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American Journal of Physiology. Endocrinology and Metabolism

Marina Sokolova, Afaf Sahraoui, Merete Høyem, Jonas Øgaard, Egil Lien, Pål Aukrust, Arne Yndestad, Trine Ranheim, Hanne Scholz
Inflammasomes are multi-protein inflammatory platforms that induce caspase-1 activation and subsequently interleukin (IL)-1β and IL-18 processing. The NLRP3 inflammasome is activated by different forms of oxidative stress, and based on the central role of IL-1β in the destruction of pancreatic islets, it could be related to the development of diabetes. We therefore investigated responses in wild-type C57Bl/6 (WT), NLRP3-/- and ASC-/- mice after exposing islets to short-term hypoxia or alloxan induced islet damage...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Yingxue Wang, Bridgette A Christopher, Kirkland A Wilson, Deborah Muoio, Robert W McGarrah, Henri Brunengraber, Guo-Fang Zhang
High concentrations of propionate and its metabolites are found in several diseases that are often associated with the development of cardiac dysfunction, such as obesity, diabetes, propionic acidemia, and methylmalonic acidemia. In the present work, we employed a stable isotope-based metabolic flux approach to understand propionate-mediated perturbation of cardiac energy metabolism. Propionate led to accumulation of propionyl-CoA (increased by ~101-fold) and methylmalonyl-CoA (increased by 36-fold). This accumulation caused significant mitochondrial CoA trapping and inhibited fatty acid oxidation...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Qing Wen, Elizabeth I Tang, Wing-Yee Lui, Will M Lee, Chris K C Wong, Bruno Silvestrini, C Yan Cheng
In the mammalian testis, spermatogenesis is dependent on the microtubule (MT)-specific motor proteins such as dynein 1 that serve as the engine to support germ cell transport. Yet the underlying molecular mechanism(s) remain unknown. Herein, we used RNAi to knockdown dynein 1 heavy chain (Dync1h1) and an inhibitor ciliobrevin D to inactivate dynein in Sertoli cells in vitro and the testis in vivo, thereby probing the role of dynein 1 in spermatogenesis. Both treatments were shown to induce extensively disruption of MT organization across Sertoli cells in vitro and the testis in vivo...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Mary Frances Lopez, Lingyun Zheng, Ji Miao, Reddy Gali, Grzegorz Gorski, Joel N Hirschhorn
Newborns with intrauterine growth-restriction are at increased risk of mortality and life-long co-morbidities. Insulin-like growth factor-II (IGF2) deficiency in humans as well as in mice leads to intrauterine growth restriction and decreased neonatal glycogen stores. The present study aims to further characterize the metabolic and transcriptional consequences of Igf2 deficiency in the newborn. We found that, despite being born significantly smaller than their wild-type (Igf2+/+ ) littermates, brain size was preserved in Igf2 knockout (Igf2-/- ), consistent with nutritional deficiency...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Han-Chow E Koh, Niels Ørtenblad, Kamilla M Winding, Ylva Hellsten, Stefan P Mortensen, Joachim Nielsen
This study compared the effects of moderate-intensity endurance training and high-intensity interval training on fiber type-specific subcellular volumetric content and morphology of lipid droplets and mitochondria in skeletal muscles of type 2 diabetic patients. Sixteen sedentary type 2 diabetic patients (57±7 years old) were randomized to complete 11 weeks of either 40-min cycling at 50% peak workload (Endurance, n = 8) or 10 1-min cycling intervals at 95% peak workload separated by 1 min of recovery (High-intensity Interval, n = 8), 3 times per week...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Kikumi D Ono-Moore, Michael L Blackburn, Sean H Adams
Based primarily on cell culture results, saturated fatty acids (SFAs) are proposed to promote inflammation and contribute to metabolic dysfunction through toll-like receptor activation. Studies are often complicated by a requirement for carriers (e.g. BSA) or solvents (e.g. ethanol) to increase SFA solubility. To ascertain if these factors influence interpretations of SFA-associated inflammation activity, we measured responses of RAW264.7 monocyte/macrophages and C2C12 myotubes to various BSA, ethanol and cyclodextrin (alternative FA carrier) conditions...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Brian D Piccolo, James L Graham, Kimber L Stanhope, Intawat Nookaew, Kelly E Mecer, Sree V Chintapalli, Umesh D Wankhade, Kartik Shankar, Peter J Havel, Sean H Adams
The composition of the gut microbiome is altered in obesity and type 2 diabetes; however, it is not known whether these alterations are mediated by dietary factors or related to declines in metabolic health. To address this, cecal contents were collected from age-matched, chow-fed male UCD-T2DM rats before the onset of diabetes (pre-diabetic PD, n=15); 2 wk recently-diabetic (RD, n=10); 3 mo (D3M, n=11); and 6 mo (D6M, n=8) post-onset of diabetes. Bacterial species and functional gene counts were assessed by shotgun metagenomic sequencing of bacterial DNA in cecal contents, while metabolites were identified by GC-QTOF-MS...
