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https://www.readbyqxmd.com/read/28239846/inhibition-of-6-phosphofructo-2-kinase-suppresses-fibroblast-like-synoviocytes-mediated-synovial-inflammation-and-joint-destruction-in-rheumatoid-arthritis
#1
Yaoyao Zou, Shan Zeng, Mingcheng Huang, Qian Qiu, Youjun Xiao, Maohua Shi, Zhongping Zhan, Liuqin Liang, Xiuyan Yang, Hanshi Xu
BACKGROUND AND PURPOSE: Abnormal glycolytic metabolism contributes to joint inflammation in rheumatoid arthritis (RA). The aims of this study were to investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a bifunctional enzyme that controls the glycolytic rate, in regulating fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and invasiveness in RA. EXPERIMENTAL APPROACH: A specific PFKFB3 inhibitor, PFK15, and siRNA were used to evaluate the role of PFKFB3...
February 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28238841/vitamin-a-status-affects-the-plasma-parameters-and-regulation-of-hepatic-genes-in-streptozotocin-induced-diabetic-rats
#2
Yang Li, Yang Liu, Guoxun Chen
Vitamin A (VA) status regulates metabolism in rats. Whether VA status and availability of retinoic acid (RA) contribute to the insulin-regulated hepatic gene expression remains to be determined. Zucker lean rats with VA sufficient (VAS) or VA deficient (VAD) status were treated with streptozotocin (STZ) to induce insulin-dependent diabetes. They were treated with saline (STZ-VAS-C or STZ-VAD-C), RA (STZ-VAS-RA or STZ-VAD-RA), insulin (STZ-VAS-INS or STZ-VAD-INS), or insulin + RA (STZ-VAS-INS+RA or STZ-VAD-INS+RA) for 3 hours...
February 23, 2017: Biochimie
https://www.readbyqxmd.com/read/28238783/visualization-of-glucagon-secretion-from-pancreatic-%C3%AE-cells-by-bioluminescence-video-microscopy-identification-of-secretion-sites-in-the-intercellular-contact-regions
#3
Satoru Yokawa, Takahiro Suzuki, Satoshi Inouye, Yoshikazu Inoh, Ryo Suzuki, Takao Kanamori, Tadahide Furuno, Naohide Hirashima
We have firstly visualized glucagon secretion using a method of video-rate bioluminescence imaging. The fusion protein of proglucagon and Gaussia luciferase (PGCG-GLase) was used as a reporter to detect glucagon secretion and was efficiently expressed in mouse pancreatic α cells (αTC1.6) using a preferred human codon-optimized gene. In the culture medium of the cells expressing PGCG-GLase, luminescence activity determined with a luminometer was increased with low glucose stimulation and KCl-induced depolarization, as observed for glucagon secretion...
February 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28238701/deep-brain-stimulation-of-the-subcallosal-cingulate-for-treatment-refractory-anorexia-nervosa-1-year-follow-up-of-an-open-label-trial
#4
Nir Lipsman, Eileen Lam, Matthew Volpini, Kalam Sutandar, Richelle Twose, Peter Giacobbe, Devin J Sodums, Gwenn S Smith, D Blake Woodside, Andres M Lozano
BACKGROUND: Anorexia nervosa is a life-threatening illness. Brain circuits believed to drive anorexia nervosa symptoms can be accessed with surgical techniques such as deep brain stimulation (DBS). Initial results suggest that DBS of the subcallosal cingulate is safe and associated with improvements in mood and anxiety. Here, we investigated the safety, clinical, and neuroimaging outcomes of DBS of the subcallosal cingulate in a group of patients during 12 months of active stimulation...
February 23, 2017: Lancet Psychiatry
https://www.readbyqxmd.com/read/28238066/crocin-inhibits-oxidative-stress-and-pro-inflammatory-response-of-microglial-cells-associated-with-diabetic-retinopathy-through-the-activation-of-pi3k-akt-signaling-pathway
#5
Xinguang Yang, Fuquan Huo, Bei Liu, Jing Liu, Tao Chen, Junping Li, Zhongqiao Zhu, Bochang Lv
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus that is closely associated with the degeneration and loss of retinal ganglion cells (RGCs) caused by diabetic microangiopathy and subsequent oxidative stress and an inflammatory response. Microglial cells are classed as neurogliocytes and play a significant role in neurodegenerative diseases. Over-activated microglial cells may cause neurotoxicity and induce the death and apoptosis of RGCs. Crocin is one of the two most pharmacologically bioactive constituents in saffron...
