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American Journal of Physiology. Endocrinology and Metabolism

Yan Jin, Hana Vakili, SongYan Liu, Savas Menticoglou, Margaret E Bock, Peter A Cattini
The human (h) placental lactogenic hormone chorionic somatomammotropin (CS) is highly produced during pregnancy and acts as a metabolic adaptor in response to maternal insulin resistance. Maternal obesity can exacerbate this "resistance" and a >75% decrease in CS RNA levels was observed in term placentas from obese versus lean women. The genes coding for hCS (hCS-A and hCS-B) and placental growth hormone (hGH-V) as well as the hCS-L pseudogene and pituitary growth hormone (GH) gene (hGH-N) are located at a single locus on chromosome 17...
May 15, 2018: American Journal of Physiology. Endocrinology and Metabolism
Greta Trogen, Joshua Bacon, Ying Li, Gary L Wright, Ashley Degroat, Kendra L Hagood, Zachary Warren, Allan Forsman, Aruna Kilaru, W Andrew Clark, Jonathan M Peterson
This study tested the ability of a novel adipose tissue derived cytokine, C1q TNF Related Protein 3 (CTRP3), to prevent alcohol-induced hepatic lipid accumulation, or alcoholic fatty liver disease (ALD). Previous work has demonstrated that CTRP3 is effective at preventing high fat diet-induced fatty liver, however, the potential of CTRP3 to inhibit ALD has not been explored. To test the potential protective effects of CTRP3, transgenic mice overexpressing CTRP3 (Tg) or wildtype littermates (WT) were subjected to one of two different models of ALD...
May 15, 2018: American Journal of Physiology. Endocrinology and Metabolism
Ryan D Russell, Donghua Hu, Timothy Greenaway, James E Sharman, Stephen Rattigan, Stephen M Richards, Michelle A Keske
Skeletal muscle microvascular (capillary) blood flow increases in the post-prandial state or during insulin infusion due to dilation of pre-capillary arterioles to augment glucose disposal. This effect occurs independent of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict pre-capillary arterioles, and causes muscle insulin resistance in vivo. We hypothesize that acute hyperglycemia impairs post-prandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans...
May 15, 2018: American Journal of Physiology. Endocrinology and Metabolism
Tongxin Wang, Weilei Yao, Ji Li, Qiongyu He, Yafei Shao, Feiruo Huang
Hepatic metabolic syndrome is associated with inflammation, as it stimulates the reprogramming of nutrient metabolism and hepatic mitochondria-generated acetyl-CoA. But how acetyl-CoA affects the reprogramming of nutrient metabolism, especially glucose and fatty acids, in the condition of inflammation is still unclear. Here, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS), and found that hepatic glycolysis and fatty acid oxidation are both promoted. Acetyl-proteome profiling of LPS-infected pigs liver showed that inflammatory stress exacerbates the acetylation of mitochondrial proteins...
May 15, 2018: American Journal of Physiology. Endocrinology and Metabolism
Carolina Nylén, Wataru Aoi, Ahmed M Abdelmoez, David G Lassiter, Leonidas S Lundell, Harriet Wallberg-Henriksson, Erik Näslund, Nicolas J Pillon, Anna Krook
AMPK controls glucose- and lipid- metabolism and modulates inflammatory responses to maintain metabolic and inflammatory homeostasis during low cellular energy levels. The AMPK activator 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) interferes with inflammatory pathways in skeletal muscle, but the mechanisms are undefined. We hypothesized that AMPK activation reduces cytokine mRNA levels by blocking transcription through one or several transcription factors. Three skeletal muscle models were used to study AMPK effects on cytokine mRNA: human skeletal muscle strips obtained from healthy men incubated in vitro, primary human muscle cells and rat L6 cells...
April 24, 2018: American Journal of Physiology. Endocrinology and Metabolism
Junlong Wang, Shimeng Xu, Jing Gao, Linqiang Zhang, Zhiguo Zhang, Wenhui Yang, Yunhai Li, Shasha Liao, Hu Zhou, Pingsheng Liu, Bin Liang
Type 2 diabetes mellitus (T2DM) is a severely metabolic disorder that affects above 10% worldwide population. Obesity is a major cause of insulin resistance and contributes to the development of T2DM. Liver is an essential metabolic organ that plays crucial roles in the pathogenesis of obesity and diabetes. However, the underlying mechanisms of liver in the transition of obesity to diabetes are not fully understood. Nonhuman primate (NHP) rhesus monkey is an appropriate animal for research of human diseases...
