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https://www.readbyqxmd.com/read/28217809/-generation-and-phenotype-analysis-of-zebrafish-mutations-of-obesity-related-genes-lepr-and-mc4r
#1
Fei Fei, Shao-Yang Sun, Yu-Xiao Yao, Xu Wang
Obesity has become a severe public health problem across the world, and seriously affects the health and life quality of human beings. Here we generated lepr and mc4r mutant zebrafish via the CRISPR/Cas9 technique, and performed morphological and functional characterizations of those mutants. We observed that there was no significant phenotypic difference between homozygous mutants and wild-type controls before 2.5 months post-fertilization (mpf). However, the adult lepr(-/-) and mc4r(-/-) individuals displayed increased food intake, heavier weight, and higher body fat percentage, the characteristics of obesity phenotypes...
February 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28213512/27-hydroxycholesterol-impairs-neuronal-glucose-uptake-through-an-irap-glut4-system-dysregulation
#2
Muhammad-Al-Mustafa Ismail, Laura Mateos, Silvia Maioli, Paula Merino-Serrais, Zeina Ali, Maria Lodeiro, Eric Westman, Eran Leitersdorf, Balázs Gulyás, Lars Olof-Wahlund, Bengt Winblad, Irina Savitcheva, Ingemar Björkhem, Angel Cedazo-Mínguez
Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced (18)F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)-mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N)...
February 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28213107/hypoglycemic-effect-of-the-polyphenols-rich-extract-from-rose-rugosa-thunb-on-high-fat-diet-and-stz-induced-diabetic-rats
#3
Liu Liu, Dan Tang, Haiqing Zhao, Xuelei Xin, Haji Akber Aisa
ETHNOPHARMACOLOGICAL RELEVANCE: Rosa rugosa Thunb is traditional Uygur medicine, it is widely used for regulating blood condition, nourishing liver and gallbladder in Uygur ancient prescription. But the mechanism of Rosa rugosa Thunb on diabetes is still unclear. In here, we studied the hypoglycemic effect and explained one probable pathway of polyphenols rich extract from Rosa rugosa Thunb (RPE) on diabetic rats. MATERIALS AND METHODS: In vitro, the effect of RPE on α-glucosidase inhibition was finished, and the antioxidant activity of RPE was evaluated by ABTS and DPPH assay...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28202581/identification-and-functional-implications-of-sodium-myo-inositol-cotransporter-1-in-pancreatic-beta-cells-and-type-2-diabetes-mellitus
#4
Stephen Yu Ting Li, Sam Tsz Wai Cheng, Dan Zhang, Po Sing Leung
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28199386/associations-of-lipid-profiles-with-insulin-resistance-and-%C3%AE-cell-function-in-adults-with-normal-glucose-tolerance-and-different-categories-of-impaired-glucose-regulation
#5
Shuang Zheng, Hua Xu, Huan Zhou, Xingxing Ren, Tingting Han, Yawen Chen, Huiying Qiu, Peihong Wu, Jun Zheng, Lihua Wang, Wei Liu, Yaomin Hu
AIMS: To investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR). METHODS: 544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function...
2017: PloS One
https://www.readbyqxmd.com/read/28189115/n-3-polyunsaturated-fatty-acids-alleviate-high-glucose-mediated-dysfunction-of-endothelial-progenitor-cells-and-prevent-ischemic-injuries-both-in-vitro-and-in-vivo
#6
Shao-Chih Chiu, Che-Yi Chao, En-Pei Isabel Chiang, Jia-Ning Syu, Raymond L Rodriguez, Feng-Yao Tang
Hyperglycemia is associated with a reduced number of endothelial progenitor cells (EPCs) that impairs vascular function. Circulating EPCs play important roles in postnatal neovasculogenesis and the prevention of ischemic injury. Frequent consumption of fish oil (FO) that is abundant with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) is reportedly associated with an alleviation of diabetic complications and a lowered incidence of cardiovascular disease. The aim of this study was to examine whether N-3 polyunsaturated fatty acids such as EPA and DHA would reverse the high glucose-mediated dysfunction of EPCs in vitro and thereby prevent the ischemic injury that occurs under the hyperglycemic conditions in Type 2 diabetes (T2D) db(-/-) mice...
