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Emilie Courty, Adrien Besseiche, Thi Thu Huong Do, Alexandrine Liboz, Fatima Mohamed Aguid, Evans Quilichini, Melissa Buscato, Pierre Gourdy, Jean-François Gautier, Jean-Pierre Riveline, Cécile Haumaitre, Marion Buyse, Bruno Fève, Ghislaine Guillemain, Bertrand Blondeau
Both type 1 and 2 diabetes are characterized by deficient insulin secretion and decreased beta-cell mass. Thus, regenerative strategies to increase beta-cell mass need to be developed. To characterize mechanisms of beta-cell plasticity, we studied a model of severe insulin resistance in the adult mouse and defined how beta cells adapt. Chronic corticosterone (CORT) treatment was given to adult mice and led to rapid insulin resistance and adaptive increased insulin secretion. Adaptive and massive increase of beta-cell mass was observed during treatment up to 8 weeks...
October 16, 2018: Diabetes
Janice J Hwang, Lihong Jiang, Elizabeth Sanchez Rangel, Xiaoning Fan, Yuyan Ding, Wai Lam, Jessica Leventhal, Feng Dai, Douglas L Rothman, Graeme F Mason, Robert S Sherwin
The impact of glycemic variability on brain glucose transport kinetics amongst T1DM individuals remains unclear. 14 individuals with T1DM (age 35±4 years, BMI 26.0±1.4 kg/m2 , HbA1C 7.6±0.3) and 9 healthy control participants (age 32±4, BMI 23.1±0.8, HbA1C 5.0±0.1) wore a continuous glucose monitor (Dexcom) to measure hypoglycemia, hyperglycemia and glycemic variability for 5 days followed by 1 H magnetic resonance spectroscopy scanning in the occipital lobe to measure the change in intracerebral glucose levels during a 2-hour glucose clamp (target glucose 220 mg/dl)...
October 16, 2018: Diabetes
David Endesfelder, Wolfgang Zu Castell, Ezio Bonifacio, Marian Rewers, William A Hagopian, Jin-Xiong She, Åke Lernmark, Jorma Toppari, Kendra Vehik, Alistair J K Williams, Liping Yu, Beena Akolkar, Jeffrey P Krischer, Anette-G Ziegler, Peter Achenbach
Progression to clinical type 1 diabetes varies between children developing beta-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles using a novel wavelet-based algorithm. We identified clusters of similar profiles, associated with different types of progression, among 600 children from The Environmental Determinants of Diabetes in the Young birth cohort study who developed persistent autoantibodies against insulin (IAA), GAD (GADA) and/or insulinoma-associated antigen-2 (IA-2A), and were followed prospectively in 3 to 6 months intervals (median follow-up 6...
October 10, 2018: Diabetes
Chloe Y Y Cheung, Chi-Ho Lee, Clara S Tang, Aimin Xu, Ka-Wing Au, Carol H Y Fong, Kelvin K K Ng, Kelvin H M Kwok, Wing-Sun Chow, Yu-Cho Woo, Michele Yuen, JoJo Hai, Kathryn C B Tan, Tai-Hing Lam, Hung-Fat Tse, Pak-Chung Sham, Karen S L Lam
Elevated circulating levels of pigment epithelium-derived factor (PEDF) have been reported in patients with type 2 diabetes (T2DM) and its associated microvascular complications. This study aimed to (i) identify the genetic determinants influencing circulating PEDF level in a clinical setting of T2DM; (ii) examine the relationship between circulating PEDF and diabetic complications; and (iii) explore the causal relationship between PEDF and diabetic complications. An exome-chip association study on circulating PEDF leve1 was conducted in 5385 Chinese subjects with T2DM...
October 10, 2018: Diabetes
Tatiana Danilova, Ilya Belevich, Huini Li, Erik Palm, Eija Jokitalo, Timo Otonkoski, Maria Lindahl
Global lack of mesencephalic astrocyte-derived neurotropic factor (MANF) leads to progressive postnatal loss of β-cells mass and insulin-dependent diabetes in mice. Similarly to Manf -/- mice, embryonic ablation of MANF specifically from the pancreas results in diabetes. In this study, we assessed the importance of MANF for the postnatal expansion of the pancreatic β-cell mass and for adult β-cell maintenance in mice. Detailed analysis of Pdx-1Cre +/- :: Manf fl/fl mice revealed mosaic MANF expression in postnatal pancreases and significant correlation between the number of MANF-positive β-cells and β-cell mass in individual mice...
