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Metabolism: Clinical and Experimental

Naoyuki Kitao, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Kiyohiko Takahashi, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
OBJECTIVE: We investigated whether glucokinase and insulin receptor substrate-2 were required for beta cell proliferation induced by short-term high-fat (HF) diet feeding, as has been shown for long-term HF diet. METHODS: Eight-week-old C57BL/6 J mice were exposed to either a standard chow (SC) or HF diet. After 1 week on the diet, histopathological beta cell proliferation and gene expression in isolated islets were examined. Additionally, 8-week-old beta cell-specific glucokinase haploinsufficient (Gck+/- ) and Irs2 knockout (Irs2-/- ) mice were exposed to either an SC or HF diet...
March 12, 2018: Metabolism: Clinical and Experimental
Glaucia Carneiro, Maria T Zanella
OBJECTIVE: To analyze metabolic and hormonal disorders resulting from the association between obesity and obstructive sleep apnea (OSA) syndrome that predispose to cardiovascular diseases and investigate the clinical benefits obtained from treatment approaches for both conditions. METHODS: A literature review between 1997 and 2017 was conducted in the PubMed search database. RESULTS: Obesity is the most important risk factor for OSA, and the progressive increase in its prevalence also affects OSA incidence...
March 10, 2018: Metabolism: Clinical and Experimental
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
Yeon Young Cho, Sung-Il Cho
AIMS: We explored the risks associated with metformin plus sulfonylurea (MET+SU) or MET plus a dipeptidyl peptidase-4 inhibitor (MET+DPP4i) for hypoglycemia, cardiovascular disease (CVD) events and all-cause mortality in type 2 diabetes (T2D) patients with comorbidities. METHODS: This retrospective cohort study is based on the South Korean National Health Insurance Service-National Sample Cohort, enrolling T2D patients with one or more diabetes-related comorbidities who switched from monotherapy to MET+SU or MET+DPP4i between July 1, 2008 and December 31, 2013...
March 9, 2018: Metabolism: Clinical and Experimental
Christos P Tsametis, Andrea M Isidori
The finding of low circulating testosterone level in men is relatively frequent. The symptoms of hypogonadism are very frequent in the aging men. However, the diagnosis of hypogonadism is often neglected and the opportunity to replace low testosterone in older men is highly debated. The aim of this narrative review is to summarize the steps necessary to formulate a proper diagnosis and to guide toward an individualized treatment. While universally recognized the need to treat the young adults with known causes of pituitary or testicular failure, there are controversies on the cost-benefit of treating testosterone deficiency in older men...
March 9, 2018: Metabolism: Clinical and Experimental
Xu Chen, Xuan Li, Wenyan Zhang, Jie He, Bo Xu, Bin Lei, Zhenhua Wang, Courtney Cates, Thomas Rousselle, Ji Li
BACKGROUND: AMP-activated Protein Kinase (AMPK) is a stress-activated kinase that protects against cardiomyocyte injury during ischemia and reperfusion. c-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated by ischemia and reperfusion. NF-κB is an important transcription factor involved in ischemia and reperfusion injury. METHODS AND RESULTS: The intrinsic activation of AMPK attenuates the inflammation which occurred during ischemia/reperfusion through the modulation of the JNK mediated NF-κB signaling pathway...
March 8, 2018: Metabolism: Clinical and Experimental
Susann Weihrauch-Blüher, Matthias Richter, Martin S Staege
Obesity is a complex disease which has reached epidemic dimensions. Thus, prevention of excessive weight gain and associated metabolic and cardiovascular diseases has to start as early in life as possible. The impact of epigenetic mechanisms on the regulation of genes involved in obesity is increasingly recognized. On the other hand, it is well known that socioeconomic factors influence the risk for obesity. These factors can also have an impact on epigenetic gene regulation. There is increasing body of evidence that several factors and interventions addressing extragenetic causes of obesity may not only improve individual health, but also the health of future generations by epigenetic alterations...
March 8, 2018: Metabolism: Clinical and Experimental
Gaia Botteri, Laia Salvadó, Anna Gumà, D Lee Hamilton, Paul J Meakin, Gemma Montagut, Michael L J Ashford, Victoria Ceperuelo-Mallafré, Sonia Fernández-Veledo, Joan Vendrell, María Calderón-Dominguez, Dolors Serra, Laura Herrero, Javier Pizarro, Emma Barroso, Xavier Palomer, Manuel Vázquez-Carrera
OBJECTIVE: β-secretase/β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a key enzyme involved in Alzheimer's disease that has recently been implicated in insulin-independent glucose uptake in myotubes. However, it is presently unknown whether BACE1 and the product of its activity, soluble APPβ (sAPPβ), contribute to lipid-induced inflammation and insulin resistance in skeletal muscle cells. MATERIALS/METHODS: Studies were conducted in mouse C2C12 myotubes, skeletal muscle from Bace1-/- mice and mice treated with sAPPβ and adipose tissue and plasma from obese and type 2 diabetic patients...