January 28, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28188788/angiopoietin-like-peptide-4-regulates-insulin-secretion-and-islet-morphology
#7
Hyun-Kyong Kim, Obin Kwon, Kyeong-Han Park, Kyung Jin Lee, Byung-Soo Youn, Seung-Whan Kim, Min-Seon Kim
Insulin secretion from pancreatic islet β-cells is primarily regulated by the blood glucose level, and also modulated by a number of biological factors produced inside the islets or released from remote organs. Previous studies have shown that angiopoietin-like protein 4 (Angptl4) controls glucose and lipid metabolism through its actions in the liver, adipose tissue, and skeletal muscles. In this present study, we investigated the possible role of Angptl4 in the regulation of insulin secretion from pancreatic islets...
February 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28183456/regulation-of-the-novel-adipokines-hepatokines-fetuin-a-and-fetuin-b-in-gestational-diabetes-mellitus
#8
Susan Kralisch, Annett Hoffmann, Ulrike Lössner, Jürgen Kratzsch, Matthias Blüher, Michael Stumvoll, Mathias Fasshauer, Thomas Ebert
OBJECTIVE: Fetuin B has recently been introduced as a novel adipokine/hepatokine which is significantly increased in hepatic steatosis and mediates impaired insulin action, as well as glucose intolerance. However, regulation of fetuin B in gestational diabetes mellitus (GDM), as well as its longitudinal changes in the peripartum period, have not been elucidated, so far. DESIGN AND METHODS: Circulating fetuin A and fetuin B were quantified in 74 women with GDM and 74 healthy and gestational age-matched controls by enzyme-linked immunosorbent assay during pregnancy (median gestational age: 201days)...
March 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28182694/insulin-treatment-prevents-wounding-associated-changes-in-tissue-and-circulating-neutrophil-mmp-9-and-ngal-in-diabetic-rats
#9
Maryam Abdollahi, Taria Shin Yi Ng, Alireza Rezaeizadeh, Sarah Aamidor, Stephen M Twigg, Danqing Min, Susan V McLennan
Neutrophils are important for wound repair, but their persistence can impair the healing process. Neutrophils express matrix metalloproteinases including MMP-9 and its regulator neutrophil gelatinase associated lipocalin (NGAL). Whether wounding affects neutrophil MMP-9 and NGAL in diabetic animals is not known. Skin wound tissue MMP-9 and NGAL was examined by qRT-PCR and immunohistochemistry in control, diabetic and insulin treated diabetic rats. The temporal expression of MMP-9 and NGAL mRNA, MMP-9 activity and the NGAL/MMP-9 complex was also investigated in an implant model and their circulating neutrophils...
2017: PloS One
https://www.readbyqxmd.com/read/28179377/hepcidin-links-gluco-toxicity-to-pancreatic-beta-cell-dysfunction-through-inhibiting-pdx-1-expression
#10
Xuhua Mao, Hucheng Chen, Junmin Tang, Liangliang Wang, Tingting Shu
OBJECTIVE: Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on β-cell function through impaired insulin synthesis. Although it is known that the expression and activity of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in β-cell gluco-toxicity. DESIGN: We first confirmed that high glucose levels inhibited hepcidin expression in the mouse insulinoma cell line, MIN6...