July 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
Fumika Shigiyama, Naoki Kumashiro, Yousuke Tsuneoka, Hiroyuki Igarashi, Fukumi Yoshikawa, Saori Kakehi, Hiromasa Funato, Takahisa Hirose
Sleep deprivation is associated with increased risk for type 2 diabetes mellitus. However, the underlying mechanisms of sleep deprivation-induced glucose intolerance remain elusive. The aim of this study was to investigate the mechanisms of sleep deprivation-induced glucose intolerance in mice with a special focus on the liver. We established a mouse model of sleep deprivation-induced glucose intolerance using C57BL/6J male mice. A single 6-hr sleep deprivation by the gentle handling method under fasting condition induced glucose intolerance...
July 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Mugdha V Joglekar, Wilson Wong, Cody-Lee Maynard, Malati R Umrani, David Martin, Thomas Loudovaris, Helen E Thomas, Louise T Dalgaard, Anand A Hardikar
Inappropriate insulin secretion from β-cells is considered as an early sign of impaired glucose tolerance and Type 2 diabetes (T2D). Glucokinase (GCK) is an important enzyme that regulates glucose metabolism and ensures that the normal circulating glucose concentrations are maintained. GCK expression is induced by glucose and regulated via transcription factors and regulatory proteins. Recently, microRNA-206 (miR-206) was reported to regulate GCK and alter glucose tolerance in normal and high fat diet-fed mice...
July 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Yanchun Li, Zhongyang Lu, Ji Hyun Ru, Maria F Lopes-Virella, Timothy J Lyons, Yan Huang
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and consumption of high-fat diet (HFD) is a risk factor for NAFLD. The HFD not only increases intake of saturated fatty acid (SFA), but also induces metabolic endotoxemia, a HFD-associated increase in circulating lipopolysaccharide (LPS). Although it is known that SFA or LPS promotes hepatic inflammation, a hallmark of NAFLD, it remains unclear how SFA in combination with LPS stimulates host inflammatory response in hepatocytes...
July 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Christian Wolfrum, Elke Kiehlmann, Pawel Pelczar
Brown adipose tissue (BAT) has the unique ability of converting energy stored in the form of triglycerides into heat. This property makes BAT a target tissue to increase energy expenditure and improve systemic metabolic control. TRPC1 is a founding member of the TRP protein family that also includes several temperature-sensitive channels. We show that TRPC1 is highly expressed in all adipocyte depots, including BAT, and that Trpc1-deficient mice are prone to weight gain and manifest reduced metabolic control...
July 10, 2018: American Journal of Physiology. Endocrinology and Metabolism
Randall F D'Souza, Jonathan S T Woodhead, Nina Zeng, Cherie Blenkiron, Troy L Merry, David Cameron-Smith, Cameron J Mitchell
MicroRNAs (miRNAs) regulate gene expression via transcript degradation and translational inhibition, they may also function as long distance signalling molecules. Circulatory miRNAs are either protein bound or packaged within vesicles (exosomes). Ten young men (24.6{plus minus}4.0 years) underwent a single bout of high intensity interval cycling exercise. Vastus lateralis biopsies and plasma were collected immediately before and after exercise, as well as 4 hours following the exercise bout. 29 miRNAs previously reported to be regulated by acute exercise were assessed within muscle, venous plasma and enriched circulatory exosomes via qRT-PCR...
July 3, 2018: American Journal of Physiology. Endocrinology and Metabolism
Yu Zhou, Lishan Huang, Wenting Zheng, Jingjing An, Zhidong Zhan, Linxi Wang, Zhou Chen, Libin Liu
Recurrent non-severe hypoglycemia (RH) can lead to cognitive dysfunction in diabetic patients, although the involved mechanisms remain unclear. Here, we aimed to investigate the mechanism underlying RH-induced cognitive deficits with a focus on mitochondrial homeostasis. To establish a model that mimicked RH in type 1 diabetic (T1DM) patients receiving insulin therapy, streptozotocin (STZ)-induced mice with T1DM were subjected to recurrent, twice-weekly, insulin injections over 4 weeks. We found that RH disrupted the mitochondrial fine structure, reduced the number of mitochondria, and upregulated the expression of mitochondrial dynamics and mitophagy markers, including dynamin-related protein 1 (Drp1), Bcl-2/adenovirus E1B 19-kDa-interacting protein-3 (BNIP3), and LC3 in the hippocampus of T1DM mice...
