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Insulin & Weight Gain

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https://www.readbyqxmd.com/read/28107465/lead-exposure-induces-weight-gain-in-adult-rats-accompanied-by-dna-hypermethylation
#1
Honglin Sun, Ningjian Wang, Xiaomin Nie, Li Zhao, Qin Li, Zhen Cang, Chi Chen, Meng Lu, Jing Cheng, Hualing Zhai, Fangzhen Xia, Lin Ye, Yingli Lu
OBJECTIVE: Previous studies have revealed the association of lead (Pb) exposure with obesity. DNA methylation alteration has been suggested to be one of the regulatory mechanisms of obesity. We aimed to explore whether Pb exposure is related with weight gain and DNA methylation alteration. METHODS: Male adult 8 week Wistar rats were divided into 5 groups: the normal chow diet (NCD); the NCD+0.05%Pb; the NCD+0.15%Pb; the NCD+0.45%Pb and the high fat diet. Rats were exposed to different dosages of Pb through drinking water for 21 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28105735/observational-registry-of-basal-insulin-treatment-orbit-in-patients-with-type-2-diabetes-uncontrolled-with-oral-antihyperglycaemic-drugs-real-life-use-of-basal-insulin-in-china
#2
Linong Ji, Puhong Zhang, Dongshan Zhu, Xian Li, Jiachao Ji, Juming Lu, Xiaohui Guo, Weiping Jia, Jianping Weng, Yangfeng Wu, Wenying Yang, Dajin Zou, Zhiguang Zhou, Changyu Pan, Yan Gao, Satish K Garg
AIMS: To examine treatment patterns following basal insulin (BI) introduction in type 2 diabetes mellitus (T2DM) patients under real-world conditions across China. MATERIALS AND METHODS: Overall, 18,995 patients inadequately controlled [HbA1c ≥ 53 mmol/mol (7%)] with oral antihyperglycaemic drugs (OADs) and willing to receive BI treatment were registered at 209 hospitals and followed at baseline (visit 1), 3 months (visit 2), and 6 months (visit 3). Type of BI was initiated at physicians' discretion...
January 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28105274/design-synthesis-and-evaluation-of-novel-and-selective-g-protein-coupled-receptor-120-gpr120-spirocyclic-agonists
#3
Jason M Cox, Hong D Chu, Mariappan V Chelliah, John S Debenham, Keith Eagen, Ping Lan, Matthew Lombardo, Clare London, Michael A Plotkin, Unmesh Shah, Zhongxiang Sun, Henry M Vaccaro, Srikanth Venkatraman, Takao Suzuki, Nengxue Wang, Eric R Ashley, Alejandro Crespo, Maria Madeira, Dennis H Leung, Candice Alleyne, Aimie M Ogawa, Sarah Souza, Brande Thomas-Fowlkes, Jerry Di Salvo, Adam Weinglass, Melissa Kirkland, Michele Pachanski, Mary Ann Powles, Effie Tozzo, Taro E Akiyama, Feroze Ujjainwalla, James R Tata, Christopher J Sinz
Type 2 diabetes mellitus (T2DM) is an ever increasing worldwide epidemic, and the identification of safe and effective insulin sensitizers, absent of weight gain, has been a long-standing goal of diabetes research. G-protein coupled receptor 120 (GPR120) has recently emerged as a potential therapeutic target for treating T2DM. Natural occurring, and more recently, synthetic agonists have been associated with insulin sensitizing, anti-inflammatory, and fat metabolism effects. Herein we describe the design, synthesis, and evaluation of a novel spirocyclic GPR120 agonist series, which culminated in the discovery of potent and selective agonist 14...
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28104917/overexpression-of-bone-morphogenetic-protein-3b-bmp-3b-in-adipose-tissues-protects-against-high-fat-diet-induced-obesity
#4
J Hino, M Nakatani, Y Arai, K Tsuchida, M Shirai, M Miyazato, K Kangawa
BACKGROUND: Bone morphogenetic protein-3b (BMP-3b) is a member of the transforming growth factor-β superfamily and has several activities that differ from those of other BMPs. We previously found that BMP-3b is highly expressed in adipocytes, its level is increased during obesity, and it inhibits adipogenesis by suppressing peroxisome proliferator-activated receptor γ (PPARγ) in vitro. However, the function of BMP-3b in adipose tissues in vivo remains unknown. METHODS: To determine the role of BMP-3b overexpression in adipose tissues in vivo, we generated transgenic mice (BMP-3b Tg) by using a conditional overexpression approach in fatty acid binding protein 4 (FABP4)-expressing adipocytes...