February 25, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28237848/il-17-axis-accelerates-the-inflammatory-progression-of-obese-in-mice-via-tbk1-and-ikbke-pathway
#6
Seung Hoon Lee, JooYeon Jhun, Jae-Kyung Byun, Eun-Kyung Kim, KyoungAh Jung, Ji Eun Lee, Jong Young Choi, Sung-Hwan Park, Mi-La Cho
Obesity mediates immune inflammatory response and induces IL-17 expression. Adipgenesis can be regulated by IL-17 and it causes TBK1 activation. The inhibition of TBK1 and the inhibition of I IKBKE reduces inflammatory response and improves obesity. It is hypothesized that IL-17 deficiency inhibits obesity progression and inflammation. 3T3-L1 preadipocytes were differentiated in vitro and treated with IL-17. RAW264.7 cells and differentiated 3T3-L1 were pretreated with TBK1 inhibitor and then stimulated with IL-17...
February 22, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28237679/pectin-lyase-overproduction-by-penicillium-griseoroseum-mutants-resistant-to-catabolite-repression
#7
Juliana Oliveira Lima, Jorge Fernando Pereira, Elza Fernandes de Araújo, Marisa Vieira de Queiroz
Expression of pectinolytic genes is regulated by catabolic repression limiting the production of pectin lyase (PL) if the natural inducer, pectin, is missing from the growth medium. Here, we report the isolation of Penicillium griseoroseum mutants resistant to 2-deoxy-d-glucose (DG) that show resistance to catabolite repression and overproduce PL. Three spontaneous and nine UV-induced mutants were obtained. Some mutants produced sectors (segments morphologically different) that were also studied. The mutants were analyzed for pectinases production on pectinase-agar plates and five mutants and two sectors showing larger clearing zones than the wild type were selected for quantitative assay...
February 9, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28237649/protein-kinase-ck2%C3%AE-catalytic-subunit-ameliorates-diabetic-renal-inflammatory-fibrosis-via-nf-%C3%AE%C2%BAb-signaling-pathway
#8
Junying Huang, Zhiquan Chen, Jie Li, Qiuhong Chen, Jingyan Li, Wenyan Gong, Jiani Huang, Peiqing Liu, Heqing Huang
Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2α ameliorates renal inflammatory fibrosis in diabetes via NF-κB pathway. To explore potential regulatory mechanism of CK2α, the expression and activity of CK2α, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA)...
February 22, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28237576/glucose-derived-ages-promote-migration-and-invasion-of-colorectal-cancer-by-up-regulating-sp1-expression
#9
Ruyuan Deng, Huo Wu, Hui Ran, Xiang Kong, Lei Hu, Xiao Wang, Qing Su
It is well established that the risk of colorectal cancer (CRC) is significantly increased in diabetic patients. As one of main forms of the advanced glycation end products (AGEs) that accumulate in vivo, glucose-derived AGEs play an important role in the pathogenesis of diabetic complications and may contribute to CRC progression. However, to date, both the contribution of glucose-derived AGEs to the course of CRC and the underlying mechanism are unclear. In the present study, the concentration of glucose-derived AGEs in the serum and tumor tissue of patients with CRC increased...
February 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28237320/a-perspective-on-metabolic-surgery-from-a-gastroenterologist
#10
REVIEW
Yu-Fong Syu, Akio Inui, Chih-Yen Chen
Type 2 diabetes (T2D) and obesity are important public health problems. The global prevalence of diabetes mellitus is 8.8%. Interventional diabetology and obesitology have been recently advocated as treatment options for T2D and obesity. The roles of metabolic surgery such as Roux-en-Y gastric bypass, sleeve gastrectomy, gastric banding, and biliopancreatic diversion are focused. Different types of metabolic surgeries have different glucose-lowering and weight loss effects. Endoscopic treatments include the intra-gastric balloon (to restrict the gastric volume) and duodenal-jejunal bypass liner (DJBL, as a malabsorptive procedure)...
January 19, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28236654/sortilin-1-knockout-alters-basal-adipose-glucose-metabolism-but-not-diet-induced-obesity-in-mice
#11
Jibiao Li, David J Matye, Yifeng Wang, Tiangang Li
Sortilin 1 (Sort1) is a trafficking receptor that has been implicated in the regulation of plasma cholesterol in humans and mice. Here, we use metabolomics and hyperinsulinemic-euglycemic clamp approaches to obtain further understanding of the in vivo effects of Sort1 deletion on diet-induced obesity as well as on adipose lipid and glucose metabolism. Results show that Sort1 knockout does not affect Western diet-induced obesity or adipose fatty acid and ceramide concentrations. Under the basal fasting state, chow-fed Sort1 knockout mice have decreased adipose glycolytic metabolites, but Sort1 deletion does not affect insulin-stimulated tissue glucose uptake during the insulin clamp...
