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Bruno Halpern, Marcio C Mancini, Clarissa Bueno, Isabella P Barcelos, Maria Edna de Melo, Marcos S Lima, Camila G Carneiro, Marcelo T Sapienza, Carlos Alberto Buchpiguel, Fernanda Gaspar do Amaral, José Cipolla-Neto
Melatonin, a pineal hormone synthesized at night, is critical for the synchronization of circadian and seasonal rhythms, being a key regulator of energy metabolism in many animal species. Although studies in humans are lacking, several reports, mainly on hibernating animals, demonstrate that melatonin supplementation and short photoperiod increase brown adipose tissue (BAT) mass. The present proof-of-concept study is the first, to our knowledge, to evaluate BAT in melatonin non-proficient patients (radiotherapy or surgical removal of pineal gland) before and after daily melatonin (3 mg) replacement for three months...
February 14, 2019: Diabetes
Jun Yuan, Joanne Tm Tan, Kushwin Rajamani, Emma L Solly, Emily J King, Laura Lecce, Philippa Jl Simpson, Yuen Ting Lam, Alicia J Jenkins, Christina A Bursill, Anthony C Keech, Martin Kc Ng
Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, reduces lower limb amputations in patients with type 2 diabetes mellitus. The mechanism is, however, unknown. Here we demonstrate that fenofibrate markedly attenuates diabetes-related impairment of ischemia-mediated angiogenesis. In a murine model of hindlimb ischemia, daily oral fenofibrate treatment restored diabetes-impaired blood flow recovery, foot movement, hindlimb capillary density, vessel diameter, and vascular endothelial growth factor (VEGF) signaling to non-diabetic levels in both wildtype and PPARα-knockout mice, indicating that these fenofibrate effects are largely PPARα-independent...
February 14, 2019: Diabetes
Trevor P Fidler, Alex Marti, Katelyn Gerth, Elizabeth A Middleton, Robert A Campbell, Matthew T Rondina, Andrew S Weyrich, E Dale Abel
Patients with type 1 diabetes mellitus (T1DM) have increased thrombosis and platelet activation. The mechanisms for platelet hyperactivation in diabetes are incompletely understood. T1DM is accompanied by hyperglycemia, dyslipidemia, and increased inflammation, in addition to an altered hormonal milieu. In vitro analysis of platelets revealed that normal glucose reduces platelet activation while hyperglycemic conditions increase platelet activation. We therefore hypothesized that hyperglycemia increases platelet glucose utilization, which increases platelet activation to promote thrombosis...
February 14, 2019: Diabetes
Yurika Katsu-Jiménez, Carmela Vázquez-Calvo, Camilla Maffezzini, Maria Halldin, Xiaoxiao Peng, Christoph Freyer, Anna Wredenberg, Alfredo Giménez-Cassina, Anna Wedell, Elias S J Arnér
Thioredoxin Interacting Protein (TXNIP) is an alpha arrestin that can bind to and inhibit the antioxidant protein thioredoxin (TXN). TXNIP expression is induced by glucose, promotes ß-cell apoptosis in the pancreas and deletion of its gene in mouse models protects against diabetes. TXNIP is currently studied as a potential new target for antidiabetic drug therapy. Here we describe a family with a mutation in the TXNIP gene leading to non-detectable expression of TXNIP protein. Symptoms of affected family members include lactic acidosis and low serum methionine levels...
February 12, 2019: Diabetes
Martin G Myers
No abstract text is available yet for this article.
