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lean diabetes

Pernille Wismann, Søren L Pedersen, Gitte Hansen, Karin Mannerstedt, Philip J Pedersen, Palle B Jeppesen, Niels Vrang, Keld Fosgerau, Jacob Jelsing
AIM: Analogues of several gastrointestinal peptide hormones have been developed into effective medicines for treatment of diseases such as type 2 diabetes mellitus (T2DM), obesity and short bowel syndrome (SBS). In this study, we aimed to explore whether the combination of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) into a potent co-agonist could provide additional benefits compared to existing monotherapies. METHODS: A short-acting (GUB09-123) and a half-life extended (GUB09-145) GLP-1/GLP-2 co-agonist were generated using solid-phase peptide synthesis and tested for effects on food intake, body weight, glucose homeostasis, and gut proliferation in lean mice and in diabetic db/db mice...
March 11, 2018: Physiology & Behavior
Silvia Barja-Fernandez, José María Moreno-Navarrete, Cintia Folgueira, Gemma Xifra, Mònica Sabater, Cecilia Castelao, Johan FernØ, Rosaura Leis, Carlos Diéguez, Felipe F Casanueva, Wifredo Ricart, Luisa M Seoane, José Manuel Fernandez-Real, Rubén Nogueiras
SCOPE: Angiopoietin-like protein 4 (ANGPTL-4) regulates plasma lipoprotein levels but its relevance in human obesity and type 2 diabetes is largely unknown. We aimed to investigate the regulation of circulating ANGPTL-4 levels in obesity, type 2 diabetes and after changes in body weight. METHODS AND RESULTS: Circulating ANGPTL-4 levels were measured in two different cohorts. First, in a cross-sectional study, we evaluated ANGPTL-4 levels in lean and obese patients with normoglycemia or with altered glucose tolerance (n = 282)...
March 14, 2018: Molecular Nutrition & Food Research
Xin Qian, Hui Wang, Gangyi Yang, Zhengnan Gao, Yong Luo, Aimei Dong, Fang Zhang, Mingtong Xu, Shiping Liu, Xin Yang, Yanyan Chen, Guangwei Li
INTRODUCTION: To investigate the effects of pioglitazone (PIO) on insulin resistance and first phase insulin secretion among obese and lean Chinese people with type 2 diabetes mellitus (T2DM). METHODS: Sixty-eight drug-naïve patients with T2DM were treated with PIO for 16 weeks. Before and after the treatment, insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test. Plasma insulin levels at 0, 3, 5, 7, and 10 min during intravenous glucose tolerance test were determined to calculate the first phase insulin secretion and pancreatic β-cell function...
March 13, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Tianyi Qiu, Min Li, Miles A Tanner, Yan Yang, James R Sowers, Ronald J Korthuis, Michael A Hill
BACKGROUND: Accumulation of multiple subtypes of immune cells in perivascular adipose tissue (PVAT) has been proposed to cause vascular inflammation and dysfunction in type 2 diabetes (T2DM). This study was designed to investigate specific roles for dendritic cells in PVAT in the development of vascular inflammation and impaired PVAT-mediated vasorelaxation in T2DM. METHODS AND RESULTS: Studies were performed using db/db mice (model of T2DM) and their Db heterozygote (DbHET), lean and normoglycemic controls...
March 9, 2018: Metabolism: Clinical and Experimental
Hao Shi, Alexander Munk, Thomas S Nielsen, Morgan R Daughtry, Louise Larsson, Shize Li, Kasper F Høyer, Hannah W Geisler, Karolina Sulek, Rasmus Kjøbsted, Taylor Fisher, Marianne M Andersen, Zhengxing Shen, Ulrik K Hansen, Eric M England, Zhiyong Cheng, Kurt Højlund, Jørgen F P Wojtaszewski, Xiaoyong Yang, Matthew W Hulver, Richard F Helm, Jonas T Treebak, David E Gerrard
OBJECTIVE: Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. METHODS: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry...
February 24, 2018: Molecular Metabolism
Joseph Wider, Vishnu V R Undyala, Peter Whittaker, James Woods, Xuequn Chen, Karin Przyklenk
Remote ischemic preconditioning (RIPC), the phenomenon whereby brief ischemic episodes in distant tissues or organs render the heart resistant to infarction, has been exhaustively demonstrated in preclinical models. Moreover, emerging evidence suggests that exosomes play a requisite role in conveying the cardioprotective signal from remote tissue to the myocardium. However, in cohorts displaying clinically common comorbidities-in particular, type-2 diabetes-the infarct-sparing effect of RIPC may be confounded for as-yet unknown reasons...
