9.461) Pub Date : 2022-04-01 Ana Elena Espinosa De Ycaza,Esben Søndergaard,Michael D Jensen
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Comment On Espinosa De Ycaza et al. Adipose Tissue Inflammation Is Not Related to Adipose Insulin Resistance in Humans. Diabetes 2022;71:381-393. Diabetes (IF 9.461) Pub Date : 2022-04-01 Inez Trouwborst,Gijs H Goossens
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Keeping It Local in Metabolic Disease: Adipose Tissue Paracrine Signaling and Insulin Resistance. Diabetes (IF 9.461) Pub Date : 2022-04-01 Darcy E Kahn,Bryan C Bergman
Alterations in adipose tissue composition and function are associated with obesity and contribute to the development of type 2 diabetes. While the significance of this relationship has been cemented, our understanding of the multifaceted role of adipose tissue in metabolic heath and disease continues to evolve and expand. Heterogenous populations of cells that make up adipose tissue throughout the
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Genome-Wide Association Study Identifies Genetic Loci Associated With Fat Cell Number and Overlap With Genetic Risk Loci for Type 2 Diabetes. Diabetes (IF 9.461) Pub Date : 2022-06-01 Agné Kulyté,Alisha Aman,Rona J Strawbridge,Peter Arner,Ingrid A Dahlman
Interindividual differences in generation of new fat cells determine body fat and type 2 diabetes risk. In the GENetics of Adipocyte Lipolysis (GENiAL) cohort, which consists of participants who have undergone abdominal adipose biopsy, we performed a genome-wide association study (GWAS) of fat cell number (n = 896). Candidate genes from the genetic study were knocked down by siRNA in human adipose-derived
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A Special Thanks to the Reviewers of Diabetes Diabetes (IF 9.461) Pub Date : 2022-03-22 David A. D’Alessio
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Genetic Reduction of Glucose Metabolism Preserves Functional β-Cell Mass in KATP-Induced Neonatal Diabetes. Diabetes (IF 9.461) Pub Date : 2022-06-01 Zihan Yan,Manuela Fortunato,Zeenat A Shyr,Amy L Clark,Matt Fuess,Colin G Nichols,Maria S Remedi
β-Cell failure and loss of β-cell mass are key events in diabetes progression. Although insulin hypersecretion in early stages has been implicated in β-cell exhaustion/failure, loss of β-cell mass still occurs in KATP gain-of-function (GOF) mouse models of human neonatal diabetes in the absence of insulin secretion. Thus, we hypothesize that hyperglycemia-induced increased β-cell metabolism is responsible
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Serum Metabolomics of Incident Diabetes and Glycemic Changes in a Population With High Diabetes Burden: The Hispanic Community Health Study/Study of Latinos. Diabetes (IF 9.461) Pub Date : 2022-06-01 Jin Choul Chai,Guo-Chong Chen,Bing Yu,Jiaqian Xing,Jun Li,Tasneem Khambaty,Krista M Perreira,Marisa J Perera,Denise C Vidot,Sheila F Castaneda,Elizabeth Selvin,Casey M Rebholz,Martha L Daviglus,Jianwen Cai,Linda Van Horn,Carmen R Isasi,Qi Sun,Meredith Hawkins,Xiaonan Xue,Eric Boerwinkle,Robert C Kaplan,Qibin Qi
Metabolomic signatures of incident diabetes remain largely unclear for the U.S. Hispanic/Latino population, a group with high diabetes burden. We evaluated the associations of 624 known serum metabolites (measured by a global, untargeted approach) with incident diabetes in a subsample (n = 2,010) of the Hispanic Community Health Study/Study of Latinos without diabetes and cardiovascular disease at
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Impaired Cold-Stimulated Supraclavicular Brown Adipose Tissue Activity in Young Boys With Obesity. Diabetes (IF 9.461) Pub Date : 2022-06-01 Basma A Ahmed,Nina Varah,Frank J Ong,Denis P Blondin,Elizabeth Gunn,Norman B Konyer,Nina P Singh,Michael D Noseworthy,Francois Haman,Andre C Carpentier,Zubin Punthakee,Gregory R Steinberg,Katherine M Morrison
Childhood obesity is a growing worldwide problem. In adults, lower cold-induced brown adipose tissue (BAT) activity is linked to obesity and metabolic dysfunction; this relationship remains uncertain in children. In this cross-sectional study, we compared cold-induced supraclavicular (SCV) BAT activity (percent change in proton density fat fraction [PDFF]) within the SCV region after 1 h of whole-body