January 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28101792/medical-management-of-diabesity-do-we-have-realistic-targets
#5
REVIEW
Joseph M Pappachan, Ananth K Viswanath
PURPOSE OF REVIEW: The global prevalence of "diabesity"-diabetes related to obesity-is increasing steadily over the past few decades because of the obesity epidemic. Although bariatric surgery is an effective treatment option for patients with diabesity, its limited availability, invasiveness, relatively high costs and the potential for surgical and postsurgical complications restrict its widespread use. Therefore, medical management is the only option for a majority of patients with diabesity...
January 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28098516/germacrone-attenuates-hyperlipidemia-and-improves-lipid-metabolism-in-high-fat-diet-induced-obese-c57bl-6j-mice
#6
Yuan-Ri Guo, Se-Young Choung
We previously showed that Aster spathulifolius Maxim extract (ASE) reduced body weight gain and serum and liver lipid levels and significantly suppressed serum insulin and leptin concentrations in high-fat diet (HFD)-induced obese rats. Germacrone (GM) was identified as a potent bioactive constituent of ASE. In this study, we hypothesized that GM can attenuate hyperlipidemia by alleviating fatty acid (FA) synthesis/uptake and improve lipid metabolism by stimulating FA β-oxidation in HFD-induced obese C57BL/6J mice...
January 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28096223/combination-therapy-with-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-poorly-controlled-patients-with-type-2-diabetes-on-sulfonylurea-plus-metformin-the-qatar-study
#7
Muhammad Abdul-Ghani, Osama Migahid, Ayman Megahed, John Adams, Curtis Triplitt, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
OBJECTIVE: The Qatar Study was designed to examine the efficacy of combination therapy with exenatide plus pioglitazone versus basal-bolus insulin in patients with long-standing poorly controlled type 2 diabetes mellitus (T2DM) on metformin plus a sulfonylurea. RESEARCH DESIGN AND METHODS: The study randomized 231 patients with poorly controlled (HbA1c >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive 1) pioglitazone plus weekly exenatide (combination therapy), or 2) basal plus prandial insulin (insulin therapy) to maintain HbA1c <7...
January 17, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28092788/patient-level-meta-analysis-of-efficacy-and-hypoglycaemia-in-people-with-type-2-diabetes-initiating-insulin-glargine-100u-ml-or-neutral-protamine-hagedorn-insulin-analysed-according-to-concomitant-oral-antidiabetes-therapy
#8
David R Owens, Louise Traylor, Peter Mullins, Wolfgang Landgraf
AIMS: Evaluate efficacy and hypoglycaemia according to concomitant oral antidiabetes drug (OAD) in people with type 2 diabetes initiating insulin glargine 100U/mL (Gla-100) or neutral protamine Hagedorn (NPH) insulin once daily. METHODS: Four studies (target fasting plasma glucose [FPG] ⩽100mg/dL [⩽5.6mmol/L]; duration ⩾24weeks) were included. Standardised data from 2091 subjects (Gla-100, n=1024; NPH insulin, n=1067) were analysed. Endpoints included glycated haemoglobin (HbA1c) and FPG change, glycaemic target achievement, hypoglycaemia, weight change, and insulin dose...
November 9, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28089867/attenuation-of-obesity-induced-inflammation-in-mice-orally-administered-with-salmon-cartilage-proteoglycan-a-prophylactic-agent
#9
Shouhei Hirose, Krisana Asano, Akio Nakane
Obesity is associated with chronic inflammation of adipose tissue and causes development of type 2 diabetes. M1 macrophage population was increased in adipose tissue of obese mouse. M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines. Our previous studies demonstrated that salmon cartilage proteoglycan (PG) suppresses excess inflammation in various mouse inflammatory diseases. In this study, we examined the effect of PG on type 2 diabetes using high-fat-diet (HFD) induced obese mouse model...