February 8, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28178568/midgut-derived-activin-regulates-glucagon-like-action-in-the-fat-body-and-glycemic-control
#11
Wei Song, Daojun Cheng, Shangyu Hong, Benoit Sappe, Yanhui Hu, Neil Wei, Changqi Zhu, Michael B O'Connor, Pavlos Pissios, Norbert Perrimon
While high-caloric diet impairs insulin response to cause hyperglycemia, whether and how counter-regulatory hormones are modulated by high-caloric diet is largely unknown. We find that enhanced response of Drosophila adipokinetic hormone (AKH, the glucagon homolog) in the fat body is essential for hyperglycemia associated with a chronic high-sugar diet. We show that the activin type I receptor Baboon (Babo) autonomously increases AKH signaling without affecting insulin signaling in the fat body via, at least, increase of Akh receptor (AkhR) expression...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28178567/defective-branched-chain-amino-acid-catabolism-disrupts-glucose-metabolism-and-sensitizes-the-heart-to-ischemia-reperfusion-injury
#12
Tao Li, Zhen Zhang, Stephen C Kolwicz, Lauren Abell, Nathan D Roe, Maengjo Kim, Bo Zhou, Yang Cao, Julia Ritterhoff, Haiwei Gu, Daniel Raftery, Haipeng Sun, Rong Tian
Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28177704/the-rab-gtpase-activating-protein-tbc1d1-is-critical-for-maintaining-normal-glucose-homeostasis-and-%C3%AE-cell-mass
#13
Sabina Paglialunga, Genevieve Simnett, Holly Robson, Monica Hoang, Renjitha Pillai, Alicia M Arkell, Jeremy A Simpson, Arend Bonen, Mark Huising, Jamie W Joseph, Graham P Holloway
TBC1D1, a Rab-GTPase activating protein, is a paralogue of AS160, and has been implicated in the canonical insulin-signaling cascade in peripheral tissues. More recently, TBC1D1 was identified in rat and human pancreatic islets, however the islet function of TBC1D1 remains not fully understood. We examined the role of TBC1D1 in glucose homeostasis and insulin secretion utilizing a rat knockout (KO) model. Chow-fed TBC1D1 KO rats had improved insulin action but impaired glucose-tolerance test (GTT) and a lower insulin response during an ipGTT compared to WT rats...
January 31, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28163317/embelin-attenuates-adipogenesis-and-lipogenesis-through-activating-canonical-wnt-signaling-and-inhibits-high-fat-diet-induced-obesity
#14
Y Gao, J Li, X Xu, S Wang, Y Yang, J Zhou, L Zhang, F Zheng, X Li, B Wang
BACKGROUND: Recent studies suggest that Embelin, a natural plant extract might have the potential to prevent body weight gain in rats. However, the mechanisms involved remain to be elucidated. METHODS: Effects of Embelin on adipocyte differentiation and lipogenesis were studied in murine ST2 stromal cells and C3H10T1/2 mesenchymal cells. The mechanisms through which Embelin regulates adipogenic differentiation and lipogenesis were explored. The in vivo anti-obesity effects of Embelin in high-fat diet (HFD)-induced obesity mice and possible transcriptional impact were investigated...
February 6, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28161274/valproate-acid-vpa-induced-dysmetabolic-function-in-clinical-and-animal-studies
#15
Rong Li, Lisheng Liang, Xinmou Wu, Xianli Ma, Min Su
BACKGROUND: Valproate acid (VPA), a commonly used antiepileptic medicine, is found to be linked to developing dysmetabolic risk. However, the proposed mechanism remains completely unknown. METHODS: In this study, we collected data from patients with epilepsy and further investigated the preclinical study in mice. RESULTS: As results, the clinical data showed that VPA-used patients resulted in higher levels of blood glucose, urine acid, triglyceride (TG), and immune cells (leucocyte, neutrophil leucocyte) when compared to clinically diagnosed references, while circulating apolipoprotein A1 (Apob A1) and fatty acid binding protein 4 (FABP4) were reduced without visible drug-induced liver injury (DILI)...
February 2, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28153729/4-pba-reverses-autophagic-dysfunction-and-improves-insulin-sensitivity-in-adipose-tissue-of-obese-mice-via-akt-mtor-signaling
#16
Qinyue Guo, Lin Xu, Huixia Li, Hongzhi Sun, Shufang Wu, Bo Zhou
BACKGROUND: 4-phenyl butyric acid (4-PBA) has been considered as a key regulator of insulin resistance in obesity. However the mechanism of 4-PBA involved in insulin resistance remains elusive. METHODS: We evaluated the effect of 4-PBA on abnormal autophagy and endoplasmic reticulum (ER) stress in obese mice. 4-PBA was administered in obese mice and adipocyte models, and metabolic parameters, autophagy markers, ER stress indicators, Akt/mTOR signaling and insulin signaling molecular were assessed...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28153708/steroidogenic-acute-regulatory-protein-star-overexpression-attenuates-hfd-induced-hepatic-steatosis-and-insulin-resistance
#17
Yanyan Qiu, Xianxian Sui, Yongkun Zhan, Chen Xu, Xiaobo Li, Yanxia Ning, Xiuling Zhi, Lianhua Yin
Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology. Intracellular lipid accumulation is the first step in the development and progression of NAFLD. Steroidogenic acute regulatory protein (StAR) plays an important role in the synthesis of bile acid and intracellular lipid homeostasis and cholesterol metabolism. We hypothesize that StAR is involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. The hypothesis was identified using free fatty acid (FFA)-overloaded NAFLD in vitro model and high-fat diet (HFD)-induced NAFLD mouse model transfected by recombinant adenovirus encoding StAR (StAR)...