October 10, 2018: Diabetes
Camille Allard, Jamie J Morford, Beibei Xu, Benjamin Salwen, Weiwei Xu, Lucie Desmoulins, Andrea Zsombok, Jason K Kim, Ellis R Levin, Franck Mauvais-Jarvis
Estrogens favor glucose homeostasis primarily through the estrogen receptor alpha (ERα), but the respective importance of nuclear and membrane ERα pools to glucose homeostasis are unknown. We studied glucose homeostasis, insulin secretion and insulin sensitivity in male and female mice expressing either the nuclear ERα (NOER) or the membrane ERα (MOER). Male and female MOER mice exhibited fasting and fed hyperglycemia and glucose intolerance. Female MOER mice displayed impaired central insulin signaling associated with hyperinsulinemia and insulin resistance due to unrestrained hepatic gluconeogenesis, without alterations in glucose stimulated-insulin secretion (GSIS)...
October 10, 2018: Diabetes
Brandon B Boland, Charles Brown, Michelle L Boland, Jennifer Cann, Michael Sulikowski, Gitte Hansen, Rikke V Grønlund, Wanda King, Cristina Rondinone, James Trevaskis, Christopher J Rhodes, Joseph S Grimsby
The onset of common obesity-linked type 2 diabetes (T2D) is marked by exhaustive failure of pancreatic β-cell functional mass to compensate for insulin resistance and increased metabolic demand, leading to uncontrolled hyperglycemia. Here, the β-cell deficient obese hyperglycemic/hyperinsulinemic KS db/db mouse model was used to assess consequential effects on β-cell functional recovery by lowering glucose homeostasis and/or improving insulin sensitivity following treatment with thiazolidinedione (TZD) therapy or glucagon-like-peptide-1 receptor (GLP-1R) agonism alone, or in combination with sodium/glucose cotransporter-2 inhibition (SGLT-2i)...
October 10, 2018: Diabetes
Eunjin Oh, Miwon Ahn, Solomon Afelik, Thomas C Becker, Bart O Roep, Debbie C Thurmond
Syntaxin 4 (Stx4) enrichment in human and mouse islet grafts improves transplant success in reversing STZ-induced diabetes in mice, although the underlying molecular mechanisms remain elusive. Toward further understanding this, human islets and inducible transgenic mice over-expressing Stx4 selectively in the islet β-cells (βTG-Stx4) were challenged with pro-inflammatory stressors in vitro and in vivo. Remarkably, βTG-Stx4 mice resisted multiple-low dose streptozotocin (STZ)-induced loss of β-cell mass and glucose intolerance; under standard conditions glucose tolerance was enhanced, maintaining normal fasting glycemia and insulinemia...
October 10, 2018: Diabetes
Ines De Mesmaeker, Thomas Robert, Krista G Suenens, Geert M Stangé, Freya Van Hulle, Zhidong Ling, Peter Tomme, Daniel Jacobs-Tulleneers-Thevissen, Bart Keymeulen, Daniel G Pipeleers
Alginate-encapsulated porcine islet cell grafts are developed to overcome limitations of human islet transplantation. They can generate functional implants in animals when prepared from fetal, perinatal and adult pancreases. Implants have not yet been examined for efficacy to establish sustained metabolically-adequate functional beta cell mass (FBM) with comparison to human islet cells. This study in immune-compromised mice demonstrates that subcutaneous implants of Alg-porcine-prenatal islet cells with 4x105 beta cells form, over 10 weeks, a FBM that results in glucose-induced plasma C-peptide >2 ng/mL and metabolic control over the following 10 weeks, with higher efficiency than non-encapsulated, while failing in peritoneum...