February 11, 2019: Diabetes
Geoffrey P Roberts, Pierre Larraufie, Paul Richards, Richard G Kay, Sam G Galvin, Emily L Miedzybrodzka, Andrew Leiter, H Joyce Li, Leslie L Glass, Marcella K L Ma, Brian Lam, Giles S H Yeo, Raphaël Scharfmann, Davide Chiarugi, Richard H Hardwick, Frank Reimann, Fiona M Gribble
Enteroendocrine cells (EECs) produce hormones such as glucagon-like peptide 1 and peptide YY that regulate food absorption, insulin secretion, and appetite. Based on the success of glucagon-like peptide 1-based therapies for type 2 diabetes and obesity, EECs are themselves the focus of drug discovery programs to enhance gut hormone secretion. The aim of this study was to identify the transcriptome and peptidome of human EECs and to provide a cross-species comparison between humans and mice. By RNA sequencing of human EECs purified by flow cytometry after cell fixation and staining, we present a first transcriptomic analysis of human EEC populations and demonstrate a strong correlation with murine counterparts...
February 7, 2019: Diabetes
Menaka C Thounaojam, Annalisa Montemari, Folami L Powell, Prerana Malla, Diana R Gutsaeva, Alessandra Bachettoni, Guido Ripandelli, Andrea Repossi, Amany Tawfik, Pamela M Martin, Francesco Facchiano, Manuela Bartoli
We have investigated the contributing role of monosodium urate (MSU) to the pathological processes associated with the induction of diabetic retinopathy (DR). In human postmortem retinas and vitreous from donors with DR, we have found a significant increase in MSU levels which correlated with the presence of inflammatory markers and enhanced expression of xanthine oxidase. Same elevation in MSU levels was also detected in serum and vitreous of streptozotocin-induced diabetic rats (STZ-rats) analyzed at 8 weeks of hyperglycemia...
February 6, 2019: Diabetes
Claudia Kruger, Trang-Tiffany Nguyen, Chelsea Breaux, Alana Guillory, Margaret Mangelli, Kevin T Fridianto, Jean-Paul Kovalik, David H Burk, Robert C Noland, Randall Mynatt, Krisztian Stadler
Proximal tubular epithelial cells are highly energy demanding. Their energy need is covered mostly from mitochondrial fatty acid oxidation. It is suggested, but not entirely clear whether derailments in fatty acid metabolism and mitochondrial dysfunction are forerunners of tubular damage. Here we modeled mitochondrial overload by creating mice lacking the enzyme carnitine acetyl-transferase (CrAT) in the proximal tubules, thus limiting a primary mechanism to export carbons under conditions of substrate excess...
February 6, 2019: Diabetes
Ho Seon Park, Hak Zoo Kim, Jong Suk Park, Junyeop Lee, Seung-Pyo Lee, Hail Kim, Chul Woo Ahn, Yoshikazu Nakaoka, Gou Young Koh, Shinae Kang
Islets are highly vascularized for prompt insulin secretion. Although angiopoietin-1 (Ang1) is a well-known angiogenic factor, its role in glucose homeostasis remains largely unknown. The objective of this study was to investigate whether and how Ang1 contributes to glucose homeostasis in response to metabolic challenge. We used inducible systemic Ang1-knockout (Ang1sys-/- ) and β-cell specific Ang1-knockout (Ang1β-cell-/- ) mice fed a high-fat diet for 24 weeks. Although the degree of insulin sensitivity did not differ between Ang1sys-/- versus Ang1sys+/+ mice, serum insulin levels were lower in Ang1sys-/- mice, resulting in significant glucose intolerance...
February 6, 2019: Diabetes
Hong Zhu, Bin Chen, Yi Cheng, Yin Zhou, Yi-Shang Yan, Qiong Luo, Ying Jiang, Jian-Zhong Sheng, Guo-Lian Ding, He-Feng Huang
Gestational diabetes mellitus (GDM) is associated with increased risk of metabolic disorders in offspring in later life. Although mounting evidence suggests that therapy for GDM could improve neonatal health, it is not known whether the therapy confers long-term metabolic benefits to offspring in their later adult lives. Here, using a mouse model of diabetes in the latter half of pregnancy to mimic human GDM, we find that the efficient insulin therapy of GDM confers significant protection against glucose intolerance and obesity in offspring fed on normal chow diet...