April 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
R J Allen, Cynthia J Musante
Fructose is a major component of Western diets and is implicated in the pathogenesis of obesity and type 2 diabetes. In response to an oral challenge, the majority of fructose is cleared during "first-pass" liver metabolism, primarily via phosphorylation by ketohexokinase (KHK). A rare benign genetic deficiency in KHK, called essential fructosuria (EF), leads to altered fructose metabolism. The only reported symptom of EF is the appearance of fructose in the urine following either oral or intravenous fructose administration...
April 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Frances L Byrne, Ellen M Olzomer, Robert Brink, Kyle L Hoehn
Glucose transporter 6 (GLUT6) is a member of the facilitative glucose transporter family. GLUT6 is up-regulated in several cancers, but is not widely expressed in normal tissues. Previous studies have shown that GLUT6 knockdown kills endometrial cancer cells that express elevated levels of the protein. However, whether GLUT6 represents a viable anti-cancer drug target is unclear because the role of GLUT6 in normal metabolic physiology is unknown. Herein we generated GLUT6 knockout mice to determine how loss of GLUT6 affected whole body glucose homeostasis and metabolic physiology...
April 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Candice Allister Price, Donovan A Argueta, Valentina Medici, Andrew A Bremer, Vivien Lee, Marinelle V Nunez, Guoxia X Chen, Nancy L Keim, Peter J Havel, Kimber L Stanhope, Nicholas V DiPatrizio
Epidemiological and clinical research studies have provided ample evidence demonstrating that consumption of sugar-sweetened beverages (SSB) increases risk factors involved in the development of obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD). Our previous study demonstrated that when compared to aspartame (Asp), two weeks of high-fructose corn syrup (HFCS)-sweetened beverages provided at 25% of daily energy requirement (Ereq) was associated with increased body weight, postprandial (pp) triglycerides (TG), and fasting and pp CVD risk factors in young adults...
April 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Srilaxmi Kalavalapalli, Fernando Bril, Jeremy P Koelmel, Kaitlyn Abdo, Joy Guingab, Paige Andrews, Wen-Yi Li, Dhanya Jose, Richard A Yost, Reginald F Frye, Timothy J Garrett, Kenneth Cusi, Nishanth E Sunny
Pioglitazone is effective in improving insulin resistance and liver histology in patients with nonalcoholic steatohepatitis (NASH). Because dysfunctional mitochondrial metabolism is a central feature of NASH, we hypothesized that an important target of pioglitazone would be alleviating mitochondrial oxidative dysfunction. To this end, we studied hepatic mitochondrial metabolism in mice fed high-fructose high trans-fat diet (TFD) supplemented with pioglitazone for 20 weeks, using nuclear magnetic resonance based 13 C-isotopomer analysis...
April 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Lane C Porter, Michael P Franczyk, Terri Pietka, Shintaro Yamaguchi, Jonathan B Lin, Yo Sasaki, Eric Verdin, Rajendra S Apte, Jun Yoshino
Mitochondrial dysfunction in adipose tissue is involved in the pathophysiology of obesity-induced systemic metabolic complications, such as type 2 diabetes, insulin resistance, and dyslipidemia. However, the mechanisms responsible for obesity-induced adipose tissue mitochondrial dysfunction are not clear. The aim of present study was to test the hypothesis that nicotinamide adenine dinucleotide (NAD+ )-dependent deacetylase SIRT3 in adipocytes plays a critical role in adipose tissue mitochondrial biology and obesity...
April 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Jian Zhang, Zheng Xu, Junlian Gu, Saizhi Jiang, Quan Liu, Yang Zheng, Jonathan H Freedman, Jian Sun, Lu Cai
Vascular complications are common pathologies associated with type 1 diabetes. In recent years, histone deacetylation enzyme (HDAC) inhibitors have been shown to be successful in preventing atherosclerosis. To investigate the mechanism for HDAC3 inhibition in preventing diabetic aortic pathologies, male OVE26 type 1 diabetic mice and age-matched wild-type (FVB) mice were given the HDAC3 specific inhibitor RGFP966 or vehicle for three months. These mice were then sacrificed immediately or maintained for additional three months without treatment...
April 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Angelina Hernández-Carretero, Natalie Weber, Samuel A LaBarge, Veronika Peterka, Nhu Y Thi Doan, Simon Schenk, Olivia Osborn
Skeletal muscle is the major site of postprandial peripheral glucose uptake but in obesity-induced insulin resistant states insulin-stimulated glucose disposal is markedly impaired. Despite the importance of skeletal muscle in regulating glucose homeostasis, the specific transcriptional changes associated with insulin sensitive vs. resistant states in muscle remain to be fully elucidated. Herein, using an RNA-seq approach we identified 20 genes differentially expressed in an insulin resistant state in skeletal muscle, including cysteine and glycine-rich protein 3 (Csrp3) that was highly expressed in insulin sensitive conditions, but significantly reduced in the insulin resistant state...