October 10, 2018: Diabetes
Claudia Menzaghi, Vincenzo Trischitta
No abstract text is available yet for this article.
October 10, 2018: Diabetes
Linyun He, Mowei Tang, Ting Xiao, Hailan Liu, Wei Liu, Guangdi Li, Feng Zhang, Yalun Xiao, Zhiguang Zhou, Feng Liu, Fang Hu
miRNAs are important regulators of differentiation, development and function of brown and beige fat cells. Here we identify the role of miR-199a/214 cluster in the regulation of brown and beige adipocyte development and thermogenesis in vitro and in vivo We show that expression of the miR-199a/214 cluster is dramatically decreased during brown and beige adipocyte differentiation and in response to cold exposure or β-adrenergic receptor activation. The cluster levels are significantly up-regulated in the adipose tissues of obese mice and human subjects...
October 2, 2018: Diabetes
Yuan-Yuan Xie, Chun-Li Mo, Yi-Huang Cai, Wen-Jie Wang, Xin-Xin Hong, Qing-Feng Liu, Yun-Jia Liu, Jing-Jing Hong, Ting He, Zhong-Zheng Zheng, Bo-An Li
Wnt/β-Catenin signaling plays a key role in regulating adipogenesis through indirectly inhibiting the expression of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ); however, the detailed molecular mechanism remains poorly understood. Moreover, the factor(s) that determines the Wnt/β-Catenin output level during adipogenesis is also not completely defined. In this study, we showed that Pygo2 exhibited a declined expression pattern during adipocyte differentiation, resulting in an attenuated Wnt/β-Catenin output level...
October 2, 2018: Diabetes
Mohammed A Alharbi, Citong Zhang, Chanyi Lu, Tatyana N Milovanova, Leah Yi, Je Dong Ryu, Hongli Jiao, Guangyu Dong, J Patrick O'Connor, Dana T Graves
Type 1 diabetes mellitus impairs fracture healing. We tested the hypothesis that diabetes affects chondrocytes to impair fracture healing through a mechanism that involves the transcription factor FOXO1. Type-1 diabetes was induced by streptozotocin in mice with FOXO1 deletion in chondrocytes (Col2α1Cre+ FOXO1L/L ) or littermate controls, (Col2α1Cre- FOXO1L/L ) and closed femoral fractures induced. Diabetic mice had 77% less cartilage and 30% less bone than normoglycemics evaluated histologically and by micro-CT...
October 2, 2018: Diabetes
Marie K Holt, James E Richards, Daniel R Cook, Daniel I Brierley, Diana L Williams, Frank Reimann, Fiona M Gribble, Stefan Trapp
Centrally administered glucagon-like peptide-1 (GLP-1) supresses food intake. Here we demonstrate that GLP-1-producing (PPG) neurons in the nucleus tractus solitarii (NTS) are the predominant source of endogenous GLP-1 within the brain. Selective ablation of NTS PPG neurons by viral expression of diphtheria toxin subunit A (DTA) substantially reduced active GLP-1 concentrations in brain and spinal cord. Contrary to expectations, this loss of central GLP-1 had no significant effect on ad libitum feeding of mice, affecting neither daily chow intake nor body weight or glucose tolerance...
October 2, 2018: Diabetes
Camille E Powe, Michael Nodzenski, Octavious Talbot, Catherine Allard, Catherine Briggs, Marysa V Leya, Patrice Perron, Luigi Bouchard, Jose C Florez, Denise M Scholtens, William L Lowe, Marie-France Hivert
Many common genetic polymorphisms are associated with glycemic traits and type 2 diabetes (T2D), but knowledge about genetic determinants of glycemic traits in pregnancy is limited. We tested genetic variants known to be associated with glycemic traits and T2D in the general population for associations with glycemic traits in pregnancy and gestational diabetes mellitus (GDM). Participants in two cohorts (Gen3G and HAPO) underwent oral glucose tolerance testing at 24-32 weeks gestation. We built genetic risk scores (GRSs) for elevated fasting glucose and insulin, reduced insulin secretion and sensitivity, and T2D, using variants discovered in studies of non-pregnant individuals; we tested for associations between these GRSs, glycemic traits in pregnancy, and GDM...
