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Succinate diabetes

Marc-Emmanuel Dumas, Céline Domange, Sophie Calderari, Andrea Rodríguez Martínez, Rafael Ayala, Steven P Wilder, Nicolas Suárez-Zamorano, Stephan C Collins, Robert H Wallis, Quan Gu, Yulan Wang, Christophe Hue, Georg W Otto, Karène Argoud, Vincent Navratil, Steve C Mitchell, John C Lindon, Elaine Holmes, Jean-Baptiste Cazier, Jeremy K Nicholson, Dominique Gauguier
BACKGROUND: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus occurs through complex organ-specific cellular mechanisms and networks contributing to impaired insulin secretion and insulin resistance. Genome-wide gene expression profiling systems can dissect the genetic contributions to metabolome and transcriptome regulations. The integrative analysis of multiple gene expression traits and metabolic phenotypes (i.e., metabotypes) together with their underlying genetic regulation remains a challenge...
September 30, 2016: Genome Medicine
Maryam Chinisaz, Azadeh Ebrahim-Habibi, Ahmad-Reza Dehpour, Parichehreh Yaghmaei, Kazem Parivar, Ali Akbar Moosavi-Movahedi
Insulin is a therapeutic protein whose amyloid formation is reported in diabetic patients. Four anhydride compounds were used in the current study in order to experiment their potential reducing effect on insulin propensity to form amyloid fibrils. The modified forms (obtained with succinic-, 3,3-dimethylglutaric, 2-phenylglutaric-, and (2-Dodecen-1-yl) succinic anhydride), were first characterized with regard to melting temperature (Tm), changes in secondary structure percentage and hydrophobic surface. Fibril formation was then assessed by Congo red absorbance kinetics and transmission electron microscopy...
September 27, 2016: European Journal of Pharmaceutical Sciences
Brian D Fink, Fan Bai, Liping Yu, William I Sivitz
Recently, we used an ADP recycling approach to examine mouse skeletal muscle (SkM) mitochondrial function over respiratory states intermittent between state 3 and 4. We showed that respiration energized at complex II by succinate, in the presence of rotenone to block complex I, progressively increased with incremental additions of ADP. However, in the absence of rotenone, respiration peaked at low [ADP] but then dropped markedly as [ADP] was further increased. Here, we tested the hypothesis that these respiratory dynamics would differ between mitochondria of mice fed high-fat (HF) and treated with a low dose of streptozotocin to mimic type 2 diabetes and mitochondria from controls...
August 24, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Muhammad Tayyab Akhtar, Mohamad Syakir Bin Mohd Sarib, Intan Safinar Ismail, Faridah Abas, Amin Ismail, Nordin Hj Lajis, Khozirah Shaari
Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Ning Zhang, Fang Geng, Zhong-Hua Hu, Bin Liu, Ye-Qiu Wang, Jun-Cen Liu, Yong-Hua Qi, Li-Jing Li
OBJECTIVE: Comparative study of type 2 diabetes and healthy controls by metabolomics methods to explore the pathogenesis of Type II diabetes. METHODS: Gas chromatography - mass spectrometry (GC-MS) with a variety of multivariate statistical analysis methods to the healthy control group 58 cases, 68 cases of Type II diabetes group were analyzed. Chromatographic conditions: DB-5MS column; the carrier gas He; flow rate of 1 mL·min(-1), the injection volume 1 uL; split ratio is 100: 1...
2016: American Journal of Translational Research
Minjiang Chen, Hong Zheng, Tingting Wei, Dan Wang, Huanhuan Xia, Liangcai Zhao, Jiansong Ji, Hongchang Gao
Objective. High glucose- (HG-) induced neuronal cell death is responsible for the development of diabetic neuropathy. However, the effect of HG on metabolism in neuronal cells is still unclear. Materials and Methods. The neural-crest derived PC12 cells were cultured for 72 h in the HG (75 mM) or control (25 mM) groups. We used NMR-based metabolomics to examine both intracellular and extracellular metabolic changes in HG-treated PC12 cells. Results. We found that the reduction in intracellular lactate may be due to excreting more lactate into the extracellular medium under HG condition...
2016: BioMed Research International
Livia Roberta Piedade de Oliveira, Carla Martins, Tatiana Kelly Silva Fidalgo, Liana Bastos Freitas-Fernandes, Rafaela de Oliveira Torres, Aline Laignier Soares, Fabio C L Almeida, Ana Paula Valente, Ivete Pomarico Ribeiro de Souza
Metabolomics is an important tool for the evaluation of the human condition, in both health or disease. This study analyzed the salivary components of type I diabetic children (DM1) under six years of age, to assess oral health related to diabetes control, as well as metabolite profiling using NMR. Partial least squared discriminant analysis (PLS-DA) was used to compare healthy (HG) and uncontrolled DM1 subjects that demonstrated a separation between the groups with classificatory performance of ACC = 0.80, R(2) = 0...