March 8, 2018: Metabolism: Clinical and Experimental
Zhao Dong, Haozhe Shi, Mingming Zhao, Xin Zhang, Wei Huang, Yuhui Wang, Lemin Zheng, Xunde Xian, George Liu
OBJECTIVE: Lecithin cholesterol acyltransferase (LCAT) plays a pivotal role in HDL metabolism but its influence on atherosclerosis remains controversial for decades both in animal and clinical studies. Because lack of cholesteryl ester transfer protein (CETP) is a major difference between murine and humans in lipoprotein metabolism, we aimed to create a novel Syrian Golden hamster model deficient in LCAT activity, which expresses endogenous CETP, to explore its metabolic features and particularly the influence of LCAT on the development of atherosclerosis...
March 8, 2018: Metabolism: Clinical and Experimental
Sujith Rajan, Sabbu Satish, Kripa Shankar, Sukanya Pandeti, Salil Varshney, Ankita Srivastava, Durgesh Kumar, Abhishek Gupta, Sanchita Gupta, Rakhi Choudhary, Vishal M Balaramnavar, Tadigoppula Narender, Anil N Gaikwad
BACKGROUND AND PURPOSE: In our drug discovery program of natural product, earlier we have reported Aegeline that is N-acylated-1-amino-2- alcohol, which was isolated from the leaves of Aeglemarmelos showed anti-hyperlipidemic activity for which the QSAR studies predicted the compound to be the β3-AR agonist, but the mechanism of its action was not elucidated. In our present study, we have evaluated the β3-AR activity of novel N-acyl-1-amino-3-arylopropanol synthetic mimics of aegeline and its beneficial effect in insulin resistance...
March 7, 2018: Metabolism: Clinical and Experimental
Marc A Tuazon, Sara C Campbell, Dylan J Klein, Sue A Shapses, Keith R Anacker, Tracy G Anthony, Mehmet Uzumcu, Gregory C Henderson
BACKGROUND: Menopause is associated with fatty liver, glucose dysregulation, increased body fat, and impaired bone quality. Previously, it was demonstrated that single sessions of high-intensity interval exercise (HIIE) are more effective than distance- and duration-matched continuous exercise (CE) on altering hepatic triglyceride (TG) metabolism and very-low density lipoprotein-TG (VLDL-TG) secretion. METHODS: Six weeks training using these modalities was examined for effects on hepatic TG metabolism/secretion, glucose tolerance, body composition, and bone mineral density (BMD) in ovariectomized (OVX) and sham-operated (SHAM) mice...
March 6, 2018: Metabolism: Clinical and Experimental
Ewelina K Wardzinski, Alina Kistenmacher, Uwe H Melchert, Kamila Jauch-Chara, Kerstin M Oltmanns
BACKGROUND: There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. METHODS: Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L...
March 6, 2018: Metabolism: Clinical and Experimental
Huina Zhang, Fan Yang, Yichen Guo, Li Wang, Fang Fang, Hao Wu, Shaoping Nie, Yifan Wang, Man-Lung Fung, Yu Huang, Haiteng Deng, Yanwen Qin, Xinliang Ma, Yongxiang Wei
OBJECTIVE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is an independent risk factor for many clinical complications. However, how OSAHS cause multiple organ injury and initiate inter-organ communication remains unclear. Moreover, despite it is well-recognized that chronic intermittent hypoxia (CIH) is a main feature of OSAHS, specific contribution of CIH to overall OSAHS-initiated pathological complications remains unclear. This study aimed to use an unbiased proteomic approach to determine whether OSAHS alters protein profiles of serum extracellular microvesicles (SEMVs) and how CIH contributes to such alterations...
March 6, 2018: Metabolism: Clinical and Experimental
Spatola Leonardo, Ferraro Manuel Pietro, Gambaro Giovanni, Badalamenti Salvatore, Dauriz Marco
Uric acid nephrolithiasis (UAN) is an increasingly common disease in ethnically diverse populations and constitutes about 10% of all kidney stones. Metabolic syndrome and diabetes mellitus are accounted amongst the major risk factors for UAN, together with environmental exposure, individual lifestyle habits and genetic predisposition. The development and overt manifestation of UAN appears to stem on the background of insulin resistance, which acts at the kidney level by reducing urinary pH, thus hampering the ability of the kidney to generate renal ammonium in response to an acid load...