September 26, 2018: Diabetes
Weihua Tao, Yao Zhang, Lijuan Ma, Chujun Deng, Hualin Duan, Xuehua Liang, Rui Liao, Shaoqiang Lin, Tao Nie, Wanqun Chen, Cunchuan Wang, Carmenr Birchmeier, Shiqi Jia
Baseline beta-cell mass is established during the early postnatal period when beta cells expand. Here, we show that heterozygous ablation of Insm1 decreases baseline beta-cell mass and subsequently impairs glucose tolerance. When exposed to a high-fat diet or on an ob/ob background, glucose intolerance was more severe in Insm1 +/lacZ mice compared to Insm1 +/+ mice, although no further decrease in the beta-cell mass was detected. In islets of early postnatal Insm1 +/lacZ mice, cell cycle was prolonged in beta cells due to downregulation of the cell cycle gene Ccnd1 Although Insm1 had a low affinity for the Ccnd1 promoter compared to other binding sites, binding affinity was strongly dependent on Insm1 levels...
September 26, 2018: Diabetes
Chelsea L Faber, Miles E Matsen, Kevin R Velasco, Vincent Damian, Bao Anh Phan, Daniel Adam, Anthony Therattil, Michael W Schwartz, Gregory J Morton
The hypothalamic ventromedial nucleus (VMN) is implicated both in autonomic control of blood glucose and in behaviors including fear and aggression, but whether these divergent effects involve the same or distinct neuronal subsets and their projections is unknown. To address this question, we used an optogenetic approach to selectively activate the subset of VMN neurons that express neuronal nitric oxide synthase 1 (VMNNOS1 neurons) implicated in glucose counterregulation. We found that photo-activation of these neurons elicits 1) robust hyperglycemia achieved by activation of counterregulatory responses (CRRs) usually reserved for the physiological response to hypoglycemia, and 2) defensive immobility behavior...
September 26, 2018: Diabetes
Karyne L Vinales, Brittany Begaye, Clifton Bogardus, Mary Walter, Jonathan Krakoff, Paolo Piaggi
Fibroblast growth factor 21 (FGF21) regulates energy expenditure (EE) and influences weight change after low-protein overfeeding in rodent models. The change in EE after low-protein overfeeding diet is a predictor of weight change in humans and a feature of the "thrifty" metabolic phenotype. However, there are no studies showing an association between circulating FGF21 and EE in humans. We assessed the changes in plasma FGF21 concentrations after 24 hours of seven dietary interventions with different macronutrient content while in a whole-room indirect calorimeter in 64 healthy subjects with normal glucose regulation...
September 26, 2018: Diabetes
Kira Kuschnerus, Elisabeth T Straessler, Maja F Müller, Thomas F Lüscher, Ulf Landmesser, Nicolle Kränkel
Aggravated endothelial injury and impaired endothelial repair capacity contribute to the high cardiovascular risk in patients with type-2 diabetes (T2D), but the underlying mechanisms are still incompletely understood. Here we describe the functional role of miR-483-3p, which limits endothelial repair capacity in T2D patients. Expression of hsa-miR-483-3p was higher in endothelial-supportive M2-type macrophages (M2MΦ) and in the aortic wall of T2D patients than in non-diabetic controls. Likewise, mmu-miR-483* was higher in T2D than in nondiabetic murine carotid samples...
September 26, 2018: Diabetes
Young-Sun Lee, Changmi Lee, Jin-Seung Choung, Hye-Seung Jung, Hee-Sook Jun
Glucagon-like peptide-1 (GLP-1) can increase pancreatic β-cells, and α-cells could be a source for new β-cell generation. We investigated whether GLP-1 increases β-cells through α-cell transdifferentiation. New β-cells originating from non-β cells were significantly increased in recombinant adenovirus expressing GLP-1 (rAd-GLP-1)-treated RIP-CreER;R26-YFP mice. Proliferating α-cells were increased in islets of rAd-GLP-1-treated mice and αTC1-9 cells treated with exendin-4, a GLP-1 receptor agonist...
September 26, 2018: Diabetes
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