March 9, 2018: Basic Research in Cardiology
Jill K Badin, Ayeeshik Kole, Benjamin Stivers, Victor Progar, Anisha Pareddy, Mouhamad Alloosh, Michael Sturek
BACKGROUND: There is a preponderance of evidence implicating diabetes with increased coronary artery disease (CAD) and calcification (CAC) in human patients with metabolic syndrome (MetS), but the effect of diabetes on CAD severity in animal models remains controversial. We investigated whether diabetes exacerbates CAD/CAC and intracellular free calcium ([Ca2+ ]i ) dysregulation in the clinically relevant Ossabaw miniature swine model of MetS. METHODS: Sixteen swine, eight with alloxan-induced diabetes, were fed a hypercaloric, atherogenic diet for 6 months...
March 9, 2018: Journal of Translational Medicine
Emil Andersen, Lars Roed Ingerslev, Odile Fabre, Ida Donkin, Ali Altıntaş, Soetkin Versteyhe, Thue Bisgaard, Viggo B Kristiansen, David Simar, Romain Barrès
BACKGROUND: Deterioration of the adipogenic potential of preadipocytes may contribute to adipose tissue dysfunction in obesity and type 2 diabetes (T2D). Here, we hypothesized that extracellular factors in obesity epigenetically reprogram adipogenesis potential and metabolic function of preadipocytes. METHODS: The transcriptomic profile of visceral adipose tissue preadipocytes collected from Lean, Obese and Obese with T2D was assessed throughout in vitro differentiation using RNA sequencing...
February 20, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Valentina Caracciolo, Jeanette Young, Donna Gonzales, Yinchun Ni, Stephen J Flowers, Ross Summer, Scott A Waldman, Jason K Kim, Dae Young Jung, Hye Lim Noh, Taekyoon Kim, Perry J Blackshear, Danielle O'Connell, Robert C Bauer, Caleb B Kallen
Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc Finger Protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild type (Control) mice became obese and diabetic on a high-fat diet and obese mice with myeloid-specific loss of Zfp36 (KO) demonstrated increased adipose tissue and liver cytokine mRNA expression compared to Control mice...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
R Dev, E Bruera, S Dalal
Cancer cachexia, weight loss with altered body composition, is a multifactorial syndrome propagated by symptoms that impair caloric intake, tumor byproducts, chronic inflammation, altered metabolism, and hormonal abnormalities. Cachexia is associated with reduced performance status, decreased tolerance to chemotherapy, and increased mortality in cancer patients. Insulin resistance as a consequence of tumor byproducts, chronic inflammation, and endocrine dysfunction has been associated with weight loss in cancer patients...
February 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Guillaume P Andrieu, Jordan S Shafran, Jude T Deeney, Kishan R Bharadwaj, Annapoorni Rangarajan, Gerald V Denis
Obesity and its associated pathology Type 2 diabetes are two chronic metabolic and inflammatory diseases that promote breast cancer progression, metastasis, and poor outcomes. Emerging critical opinion considers unresolved inflammation and abnormal metabolism separately from obesity; settings where they do not co-occur can inform disease mechanism. In breast cancer, the tumor microenvironment is often infiltrated with T effector and T regulatory cells programmed by metabolic signaling. The pathways by which tumor cells evade immune surveillance, immune therapies, and take advantage of antitumor immunity are poorly understood, but likely depend on metabolic inflammation in the microenvironment...
March 1, 2018: Journal of Leukocyte Biology
Surya N Mulukutla, Jean W Hsu, Ruchi Gaba, Kurt M Bohren, Anu Guthikonda, Dinakar Iyer, Nadim J Ajami, Joseph F Petrosino, Christiane S Hampe, Nalini Ram, Farook Jahoor, Ashok Balasubramanyam
Background: A-β + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible β cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved. Objective: The objective of this study was to determine the relation between gut microbiome and arginine metabolism and the relation between arginine availability and β cell function in KPD patients compared with control participants...
February 1, 2018: Journal of Nutrition
Aimo Kannt, Sridharan Rajagopal, Sanjay Venkatachalapathi Kadnur, Juluri Suresh, Ravi Kanth Bhamidipati, Srinivasan Swaminathan, Mahanandeesha Siddappa Hallur, Rajendra Kristam, Ralf Elvert, Jörg Czech, Anja Pfenninger, Christine Rudolph, Herman Schreuder, Devaraj Venkatapura Chandrasekar, Vishal Subhash Mane, Swarnakumari Birudukota, Shama Shaik, Bharat Ravindra Zope, Raghunadha Reddy Burri, Niranjan Naranapura Anand, Manish Kumar Thakur, Manvi Singh, Reejuana Parveen, Saravanan Kandan, Ramesh Mullangi, Takeshi Yura, Ramachandraiah Gosu, Sven Ruf, Saravanakumar Dhakshinamoorthy
Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease...