February 25, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28236525/role-of-serum-adiponectin-and-vitamin-d-in-prediabetes-and-diabetes-mellitus
#12
Anindita Banerjee, Vineet Kumar Khemka, Debashree Roy, Jit Poddar, Tapan Kumar Sinha Roy, Srikanth Arliganur Karnam
OBJECTIVES: The roles of deficient or deranged insulin, adiponectin and 25 hydroxy vitamin D (25[OH]D) levels regulating food intake, energy metabolism, glucose and lipid metabolism and body weight have been reported in the pathogenesis of prediabetes and type 2 diabetes mellitus. However, their congruity in the etiology of diabetes mellitus is unknown. Thus, the aim of the study was to investigate the roles of these parameters together and to establish their interrelationship in patients with prediabetes and diabetes...
February 21, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28236429/adiponectin-improves-endothelial-function-in-mesenteric-arteries-of-high-fat-fed-wistar-rats-role-of-perivascular-adipose-tissue
#13
Cristina M Sena, Ana Pereira, Rosa Fernandes, Liliana Letra, Raquel M Seiça
BACKGROUND AND PURPOSE: Adiponectin, the most abundant peptide secreted by adipocytes, is involved in the regulation of energy metabolism and vascular physiology. Thus, we investigated the effects of exogenous administration of adiponectin on metabolism, vascular reactivity and perivascular adipose tissue (PVAT) of rat mesenteric arteries in high-fat fed Wistar rats. EXPERIMENTAL APPROACH: The effects of adiponectin were investigated on nitric oxide (NO)-dependent and independent vasorelaxation in isolated rat mesenteric arteries from 12-month-old male Wistar rats fed with high-fat diet during 4 months (HFD) and compared with age-matched control Wistar rats (W12m)...
February 25, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28236404/petroleum-ether-sub-fraction-of-rosemary-extract-improves-hyperlipidemia-and-insulin-resistance-by-inhibiting-srebps
#14
Zhi-Shen Xie, Ling-Jun Zhong, Xiao-Meng Wan, Meng-Ning Li, Hua Yang, Ping Li, Xiao-Jun Xu
As a culinary and medicinal herb, rosemary is widely used. The present work aimed to investigate the effects of rosemary extracts on metabolic diseases and the underlying mechanisms of action. Liver cells stably expressing SREBP reporter were used to evaluate the inhibitory effects of different fractions of rosemary extracts on SREBP activity. The obese mice induced by Western-type diet were orally administered with rosemary extracts or vehicle for 7 weeks, the plasma and tissue lipids were analyzed. SREBPs and their target genes were measured by quantitative RT-PCR...
October 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28235959/insulin-resistance-and-prognosis-of-nondiabetic-patients-with-ischemic-stroke-the-across-china-study-abnormal-glucose-regulation-in-patients-with-acute-stroke-across-china
#15
Jing Jing, Yuesong Pan, Xingquan Zhao, Huaguang Zheng, Qian Jia, Donghua Mi, Weiqi Chen, Hao Li, Liping Liu, Chunxue Wang, Yan He, David Wang, Yilong Wang, Yongjun Wang
BACKGROUND AND PURPOSE: Insulin resistance was common in patients with stroke. This study investigated the association between insulin resistance and outcomes in nondiabetic patients with first-ever acute ischemic stroke. METHODS: Patients with ischemic stroke without history of diabetes mellitus in the ACROSS-China registry (Abnormal Glucose Regulation in Patients With Acute Stroke Across China) were included. Insulin resistance was defined as a homeostatis model assessment-insulin resistance (HOMA-IR) index in the top quartile (Q4)...
February 24, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28235848/patients-with-long-qt-syndrome-due-to-impaired-herg-encoded-kv11-1-potassium-channel-have-exaggerated-endocrine-pancreatic-and-incretin-function-associated-with-reactive-hypoglycemia
#16
Louise Hyltén-Cavallius, Eva W Iepsen, Nicolai J Wewer Albrechtsen, Mathilde Svendstrup, Anniek F Lubberding, Bolette Hartmann, Thomas Jespersen, Allan Linneberg, Michael Christiansen, Henrik Vestergaard, Oluf Pedersen, Jens J Holst, Jørgen K Kanters, Torben Hansen, Signe S Torekov
Background -Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long QT syndrome (LQT2) due to prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and β cells and intestinal L and K cells, secreting glucagon, insulin, and the incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), respectively. These hormones are crucial for glucose regulation and LQTS may cause disturbed glucose regulation. We measured secretion of these hormones and cardiac repolarization in response to glucose ingestion in LQT2 patients with functional mutations in hERG and matched healthy participants, testing the hypothesis that LQT2 patients have increased incretin and β cell- and decreased α cell function and thus lower glucose levels...