August 5, 2016: Journal of Proteome Research
Qiang Jia, Shanfeng Ma, Xiaofen Liu, Sai Li, Yuanyuan Wang, Qin Gao, Rui Yang
OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on contraction capacity of diaphragm in type 1 diabetic rats.
 METHODS: Thirty-two male SD rats were randomly divided into a normal group (NC), a diabetic group (DM), a NaHS treatment group (DM+NaHS) and a NaHS group (NaHS) (n=8). Intraperitoneal injection of streptozotocin was utilized to establish diabetic rat model. After the modeling, the rats in the DM+NaHS and the NaHS groups were intraperitoneally injected with 28 μmol/kg NaHS solution...
May 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Abhishek Bhattacherjee, Kaliprasanna Dhara, Abhay Sankar Chakraborti
Diabetes mellitus represents a major metabolic disorder affecting millions of people all over the world. Currently available therapeutic treatments are not good enough to control the long-term complications of diabetes. Active targeting via inclusion of a specific ligand on the nanoparticles provides effective therapeutic approach in different diseases. However, such specific drug delivery systems have not been explored much in diabetes due to lack of suitable biological targets in this disorder. Our objective is to synthesize a ligand-tagged drug-loaded nanoparticle for delivery of the drug at specific sites to enhance its therapeutic efficiency in diabetic condition...
July 25, 2016: International Journal of Pharmaceutics
Ai Takemura, Akihiko Ishihara
Rats with type 2 diabetes exhibit decreased oxidative capacity, such as reduced oxidative enzyme activity, low-intensity staining for oxidative enzymes in fibers, and no high-oxidative type IIA fibers, in the skeletal muscle, especially in the soleus muscle. In contrast, there are no data available concerning the oxidative capacity of spinal motoneurons innervating skeletal muscle of rats with type 2 diabetes. This study examined the oxidative capacity of motoneurons innervating the soleus muscle of non-obese rats with type 2 diabetes...
September 2016: Neurochemical Research
Jose F Garcia-Mazcorro, David Mills, Giuliana Noratto
Diet affects gut microorganisms and dietary interventions can help treat obesity and overweight. Our aim was to investigate the effect of quinoa supplementation on fecal microbial ecology of obese diabetic mice. Obese db/db mice were fed commercial diets with and without quinoa supplementation for eight weeks; non-obese mice consuming non-supplemented diet served as lean-control. Fecal bacterial communities were analyzed using marker gene sequencing of 16S rRNA genes. Over 300 000 good-quality sequences were studied and assigned to 5774 different bacterial species (Operational Taxonomic Units at 97% similarity)...
July 2016: FEMS Microbiology Ecology
Bulbul Chakravarti, Chheten Sherpa, Devasrie Bose, Kakoli Paul Chowdhury, Kavita Khadar, Y Clare Zhang, Deb N Chakravarti
Type 1 diabetes (T1D) is a chronic autoimmune disease in which the pancreatic β-cells fail to produce insulin. In addition to such change in the endocrine function, the exocrine function of the pancreas is altered as well. To understand the molecular basis of the changes in both endocrine and exocrine pancreatic functions due to T1D, the proteome profile of the pancreas of control and diabetic mouse was compared using two dimensional gel electrophoresis (2D-GE) and the differentially expressed proteins identified by electrospray ionization liquid chromatography-tandem mass spectrometry (ESI-LC-MS/MS)...
April 25, 2016: Biochemical and Biophysical Research Communications
Neha Shrestha, Francisca Araújo, Mohammad-Ali Shahbazi, Ermei Mäkilä, Maria João Gomes, Mikko Airavaara, Esko I Kauppinen, Janne Raula, Jarno Salonen, Jouni Hirvonen, Bruno Sarmento, Hélder A Santos
Glucagon-like peptide-1 (GLP-1), an incretin hormone, is used for type 2 diabetes mellitus (T2DM) treatment because of its ability to stimulate insulin secretion and release in a glucose-dependent manner. Despite of its potent insulinotropic effect, oral GLP-1 delivery is greatly limited by its instability in the gastrointestinal tract, poor absorption efficiency and rapid degradation by dipeptidylpeptidase-4 (DPP4) enzyme leading to a short half-life (~2min). Thus, a multistage dual-drug delivery nanosystem was developed to deliver GLP-1 and DPP4 inhibitor simultaneously...