January 29, 2019: Diabetes
Dominic X Wang, Yuvreet Kaur, Akram Alyass, David Meyre
We hypothesized that monogenic syndromic obesity genes are also involved in the polygenic variation of BMI. Single-marker, tag single-nucleotide polymorphism (tagSNP), and gene-based analysis were performed on common variants near 54 syndromic obesity genes. We used publicly available data from meta-analyses of European BMI GWAS conducted by the Genetic Investigation of ANthropometric Traits (GIANT) consortium and the UK Biobank (UKB) (N=681,275 adults). A total of 33 genes were identified, of which 19/33 (57...
January 28, 2019: Diabetes
Patrick Shean-Young Lee, Nan Gao, Mamata Dike, Olga Shkilnyy, Rao Me, Yangyang Zhang, Fu-Shin X Yu
The diabetic cornea exhibits pathological alterations such as delayed epithelial wound healing and nerve regeneration. We sought to investigate the role of Semaphorin (SEMA) 3C in corneal wound healing and re-innervation in normal and diabetic B6 mice. Wounding induced the expression of SEMA3A, 3C and their receptor Neuropilin (NRP) 2, but not NRP1 in normal corneal epithelial cells (CECs); this upregulation was suppressed for SEMA3C and NRP2 in diabetic corneas. Injections of Sema3C- specific siRNA and NRP2 neutralizing antibodies in wounded mice resulted in a decrease in the rate of wound healing and regenerating nerve fibers, while exogenous SEMA3C had opposing effects in diabetic corneas...
January 24, 2019: Diabetes
Julien Vouillarmet, Audrey Josset-Lamaugarny, Paul Michon, Jean Louis Saumet, Audrey Koitka-Weber, Samir Henni, Berengere Fromy, Dominique Sigaudo-Roussel
Diabetic foot ulcer (DFU) is a problem worldwide and prevention is crucial. We hypothesized that the inability of the skin to respond to pressure is involved in DFU pathogenesis and could be an important predictive factor to take into account.We included 29 patients with DFU and 30 patients with type 2 diabetes without DFU. Neuropathy and skin blood flow at rest were assessed in response to acetylcholine, sodium nitroprusside, local heating (42°C), and to non-noxious locally applied pressure. Results were compared to those obtained from 10 healthy age-matched control subjects...
January 24, 2019: Diabetes
Kyung-Chul Moon, Hyun-Suk Suh, Ki-Bum Kim, Seung-Kyu Han, Ki-Won Young, Jin-Woo Lee
Mesenchymal stem cells (MSCs) may hold great promise for treating diabetic wounds. However, it is difficult for a clinician to use MSCs because they have not been commercialized. Meanwhile, a new commercial drug that contains adipose-derived stem cells (ASCs) has been developed. The purpose of this study was to examine the potential of allogeneic ASC sheets for treating diabetic foot ulcers. Fifty-nine patients with diabetic foot ulcers were randomized to either ASC treatment group (n = 30) or control group treated with polyurethane film (n = 29)...
January 24, 2019: Diabetes
Anna Syreeni, Niina Sandholm, Jingjing Cao, Iiro Toppila, David M Maahs, Marian J Rewers, Janet K Snell-Bergeon, Tina Costacou, Trevor J Orchard, M Luiza Caramori, Michael Mauer, Barbara E K Klein, Ronald Klein, Erkka Valo, Maija Parkkonen, Carol Forsblom, Valma Harjutsalo, Andrew D Paterson, Per-Henrik Groop
Glycated hemoglobin (HbA1c ) is an important measure of glycemia in diabetes. HbA1c is influenced by environmental and genetic factors, both in people with and without diabetes. We performed a genome-wide association study (GWAS) for HbA1c in a Finnish type 1 diabetes cohort, FinnDiane. Top results were examined for replication in type 1 diabetes cohorts DCCT/EDIC, WESDR, CACTI, EDC and RASS and a meta-analysis was performed. Three SNPs in high LD on chromosome 13 near relaxin family peptide receptor 2 ( RXFP2 ) were associated with HbA1c in FinnDiane at genome-wide significance (P <5×10-8 )...