February 26, 2018: Scientific Reports
Roya Mahdavi, Samira Ghorbani, Behnam Alipoor, Ghodratollah Panahi, Hadi Khodabandehloo, Ensieh Nasli Esfahani, Farideh Razi, Reza Meshkani
BACKGROUND: Type 2 diabetes is the most common metabolic disease, affecting many of the adult population all around the world. In recent years much attention has been paid to the role of circulating miRNAs as novel biomarkers for various diseases. The aim of this study was to investigate the expression level of miR-155 in serum samples of diabetic and healthy subjects. METHODS: 42 healthy and 45 type 2 diabetic subjects participated in the study. Serum miR-155 level of the subjects was measured using real-time PCR...
January 1, 2018: Clinical Laboratory
Simon Göddeke, Birgit Knebel, Pia Fahlbusch, Tina Hörbelt, Gereon Poschmann, Frederique van de Velde, Tim Benninghoff, Hadi Al-Hasani, Sylvia Jacob, Yves Van Nieuwenhove, Bruno Lapauw, Stefan Lehr, D Margriet Ouwens, Jorg Kotzka
BACKGROUND: CDH13, an atypical member of the cadherin superfamily, has been identified in adipocyte secretomes of lean mouse models. CDH13 abundance differs in mouse models according to their susceptibility to develop metabolic disorders, but the role of CDH13 in adipose tissue is unknown. METHODS: Secreted CDH13 protein levels and mRNA levels in visceral adipose tissue were determined in lean and obese mouse models. In vitro studies were performed in 3T3-L1 adipocytes to determine the role of CDH13 in adipocyte differentiation...
February 21, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Bogna Grygiel-Górniak, Elżbieta Kaczmarek, Maria Mosor, Juliusz Przysławski, Jerzy Nowak
As ageing and increased body fat are the signs of insulin resistance, we have studied whether the presence of Pro12Ala and C1431T of peroxisome proliferator-activated receptor gamma 2 gene and Trp64Arg of beta 3-adrenergic receptor gene may predispose to the hyperglycaemia development in postmenopausal women, who have never undergone hypoglycaemic treatment. The distributions of selected allele and genotype frequencies were determined by the PCR-RFLP method in normo- and hyperglycaemic, who have never been diagnosed and treated for diabetes mellitus were measured...
February 20, 2018: Journal of Applied Genetics
Caifeng Yan, Jin Li, Shangyong Feng, Ying Li, Lu Tan
Long non-coding RNA Gomafu is involved in diabetes-related diseases. However, its role in insulin resistance (IR) remains unclear. Our objective is to explore the role of Gomafu in hepatic IR and glucose intolerance. Gomafu expression was determined in livers of ob/ob mice and high-fat diet (HFD) mice. The binding activity of NF-κB on the Gomafu promoter was measured by chromatin immunoprecipitation and quantitative real-time PCR assays. Increased Gomafu expression was observed in the livers of obese mice...
February 19, 2018: Cell Death & Disease
Simon A Hinke, Anne M Cieniewicz, Thomas Kirchner, Katharine D'Aquino, Rupesh Nanjunda, Jason Aligo, Robert Perkinson, Philip Cooper, Ken Boayke, Mark L Chiu, Steve Jarantow, Eilyn R Lacy, Yin Liang, Dana L Johnson, Jean M Whaley, Russell B Lingham, Anthony J Kihm
OBJECTIVE: Insulin resistance is a key feature of Type 2 Diabetes (T2D), and improving insulin sensitivity is important for disease management. Allosteric modulation of the insulin receptor (IR) with monoclonal antibodies (mAbs) can enhance insulin sensitivity and restore glycemic control in animal models of T2D. METHODS: A novel human mAb, IRAB-A, was identified by phage screening using competition binding and surface plasmon resonance assays with the IR extracellular domain...
February 3, 2018: Molecular Metabolism
Jon D Oden, Brian Franklin, Ernesto Fernandez, Soumya Adhikari, Perrin C White
BACKGROUND: Body mass index (BMI) and fat mass may be higher in children with diabetes compared to healthy peers. It is not certain how diabetic children respond to exercise and diet interventions. OBJECTIVE: To investigate the effect of summer camp on BMI and body composition in children with type 1 diabetes. METHODS: Five hundred eighty-six children (5-19 years, 518 with type 1 diabetes, 68 without diabetes) were followed while attending camp...
February 13, 2018: Pediatric Diabetes
Neeraj Chandrahas Deshpande, Mansi Rajendrakumar Amrutiya
Introduction: Periodontitis is defined as a destructive inflammatory disease involving the supporting tissues of the teeth due to specific microorganisms which results in a progressive destruction of supporting structures of the periodontium. Obesity is excessive body fat in proportion to lean body mass, to such an extent that health is impaired. Obesity, a serious public health problem, relates to a chronic low-grade systemic inflammation and is involved in the development of obesity-linked disorders including insulin resistance, type 2 diabetes, cardiovascular diseases, dyslipidemia, and metabolic syndrome...
May 2017: Journal of Indian Society of Periodontology
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