April 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Erika K Tse, Ashkan Salehi, Matthew N Clemenzi, Denise D Belsham
The brain, specifically the hypothalamus, controls whole body energy and glucose homeostasis through neurons that synthesize specific neuropeptides, whereas hypothalamic dysfunction is linked directly to insulin resistance, obesity, and type 2 diabetes mellitus. Nutrient excess, through over-consumption of a Western or high fat diet, exposes the hypothalamus to high levels of free fatty acids, which induces neuroinflammation, endoplasmic reticulum stress, and dysregulation of neuropeptide synthesis. Further, exposure to a high fat diet also disrupts normal circadian rhythms, and conversely, clock gene knockout models have symptoms of metabolic disorders...
April 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Kathleen M Gavin, Karen L Shea, Ellie Gibbons, Pamela Wolfe, Robert S Schwartz, Magaret E Wierman, Wendy M Kohrt
CONTEXT: Sex hormones appear to play a role in the regulation of hypothalamic-pituitary-adrenal (HPA) axis activity. Objective/Outcome Measures. The objective was to isolate the effects of estradiol (E2 ) on central activation of the HPA axis. We hypothesized that the HPA axis response to corticotropin-releasing hormone (CRH) under dexamethasone (Dex) suppression would be exaggerated in response to chronic ovarian hormone suppression and that physiologic E2 add-back would mitigate this response...
April 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Isabel González-Mariscal, Josephine M Egan
April 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Maria Hersom, Hans C Helms, Christoffer Schmalz, Thomas Å Pedersen, Stephen T Buckley, Birger Brodin
Insulin and its receptor are known to be present and functional in the brain. Insulin cerebrospinal fluid concentrations have been shown to correlate with plasma levels of insulin in a non-linear fashion, indicative of a saturable transport pathway from the blood to the brain interstitial fluid. The aim of the present study was to investigate whether insulin was transported across brain endothelial cells in vitro via an insulin receptor-dependent pathway. The study showed that the insulin receptor was expressed at both mRNA and protein level in bovine brain endothelial cells...
March 27, 2018: American Journal of Physiology. Endocrinology and Metabolism
Tae Woo Jung, Yoon Hee Chung, Hyoung-Chun Kim, A M Abd El-Aty, Ji Hoon Jeong
Several studies have demonstrated that protectins, which are ω-3 fatty acid-derived proresolution mediators, may ameliorate inflammation. Recently, protectin DX (PDX) was also reported to attenuate inflammation and insulin resistance in several cell types. However, the effects of PDX on inflammation in adipocytes remain unclear. In this study, we found that PDX treatment suppressed adipogenesis as well as lipid accumulation during 3T3-L1 differentiation. Treatment of differentiated 3T3-L1 cells with PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner...
March 27, 2018: American Journal of Physiology. Endocrinology and Metabolism
Sunmin Park, Da Sol Kim, Eun Seon Kang, Da Bin Kim, Suna Kang
We evaluated the effects of intracerebroventricular administration(ICV) of brain estrogen and progesterone on menopausal symptoms and their effects on the secretion of follicle-stimulating hormone(FSH) and luteinizing hormone(LH) in estrogen-deficient rats. Three weeks after ovariectomy(OVX) or Sham-operation, OVX rats were given ICV infusions of either 17β-estradiol(4 μg/day; ICV-E), progesterone(0.8 μg/day; ICV-P), or vehicle(control) for 4 weeks. OVX rats in the positive-control group were orally provided 150 μg 17β-estradiol/kg bw/day...
March 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
Carine Beysen, Marcie Ruddy, Aubrey Stoch, Lori A Mixson, Kim Rosko, Tim Riiff, Scott M Turner, Marc K Hellerstein, Elizabeth J Murphy
Fructose feeding increases hepatic de novo lipogenesis (DNL) and is associated with non-alcoholic fatty liver disease. Little is known, however, about individual variation in susceptibility to fructose stimulation of DNL. In this three-period, cross-over study, seventeen healthy male subjects were enrolled to evaluate the within and between subject variability of acute fructose feeding on hepatic fractional DNL. During each assessment, [1-13 C1 ]-acetate was infused to measure DNL in the fasting state and during fructose feeding...
March 20, 2018: American Journal of Physiology. Endocrinology and Metabolism
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