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Incidence of an Insulin-Requiring Hyperglycemic Syndrome in SARS CoV-2-Infected Young Individuals: Is it Type 1 Diabetes? Diabetes (IF 9.461) Pub Date : 2022-03-16 Massimo Pietropaolo,Peter Hotez,Nick Giannoukakis
Pancreatic Angiotensin Converting Enzyme 2 receptor (ACE2) expression, together with increased prevalence of insulin-requiring hyperglycemia in COVID-19 patients, suggested that SARS CoV-2 pancreatic infection might trigger a beta cell-selective inflammation precipitating autoimmune type 1 diabetes (T1D). We examined T1D incidence in COVID-19 patients inside a large, global population using a "big
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Maternal Exercise-Induced SOD3 Reverses the Deleterious Effects of Maternal High-Fat Diet on Offspring Metabolism Through Stabilization of H3K4me3 and Protection Against WDR82 Carbonylation. Diabetes (IF 9.461) Pub Date : 2022-06-01 Joji Kusuyama,Nathan S Makarewicz,Brent G Albertson,Ana Barbara Alves-Wagner,Royce H Conlin,Noah B Prince,Christiano R R Alves,Krithika Ramachandran,Chisayo Kozuka,Yang Xiudong,Yang Xia,Michael F Hirshman,Toshihisa Hatta,Ryoichi Nagatomi,Eva S Nozik,Laurie J Goodyear
Preclinical studies reveal maternal exercise as a promising intervention to reduce the transmission of multigenerational metabolic dysfunction caused by maternal obesity. The benefits of maternal exercise on offspring health may arise from multiple factors and have recently been shown to involve DNA demethylation of critical hepatic genes leading to enhanced glucose metabolism in offspring. Histone
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Blood Neuroexosomal Mitochondrial Proteins Predict Alzheimer Disease in Diabetes. Diabetes (IF 9.461) Pub Date : 2022-06-01 Haiyan Chi,Ran Yao,Chao Sun,Bing Leng,Tengqun Shen,Tong Wang,Shukun Zhang,Mengfan Li,Yachao Yang,Hairong Sun,Zhenguang Li,Jinbiao Zhang
There is accumulating evidence that mitochondrial dysfunction is associated with the contribution of diabetes to Alzheimer disease (AD) progression. Neuronal mitochondrial proteins are found in plasma neuronal-derived exosomes (NDEs) at levels that reflect those in brain neurons. Here, we tested the performance of mitochondrial proteins in plasma NDEs to predict cognitive decline and brain injury in
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Very-Long-Chain Unsaturated Sphingolipids Mediate Oleate-Induced Rat β-Cell Proliferation Diabetes (IF 9.461) Pub Date : 2022-03-14 Anne-Laure Castell,Alexis Vivoli,Trevor S. Tippetts,Isabelle Robillard Frayne,Zuraya Elisa Angeles,Valentine S. Moullé,Scott A. Campbell,Matthieu Ruiz,Julien Ghislain,Christine Des Rosiers,William L. Holland,Scott A. Summers,Vincent Poitout
Fatty acid (FA) signaling contributes to β-cell mass expansion in response to nutrient excess, but the underlying mechanisms are poorly understood. In the presence of elevated glucose, FA metabolism is shifted toward synthesis of complex lipids, including sphingolipids. Here, we tested the hypothesis that sphingolipids are involved in the β-cell proliferative response to FA. Isolated rat islets were
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The Role of Long Noncoding RNA MALAT1 in Diabetic Polyneuropathy and the Impact of Its Silencing in the Dorsal Root Ganglion by a DNA/RNA Heteroduplex Oligonucleotide. Diabetes (IF 9.461) Pub Date : 2022-06-01 Akiko Miyashita,Masaki Kobayashi,Satoru Ishibashi,Tetsuya Nagata,Ambika Chandrasekhar,Douglas W Zochodne,Takanori Yokota
Diabetic polyneuropathy (DPN) is the most common complication of diabetes, yet its pathophysiology has not been established. Accumulating evidence suggests that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays pivotal roles in the regulation of cell growth and survival during diabetic complications. This study aimed to investigate the impact of MALAT1 silencing
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Independent of Renox, NOX5 Promotes Renal Inflammation and Fibrosis in Diabetes by Activating ROS-Sensitive Pathways. Diabetes (IF 9.461) Pub Date : 2022-06-01 Jay C Jha,Aozhi Dai,Jessica Garzarella,Amelia Charlton,Sofia Urner,Jakob A Østergaard,Jun Okabe,Chet E Holterman,Alison Skene,David A Power,Elif I Ekinci,Melinda T Coughlan,Harald H H W Schmidt,Mark E Cooper,Rhian M Touyz,Chris R Kennedy,Karin Jandeleit-Dahm