March 3, 2018: Metabolism: Clinical and Experimental
Sirimon Reutrakul, Eve Van Cauter
A large body of epidemiologic evidence has linked insufficient sleep duration and quality to the risk of obesity, insulin resistance and type 2 diabetes. To address putative causal mechanisms, this review focuses on laboratory interventions involving several nights of experimental sleep restriction, fragmentation or extension and examining metabolically relevant outcomes. Sleep restriction has been consistently shown to increase hunger, appetite and food intake, with the increase in caloric intake in excess of the energy requirements of extended wakefulness...
March 3, 2018: Metabolism: Clinical and Experimental
Hiroko Hashimoto, Naohiro Nomura, Wakana Shoda, Kiyoshi Isobe, Hiroaki Kikuchi, Kouhei Yamamoto, Takuya Fujimaru, Fumiaki Ando, Takayasu Mori, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
OBJECTIVE: Metformin is an antidiabetic drug that is widely used to treat patients with diabetes mellitus. Recent studies have reported that treatment with metformin not only improved blood glucose levels but also reduced blood pressure. However, it remains unclear how metformin reduces blood pressure. We hypothesized that metformin affects sodium reabsorption in the kidneys. METHODS: Urinary sodium excretion and expression of renal sodium transporters were examined in 8-week-old male C57BL/6 mice with acute and chronic treatment of metformin...
March 3, 2018: Metabolism: Clinical and Experimental
Alessandro Mantovani, Giovanni Targher, Pier Luigi Temporelli, Donata Lucci, Lucio Gonzini, Gian Luigi Nicolosi, Roberto Marchioli, Gianni Tognoni, Roberto Latini, Franco Cosmi, Luigi Tavazzi, Aldo Pietro Maggioni
BACKGROUND: The prognostic impact of hyperuricemia on long-term clinical outcomes in patients with chronic heart failure (HF) has been investigated in observational registries and clinical trials, but the results have been often inconclusive. We examined the prognostic impact of elevated serum uric acid levels on long-term clinical outcomes in the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial. METHODS: We assessed the rates of all-cause death, cardiovascular death, cardiovascular hospitalization and the composite of all-cause death or cardiovascular hospitalization over a median follow-up of 3...
February 22, 2018: Metabolism: Clinical and Experimental
Marta Montori-Grau, Robert Pedreira-Casahuga, Zoé Boyer-Díaz, Iréna Lassot, Celia García-Martínez, Anna Orozco, Judith Cebrià, Oscar Osorio-Conles, Matilde R Chacón, Joan Vendrell, Manuel Vázquez-Carrera, Solange Desagher, Josep Carles Jiménez-Chillarón, Anna Ma Gómez-Foix
BACKGROUND: Glycogenin-interacting protein 1 (GNIP1) is a tripartite motif (TRIM) protein with E3 ubiquitin ligase activity that interacts with glycogenin. These data suggest that GNIP1 could play a major role in the control of glycogen metabolism. However, direct evidence based on functional analysis remains to be obtained. OBJECTIVES: The aim of this study was 1) to define the expression pattern of glycogenin-interacting protein/Tripartite motif containing protein 7 (GNIP/TRIM7) isoforms in humans, 2) to test their ubiquitin E3 ligase activity, and 3) to analyze the functional effects of GNIP1 on muscle glucose/glycogen metabolism both in human cultured cells and in vivo in mice...
February 18, 2018: Metabolism: Clinical and Experimental
Sun Ryoung Choi, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Yaeni Kim, Beom Soon Choi, Yong-Soo Kim, Hye Won Kim, Kyung-Min Lim, Min Jeong Kim, Cheol Whee Park
BACKGROUND: Adiponectin is known to take part in the regulation of energy metabolism. AdipoRon, an orally-active synthetic adiponectin agonist, binds to both adiponectin receptors (AdipoR)1/R2 and ameliorates diabetic complications. Among the lipid metabolites, the ceramide subspecies of sphingolipids have been linked to features of lipotoxicity, including inflammation, cell death, and insulin resistance. We investigated the role of AdipoRon in the prevention and development of type 2 diabetic nephropathy...
February 17, 2018: Metabolism: Clinical and Experimental
Bigina N R Ginos, Sandi L Navarro, Yvonne Schwarz, Haiwei Gu, Dongfang Wang, Timothy W Randolph, Ali Shojaie, Meredith A J Hullar, Paul D Lampe, Mario Kratz, Marian L Neuhouser, Daniel Raftery, Johanna W Lampe
OBJECTIVE: The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively. However, the effects of diets high in whole versus refined grains on circulating bile acids, which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied. MATERIALS AND METHODS: We conducted a secondary analysis from a randomized controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40 women/40 men, age 18-45 years) from the greater Seattle Area, half of which were normal weight (BMI 18...
February 16, 2018: Metabolism: Clinical and Experimental
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