January 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#10
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28077863/what-have-human-experimental-overfeeding-studies-taught-us-about-adipose-tissue-expansion-and-susceptibility-to-obesity-and-metabolic-complications
#11
REVIEW
D J Cuthbertson, T Steele, J P Wilding, J C G Halford, J A Harrold, M Hamer, F Karpe
Overfeeding experiments, in which we impose short-term positive energy balance, help unravel the cellular, physiological and behavioural adaptations to nutrient excess. These studies mimic longer-term mismatched energy expenditure and intake. There is considerable inter-individual heterogeneity in the magnitude of weight gain when exposed to similar relative caloric excess reflecting variable activation of compensatory adaptive mechanisms. Significantly, given similar relative weight gain, individuals may be protected from/predisposed to metabolic complications (insulin resistance, dyslipidaemia, hypertension), non-alcoholic fatty liver disease and cardiovascular disease...
January 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28077576/specific-inhibition-of-acyl-coa-oxidase-1-by-an-acetylenic-acid-improves-hepatic-lipid-and-reactive-oxygen-species-ros-metabolism-in-rats-fed-a-high-fat-diet
#12
Jia Zeng, Senwen Deng, Yiping Wang, Ping Li, Lian Tang, Yefeng Pang
Chronic high-fat diet (HFD) results in hepatic mitochondrial dysfunction and induction of peroxisomal fatty acid oxidation (FAO), whether specific inhibition of peroxisomal FAO benefits mitochondrial FAO and reactive oxygen species (ROS) metabolism remains unclear. In this study, a specific inhibitor for the rate-limiting enzyme involved in peroxisomal FAO, acyl-CoA oxidase-1 (ACOX1) was developed and used for the investigation of peroxisomal FAO inhibition upon mitochondrial FAO and ROS metabolism. Specific inhibition of ACOX1 by 10,12 -tricosadiynoic acid increased hepatic mitochondrial FAO via activation of the SIRT1-AMPK pathway and PPARα and reduced hydrogen peroxide accumulation in high-fat diet fed rats, which significantly decreased hepatic lipid and ROS contents, reduced body weight gain and decreased serum triglyceride and insulin levels...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28076453/ferulic-acid-lowers-body-weight-and-visceral-fat-accumulation-via-modulation-of-enzymatic-hormonal-and-inflammatory-changes-in-a-mouse-model-of-high-fat-diet-induced-obesity
#13
T S de Melo, P R Lima, K M M B Carvalho, T M Fontenele, F R N Solon, A R Tomé, T L G de Lemos, S G da Cruz Fonseca, F A Santos, V S Rao, M G R de Queiroz
Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20-25 g (n=6-8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed...
January 5, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28073831/deletion-of-protein-kinase-c-lambda-in-pomc-neurons-predisposes-to-diet-induced-obesity
#14
Mauricio D Dorfman, Jordan E Krull, Jarrad M Scarlett, Stephan J Guyenet, Mini P Sajan, Vincent Damian, Hong T Nguyen, Michael Leitges, Gregory J Morton, Robert V Farese, Michael W Schwartz, Joshua P Thaler
Effectors of the phosphoinositide 3-kinase (PI3K) signal transduction pathway contribute to the hypothalamic regulation of energy and glucose homeostasis in divergent ways. Here we show that CNS action of the PI3K signaling intermediate atypical protein kinase C (aPKC) constrains food intake, weight gain, and glucose intolerance in both rats and mice. Pharmacologic inhibition of CNS aPKC activity acutely increases food intake and worsens glucose tolerance in chow-fed rodents and causes excess weight gain during high fat diet (HFD) feeding...
January 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28068899/maternal-bmi-as-a-predictor-of-methylation-of-obesity-related-genes-in-saliva-samples-from-preschool-age-hispanic-children-at-risk-for-obesity
#15
Kathryn Tully Oelsner, Yan Guo, Sophie Bao-Chieu To, Amy L Non, Shari L Barkin
BACKGROUND: The study of epigenetic processes and mechanisms present a dynamic approach to assess complex individual variation in obesity susceptibility. However, few studies have examined epigenetic patterns in preschool-age children at-risk for obesity despite the relevance of this developmental stage to trajectories of weight gain. We hypothesized that salivary DNA methylation patterns of key obesogenic genes in Hispanic children would 1) correlate with maternal BMI and 2) allow for identification of pathways associated with children at-risk for obesity...