Excessive production of renal reactive oxygen species (ROS) plays a major role in diabetic kidney disease (DKD). Here, we provide key findings demonstrating the predominant pathological role of the pro-oxidant enzyme NADPH oxidase 5 (NOX5) in DKD, independent of the previously characterized NOX4 pathway. In patients with diabetes, we found increased expression of renal NOX5 in association with enhanced
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Erratum. The Women’s Leadership Gap in Diabetes: A Call for Equity and Excellence. Diabetes 2021;70:1623–1633 Diabetes (IF 9.461) Pub Date : 2022-03-05 Jessica L. Dunne,Jennifer L. Maizel,Amanda L. Posgai,Mark A. Atkinson,Linda A. DiMeglio
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Connecting Genomics and Proteomics to Identify Protein Biomarkers for Adult and Youth-Onset Type 2 Diabetes: A Two-Sample Mendelian Randomization Study. Diabetes (IF 9.461) Pub Date : 2022-06-01 Faegheh Ghanbari,Nahid Yazdanpanah,Mojgan Yazdanpanah,J Brent Richards,Despoina Manousaki
Type 2 diabetes shows an increasing prevalence in both adults and children. Identification of biomarkers for both youth and adult-onset type 2 diabetes is crucial for development of screening tools or drug targets. In this study, using two-sample Mendelian randomization (MR), we identified 22 circulating proteins causally linked to adult type 2 diabetes and 11 proteins with suggestive evidence for
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Fat Distribution Within the Pancreas According to Diabetes Status and Insulin Traits. Diabetes (IF 9.461) Pub Date : 2022-06-01 Loren Skudder-Hill,Ivana R Sequeira,Jaelim Cho,Juyeon Ko,Sally D Poppitt,Maxim S Petrov
A growing body of evidence suggests that intrapancreatic fat is associated with diabetes, but whether distribution of intrapancreatic fat across the regions of the pancreas has a pathophysiologic role is unknown. The aim of this study was to investigate the differences in intrapancreatic fat deposition between the head, body, and tail of the pancreas, as well as the relationship between regional intrapancreatic
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Rate-Dependent Depression: A Predictor of the Therapeutic Efficacy in Treating Painful Diabetic Peripheral Neuropathy. Diabetes (IF 9.461) Pub Date : 2022-06-01 Xiajun Zhou,Ying Zhu,Ze Wang,Zhi Lin,Desheng Zhu,Chong Xie,Nigel A Calcutt,Yangtai Guan
We investigated the application of rate-dependent depression (RDD) of the Hoffmann (H) wave as a predictor of treatment efficacy in patients with painful diabetic peripheral neuropathy (DPN). General medical information, scales, and nerve conduction data were collected from 73 healthy subjects, 50 subjects with type 2 diabetes and painless DPN, and 71 subjects with type 2 diabetes and painful DPN.
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ATP-Sensitive Potassium Channels in Hyperinsulinism and Type 2 Diabetes: Inconvenient Paradox or New Paradigm? Diabetes (IF 9.461) Pub Date : 2022-03-01 Colin G Nichols,Nathaniel W York,Maria S Remedi
Secretion of insulin from pancreatic β-cells is complex, but physiological glucose-dependent secretion is dominated by electrical activity, in turn controlled by ATP-sensitive potassium (KATP) channel activity. Accordingly, loss-of-function mutations of the KATP channel Kir6.2 (KCNJ11) or SUR1 (ABCC8) subunit increase electrical excitability and secretion, resulting in congenital hyperinsulinism (CHI)
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The Need to Increase Clinical Skills and Change the Genetic Testing Strategy for Monogenic Diabetes. Diabetes (IF 9.461) Pub Date : 2022-03-01 Rosa Di Paola,Antonella Marucci,Vincenzo Trischitta
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Comment on De Wendt et al. Contraction-Mediated Glucose Transport in Skeletal Muscle Is Regulated by a Framework of AMPK, TBC1D1/4, and Rac1. Diabetes 2021;70:2796-2809. Diabetes (IF 9.461) Pub Date : 2022-03-01 Rasmus Kjøbsted,Jørgen F P Wojtaszewski
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Imeglimin to the Rescue: Enhanced CHOP/GADD34/eIF2α Signaling Axis Promotes β-Cell Survival. Diabetes (IF 9.461) Pub Date : 2022-03-01 Seokwon Jo,Emilyn U Alejandro