January 23, 2019: Diabetes
Stephanie E Simonds, Jack T Pryor, Frank H Koegler, Alberte S Buch-Rasmussen, Lauren E Kelly, Kevin L Grove, Michael A Cowley
Liraglutide, a GLP-1 receptor agonist, and phentermine, a psychostimulant structurally related to amphetamine, are drugs approved for the treatment of obesity and hyperphagia. There is significant interest in combination use of liraglutide and phentermine for weight loss, however both drugs have been reported to induce systemic haemodynamic changes and as such the therapeutic window for this drug combination needs to be determined. To understand their impact on metabolic and cardiovascular physiology, we tested the effects of these drugs alone and in combination for 21 days in lean and obese male mice...
January 23, 2019: Diabetes
Seyed Mojtaba Ghiasi, Tina Dahlby, Caroline Hede Andersen, Leena Haataja, Sólrun Petersen, Muhmmad Omar-Hmeadi, Mingyu Yang, Celina Pihl, Sophie Emilie Bresson, Muhammad Saad Khilji, Kristian Klindt, Oana Cheta, Marcelo J Perone, Björn Tyrberg, Clara Prats, Sebastian Barg, Anders Tengholm, Peter Arvan, Thomas Mandrup-Poulsen, Michal Tomasz Marzec
Although endoplasmic reticulum (ER) chaperone binding to mutant proinsulin has been reported, the role of protein chaperones in the handling of wild-type proinsulin is under-investigated. Here, we have explored the importance of glucose regulated protein 94 (GRP94), a prominent ER chaperone known to fold insulin-like growth factors, in proinsulin handling within β-cells. We found that GRP94 co-immunoprecipitated with proinsulin and that inhibition of GRP94 function and/or expression reduced glucose-dependent insulin secretion, shortened proinsulin half-life and lowered intracellular proinsulin and insulin levels...
January 22, 2019: Diabetes
Lukas Huijbregts, Maja Borup Kjær Petersen, Claire Berthault, Mattias Hansson, Virginie Aiello, Latif Rachdi, Anne Grapin-Botton, Christian Honore, Raphael Scharfmann
Bromodomain and Extra-terminal (BET) proteins are epigenetic readers that interact with acetylated lysines of histone tails. Recent studies have demonstrated their role in cancer progression, as they recruit key components of the transcriptional machinery to modulate gene expression. However, their role during embryonic development of the pancreas has never been studied. Using mouse embryonic pancreatic explants and hiPSCs, we show that BET proteins inhibition with I-BET151 or JQ1 enhances the number of neurogenin3 endocrine progenitors...
January 17, 2019: Diabetes
Markus Hippich, Andreas Beyerlein, William A Hagopian, Jeffrey P Krischer, Kendra Vehik, Jan Knoop, Christiane Winker, Jorma Toppari, Åke Lernmark, Marian J Rewers, Andrea K Steck, Jin-Xiong She, Beena Akolkar, Catherine C Robertson, Suna Onengut-Gumuscu, Stephen S Rich, Ezio Bonifacio, Anette-G Ziegler
The risk for autoimmunity and subsequently type 1 diabetes is ten-fold higher in children with a first-degree family history of type 1 diabetes (FDR) than in the general population. We analyzed children with high-risk HLA genotypes (n=4,573) in the longitudinal TEDDY birth cohort to determine how much of the divergent risk is attributable to genetic enrichment in affected families. Enrichment for susceptible genotypes of multiple type 1 diabetes-associated genes and a novel risk gene, BTNL2 , were identified in FDR children as compared to general population children...
January 17, 2019: Diabetes
Qiqing Huang, Weiyan You, Yating Li, Yi Sun, Yuncai Zhou, Yan Zhang, Dechen Liu, Shanshan Zhan, Yunxia Zhu, Xiao Han
No abstract text is available yet for this article.
January 11, 2019: Diabetes
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