February 24, 2017: Circulation
https://www.readbyqxmd.com/read/28235788/systems-genetics-approach-identifies-trp53inp2-as-a-link-between-cardiomyocyte-glucose-utilization-and-hypertrophic-response
#17
Marcus M Seldin, Eric D Kim, Milagros C Romay, Shen Li, Christoph D Rau, Jessica J Wang, Karthickeyan Chella Krishnan, Yibin Wang, Arjun Deb, Aldons J Lusis
Cardiac failure has been widely associated with an increased glucose utilization. The aim of our present study was to identify factors which mechanistically bridge this link between hyperglycemia and heart failure. Here, we screened the Hybrid Mouse Diversity Panel (HMDP) for substrate-specific cardiomyocyte candidates based on heart transcriptional profile and circulating nutrients. Next, we utilized an in vitro model of rat cardiomyocytes to demonstrate that the gene expression changes were in direct response to substrate abundance...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28235722/current-trend-in-drug-delivery-considerations-for-subcutaneous-insulin-depots-to-treat-diabetes
#18
REVIEW
Jayakrishnapillai P V, Shantikumar V Nair, Kaladhar Kamalasanan
Diabetes mellitus (DM) is a metabolic disorder due to irregularities in glucose metabolism, as a result of insulin disregulation. Chronic DM (Type 1) is treated by daily insulin injections by subcutaneous route. Daily injections cause serious patient non-compliance and medication non-adherence. Insulin Depots (ID) are parenteral formulations designed to release the insulin over a specified period of time, to control the plasma blood glucose level for intended duration. Physiologically, pancreas produces and secretes insulin in basal and pulsatile mode into the blood...
February 17, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28235645/modification-of-the-fatty-acid-composition-of-an-obesogenic-diet-improves-the-maternal-and-placental-metabolic-environment-in-obese-pregnant-mice
#19
Martina Gimpfl, Jan Rozman, Maik Dahlhoff, Raphaela Kübeck, Andreas Blutke, Birgit Rathkolb, Martin Klingenspor, Martin Hrabě de Angelis, Soner Öner-Sieben, Annette Seibt, Adelbert A Roscher, Eckhard Wolf, Regina Ensenauer
Peri-conceptional exposure to maternal obesogenic nutrition is associated with in utero programming of later-life overweight and metabolic disease in the offspring. We aimed to investigate whether dietary intervention with a modified fatty acid quality in an obesogenic high-calorie (HC) diet during the preconception and gestational phases can improve unfavourable effects of an adipogenic maternal environment. In NMRI mice, peri-conceptional and gestational obesity was induced by feeding a HC diet (controls), and they were compared with dams on a fat-modified (Fat-mod) HC diet of the same energy content but enriched with medium-chain fatty acids (MCFAs) and adjusted to a decreased ratio of n-6 to n-3 long-chain polyunsaturated fatty acids (LC-PUFAs)...
February 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28235644/down-regulation-of-the-mitochondrial-aspartate-glutamate-carrier-isoform-1-agc1-inhibits-proliferation-and-n-acetylaspartate-synthesis-in-neuro2a-cells
#20
Emanuela Profilo, Luis Emiliano Peña-Altamira, Mariangela Corricelli, Alessandra Castegna, Alberto Danese, Gennaro Agrimi, Sabrina Petralla, Giulia Giannuzzi, Vito Porcelli, Luigi Sbano, Carlo Viscomi, Francesca Massenzio, Erika Mariana Palmieri, Carlotta Giorgi, Giuseppe Fiermonte, Marco Virgili, Luigi Palmieri, Massimo Zeviani, Paolo Pinton, Barbara Monti, Ferdinando Palmieri, Francesco Massimo Lasorsa
The mitochondrial aspartate-glutamate carrier isoform 1 (AGC1) catalyzes a Ca(2+)-stimulated export of aspartate to the cytosol in exchange for glutamate, and is a key component of the malate-aspartate shuttle which transfers NADH reducing equivalents from the cytosol to mitochondria. By sustaining the complete glucose oxidation, AGC1 is thought to be important in providing energy for cells, in particular in the CNS and muscle where this protein is mainly expressed. Defects in the AGC1 gene cause AGC1 deficiency, an infantile encephalopathy with delayed myelination and reduced brain N-acetylaspartate (NAA) levels, the precursor of myelin synthesis in the CNS...
February 21, 2017: Biochimica et Biophysica Acta
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