June 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Yongquan Zheng, Yunjun Yang, Baijun Dong, Hong Zheng, Xiaodong Lin, Yao Du, Xiaokun Li, Liangcai Zhao, Hongchang Gao
BACKGROUND: Diabetes-associated cognition decline is one of central nervous system complications in diabetic mellitus, while its pathogenic mechanism remains unclear. In this study, (1)H nuclear magnetic resonance-based metabonomics and immunohistochemistry was used to explore key metabolic alterations in hippocampus of type 2 diabetic db/db mice with cognition decline in order to advance understanding of mechanisms underlying the pathogenesis of the disease. RESULTS: Metabonomics reveals that lactate level was significantly increased in hippocampus of db/db mice with cognition decline compared with age-matched wild-type mice...
2016: Molecular Brain
Hong Zheng, Jinzi Wu, Zhen Jin, Liang-Jun Yan
Diabetes and its complications are hyperglycemic toxicity diseases. Many metabolic pathways in this array of diseases become aberrant, which is accompanied with a variety of posttranslational protein modifications that in turn reflect diabetic glucotoxicity. In this review, we summarize some of the most widely studied protein modifications in diabetes and its complications. These modifications include glycation, carbonylation, nitration, cysteine S-nitrosylation, acetylation, sumoylation, ADP-ribosylation, O-GlcNAcylation, and succination...
2016: Biochemistry Insights
I V Gatskikh, O F Veselova, I N Brikman, T P Shalda, E L Varygina, M N Kuznetsov, A V Shul'min, M M Petrova
Authors studied the efficacy of cytoflavin in the correction of cognitive impairment in patients with type 2 diabetes mellitus and the drug influence on the level of brain-derived neurotrophic factor (BDNF) in blood serum. The results of treatment and examination of 60 patients with type 2 diabetes diagnosis have been analyzed. The majority (49-81.6%) of patients initially exhibited light (35-71.4%) and moderate (14-28.6%) cognitive impairments. All patients received standard treatment with oral antidiabetic drugs: metformin monotherapy (26 patients or 43...
2015: Eksperimental'naia i Klinicheskaia Farmakologiia
Jose F Garcia-Mazcorro, Ivan Ivanov, David A Mills, Giuliana Noratto
The digestive tract of mammals and other animals is colonized by trillions of metabolically-active microorganisms. Changes in the gut microbiota have been associated with obesity in both humans and laboratory animals. Dietary modifications can often modulate the obese gut microbial ecosystem towards a more healthy state. This phenomenon should preferably be studied using dietary ingredients that are relevant to human nutrition. This study was designed to evaluate the influence of whole-wheat, a food ingredient with several beneficial properties, on gut microorganisms of obese diabetic mice...
2016: PeerJ
Lauren M Sparks, Anne Gemmink, Esther Phielix, Madeleen Bosma, Gert Schaart, Esther Moonen-Kornips, Johanna A Jörgensen, Emmani B M Nascimento, Matthijs K C Hesselink, Patrick Schrauwen, Joris Hoeks
AIMS/HYPOTHESIS: Dissipating energy via mitochondrial uncoupling has been suggested to contribute to enhanced insulin sensitivity. We hypothesised that skeletal muscle mitochondria of endurance-trained athletes have increased sensitivity for fatty acid (FA)-induced uncoupling, which is driven by the mitochondrial protein adenine nucleotide translocase 1 (ANT1). METHODS: Capacity for FA-induced uncoupling was measured in endurance-trained male athletes (T) and sedentary young men (UT) in an observational study and also in isolated skeletal muscle mitochondria from Zucker diabetic fatty (ZDF) rats and C2C12 myotubes following small interfering RNA (siRNA)-mediated gene silencing of ANT1...
May 2016: Diabetologia
Chao Li, Chengzhi Lu, Xiangdong Zhao, Xin Chen
This study aims to compare and analyze lactate dehydrogenase (LDH), succinic dehydrogenase (SDH) and differences in capillary density level in the model of myocardial damage which caused by rats diabetes. The Wistar rats were divided into 4 groups, including control, diabetic, myocardial infarction and two diseases combined group. Ligate descending branch of left coronary artery on 1/3 position or inject streptozotocin into abdominal cavity to establish two kinds of disease models. After 6 w, obtain the myocardial tissues to do the vascular density analysis of tissue sections which are stained and cell tissue enzyme...
2015: International Journal of Clinical and Experimental Medicine
Xiaoting Luo, Jinzi Wu, Siqun Jing, Liang-Jun Yan
Diabetes and its complications are caused by chronic glucotoxicity driven by persistent hyperglycemia. In this article, we review the mechanisms of diabetic glucotoxicity by focusing mainly on hyperglycemic stress and carbon stress. Mechanisms of hyperglycemic stress include reductive stress or pseudohypoxic stress caused by redox imbalance between NADH and NAD(+) driven by activation of both the polyol pathway and poly ADP ribose polymerase; the hexosamine pathway; the advanced glycation end products pathway; the protein kinase C activation pathway; and the enediol formation pathway...
January 2016: Aging and Disease
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