January 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28068222/long-term-administration-of-nicotinamide-mononucleotide-mitigates-age-associated-physiological-decline-in-mice
#16
Kathryn F Mills, Shohei Yoshida, Liana R Stein, Alessia Grozio, Shunsuke Kubota, Yo Sasaki, Philip Redpath, Marie E Migaud, Rajendra S Apte, Koji Uchida, Jun Yoshino, Shin-Ichiro Imai
NAD(+) availability decreases with age and in certain disease conditions. Nicotinamide mononucleotide (NMN), a key NAD(+) intermediate, has been shown to enhance NAD(+) biosynthesis and ameliorate various pathologies in mouse disease models. In this study, we conducted a 12-month-long NMN administration to regular chow-fed wild-type C57BL/6N mice during their normal aging. Orally administered NMN was quickly utilized to synthesize NAD(+) in tissues. Remarkably, NMN effectively mitigates age-associated physiological decline in mice...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28063135/cost-effectiveness-of-insulin-degludec-plus-liraglutide-ideglira-in-a-fixed-combination-for-uncontrolled-type-2-diabetes-mellitus-in-sweden
#17
Åsa Ericsson, Adam Lundqvist
BACKGROUND: Patients with uncontrolled type 2 diabetes mellitus (T2DM) are a priority group for intensified therapy without weight gain and with low risk of hypoglycaemia. OBJECTIVE: This study evaluates the cost effectiveness of insulin degludec plus liraglutide (IDegLira, Xultophy(®)) compared with six potential intensification treatment options for patients with T2DM that is uncontrolled with basal insulin. METHODS: The Swedish Institute for Health Economics (IHE) Cohort Model of Type 2 Diabetes was used with Swedish input data, a 40-year time frame and a societal perspective...
January 6, 2017: Applied Health Economics and Health Policy
https://www.readbyqxmd.com/read/28062546/the-clinical-importance-of-quantifying-fat-distribution-during-androgen-deprivation
#18
Stephen John Foulkes, Robin M Daly, Steve Fraser
Androgen deprivation therapy (ADT) is now considered a mainstay in the treatment of metastatic and locally advanced prostate cancer (PCa). Despite well-established benefits of ADT in relation to overall survival, this treatment has been associated with a number of adverse effects, particularly with regard to key cardiometabolic risk factors including the development of insulin resistance, dyslipidaemia and increases in total and regional fat mass. In non-ADT populations, increased levels of visceral adipose tissue (VAT) are thought to be a key mediator of the increased cardiometabolic risk associated with weight gain, but this has received limited attention in men treated with ADT...
January 6, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28060600/influence-of-energy-balance-and-glycemic-index-on-metabolic-endotoxemia-in-healthy-men
#19
Nicolle Breusing, Merit Lagerpusch, Anna Janina Engstler, Ina Bergheim, Manfred J Mueller, Anja Bosy-Westphal
OBJECTIVE: Overfeeding with a high-fat and/or high-carbohydrate (CHO) diet is known to increase plasma concentrations of endotoxin (lipopolysaccharide [LPS]) that may lead to metabolic disturbances like insulin resistance. The impact of CHO quality (i.e., the glycemic index [GI]) independent of fat intake on metabolic endotoxemia remains unclear. In the present study, the effects of changes in energy balance and GI on plasma endotoxin were studied. METHODS: Fifteen healthy young men overconsumed diets containing 65% CHO and 20% fat for 1 week (OF; +50% of energy requirement) followed by 3 weeks of caloric restriction (CR; -50% of energy requirement) and were then randomized to 2 weeks hypercaloric refeeding (RF, +50% of energy requirement) with either a low- or high-GI (40 vs 74) diet...
January 6, 2017: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/28057658/pioglitazone-and-cardiovascular-outcomes-in-patients-with-insulin-resistance-pre-diabetes-and-type-2-diabetes-a-systematic-review-and-meta-analysis
#20
Hung-Wei Liao, Jeffrey L Saver, Yi-Ling Wu, Tso-Hsiao Chen, Meng Lee, Bruce Ovbiagele
OBJECTIVES: To evaluate the effect of pioglitazone in people with insulin resistance, pre-diabetes and type 2 diabetes. DESIGN AND SETTING: Systematic review and meta-analysis of randomised, controlled trials. DATA SOURCES: Literature searches were performed across PubMed, EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials from 1966 to May 2016 to identify randomised, controlled trials with more than 1 year follow-up. OUTCOME MEASURES: Relative risk (RR) with 95% CI was used to evaluate the association between pioglitazone and the risk of major adverse cardiovascular events (MACE: composite of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and safety outcomes, after pooling data across trials in a fixed-effects model...
January 5, 2017: BMJ Open
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