January 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28145434/%C3%AE-arrestin-2-is-an-essential-regulator-of-pancreatic-%C3%AE-cell-function-under-physiological-and-pathophysiological-conditions
#18
Lu Zhu, Joana Almaça, Prasanna K Dadi, Hao Hong, Wataru Sakamoto, Mario Rossi, Regina J Lee, Nicholas C Vierra, Huiyan Lu, Yinghong Cui, Sara M McMillin, Nicole A Perry, Vsevolod V Gurevich, Amy Lee, Bryan Kuo, Richard D Leapman, Franz M Matschinsky, Nicolai M Doliba, Nikhil M Urs, Marc G Caron, David A Jacobson, Alejandro Caicedo, Jürgen Wess
β-arrestins are critical signalling molecules that regulate many fundamental physiological functions including the maintenance of euglycemia and peripheral insulin sensitivity. Here we show that inactivation of the β-arrestin-2 gene, barr2, in β-cells of adult mice greatly impairs insulin release and glucose tolerance in mice fed with a calorie-rich diet. Both glucose and KCl-induced insulin secretion and calcium responses were profoundly reduced in β-arrestin-2 (barr2) deficient β-cells. In human β-cells, barr2 knockdown abolished glucose-induced insulin secretion...
February 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28137917/elevating-cxcr7-improves-angiogenic-function-of-epcs-via-akt-gsk-3%C3%AE-fyn-mediated-nrf2-activation-in-diabetic-limb-ischemia
#19
Xiaozhen Dai, Xiaoqing Yan, Jun Zeng, Jing Chen, Yuehui Wang, Jun Chen, Yan Li, Michelle T Barati, Kupper A Wintergerst, Kejian Pan, Matthew A Nystoriak, Daniel J Conklin, Gregg Rokosh, Paul N Epstein, Xiaokun Li, Yi Tan
RATIONALE: Endothelial progenitor cells (EPCs) respond to SDF-1 through receptors CXCR7 and CXCR4. Whether SDF-1 receptors involves in diabetes induced EPCs dysfunction remains unknown. OBJECTIVE: To determine the role of SDF-1 receptors in diabetic EPCs dysfunction. METHODS AND RESULTS: CXCR7 expression, but not CXCR4 was reduced in EPCs from db/db mice, which coincided with impaired tube formation. Knockdown of CXCR7 impaired tube formation of EPCs from normal mice, while up-regulation of CXCR7 rescued angiogenic function of EPCs from db/db mice...
January 30, 2017: Circulation Research
https://www.readbyqxmd.com/read/28137631/a-single-non-synonymous-ncoa5-variation-in-type-2-diabetic-patients-with-hepatocellular-carcinoma-impairs-the-function-of-ncoa5-in-cell-cycle-regulation
#20
Xinhui Liu, Feiye Liu, Shenglan Gao, Jake Reske, Aimin Li, Chin-Lee Wu, Chengfeng Yang, Fengsheng Chen, Rongcheng Luo, Hua Xiao
Type 2 Diabetes (T2D) is a risk factor for hepatocellular carcinoma (HCC). We have previously described that haploinsufficiency of nuclear receptor coactivator 5 (NCOA5) is a genetic defect linking glucose intolerance to HCC. Here we report identification and characterization of a single nucleotide variation (T445A) in NCOA5, causing an amino acid Thr to Ala substitution, in adjacent non-tumorous liver tissues derived from patients with concurrent HCC and T2D. By using Tet-On inducible expression cells, we show that ectopic expression of NCOA5wt suppressed proliferation of HCC cells via induction of G2/M arrest, while ectopic expression of NCOA5T445A had a significantly lesser effect compared to ectopic expression of NCOA5wt...
January 27, 2017: Cancer Letters
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