July 3, 2018: American Journal of Physiology. Endocrinology and Metabolism
Gabriella A Heruc, Tanya J Little, Michael R Kohn, Sloane Madden, Simon D Clarke, Michael Horowitz, Christine Feinle-Bisset
Postprandial glucose is reduced in malnourished patients with anorexia nervosa (AN), but the mechanisms and duration for this remain unclear. We examined blood glucose, gastric emptying and glucoregulatory hormone changes in malnourished patients with AN, and during two weeks of acute refeeding, compared with healthy controls (HCs). 22 female adolescents with AN and 17 age-matched female HCs were assessed after a 4-hour fast. Patients were commenced on a refeeding protocol of 2400 kcal/day. Gastric emptying (13 C-octanoate breath-test), glucose absorption (3-O-methylglucose), blood glucose, plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and glucagon responses to a mixed-nutrient test-meal were measured on admission and one and two weeks post-refeeding...
July 3, 2018: American Journal of Physiology. Endocrinology and Metabolism
Chantel Kowalchuk, Laura Castellani, Araba Chintoh, Gary Remington, Adria Giacca, Margaret Hahn
Since the serendipitous discovery of the first antipsychotic (AP) drug in the 1950's, APs remain the cornerstone of treatment for schizophrenia. A shift over the past two decades away from first generation, conventional APs to so-called "atypical" (or second/ third generation) APs parallels acknowledgment of serious metabolic side-effects. As will be reviewed, AP drugs and type 2 diabetes are now inextricably linked, likely contributing to the 2-3-fold increased risk of type 2 diabetes observed in schizophrenia...
July 3, 2018: American Journal of Physiology. Endocrinology and Metabolism
Ana Isabel Martin, Ana Belen Gómez-SanMiguel, Teresa Priego, Asuncion Lopez-Calderon
Inflammatory diseases are associated with muscle wasting as a result of an increase in proteolysis. The purpose of this study was to elucidate whether administration of a beta-2 adrenergic agonist, formoterol, was able to prevent the acute effects of sepsis-induced by liposaccharide (LPS) injection on rat gastrocnemius and to evaluate the possible role of corticosterone, IGF-I, miR-23a and miR-29b. For this purpose, male Wistar rats were injected with LPS and/or formoterol. Formoterol treatment decreased LPS-induced increase in serum corticosterone, TNFα upregulation as well as NF-κB(p65) and FoxO1 activation in the gastrocnemius...
July 3, 2018: American Journal of Physiology. Endocrinology and Metabolism
Jennifer D Deem, Kenjiro Muta, Kayoko Ogimoto, Jarrell T Nelson, Kevin R Velasco, Karl J Kaiyala, Gregory J Morton
The ability to maintain core temperature within a narrow range despite rapid and dramatic changes in environmental temperature is essential for the survival of free-living mammals, and growing evidence implicates an important role for the hormone, leptin. Given that thyroid hormone plays a major role in thermogenesis, and circulating thyroid hormone levels are reduced in leptin-deficient states - an effect partially restored by leptin replacement - we sought to determine the extent to which leptin's role in thermogenesis is mediated by raising thyroid hormone levels...
June 26, 2018: American Journal of Physiology. Endocrinology and Metabolism
Fenghua Zeng, Yinqiu Wang, Lance A Kloepfer, Suwan Wang, Raymond C Harris
ErbB4, a member of the EGF receptor family, plays a variety of roles in physiologic and pathologic states. Genetic studies have indicated linkage of ErbB4 and type II diabetes and obesity, but its role in metabolic syndrome (MetS) has not been reported. In the current study, we found that compared to wild-type, mice with ErbB4 deletion developed MetS after 24 weeks on a medium-fat diet (MFD) as indicated by development of obesity, dyslipidemia, hepatic steatosis, hyperglycemia, hyperinsulinemia, and insulin resistance...
June 26, 2018: American Journal of Physiology. Endocrinology and Metabolism
Suman Srinivasa, Anna Aulinas, Timothy O'Malley, Patrick Maehler, Gail K Adler, Steven K Grinspoon, Elizabeth A Lawson
INTRODUCTION: Oxytocin, while classically known for its role in parturition, lactation and social behavior, also has been implicated in the control of sodium homeostasis in animal models. To improve our understanding of oxytocin physiology in humans, we measured basal oxytocin levels under low and liberal dietary sodium conditions and following a peripheral Angiotensin II (Ang II) infusion. METHODS: Ten healthy individuals underwent a 6-day standardized low sodium diet and a 6-day liberal sodium diet...
June 26, 2018: American Journal of Physiology. Endocrinology and Metabolism
Yoshinao Kobayashi, Akiko Eguchi, Mina Tempaku, Tatsuro Honda, Kenji Togashi, Motoh Iwasa, Hiroshi Hasegawa, Yoshiyuki Takei, Yasuhiro Sumida, Osamu Taguchi
We have reported that hypertrophic adipocytes release extracellular vesicles (EVs) and that number of circulating adipocyte-derived EVs correlated with insulin and homeostasis model assessment-insulin resistance (HOMA-IR) in a pilot study using obese patients. Here, we explored the association between circulating EV level and various metabolic parameters, including obesity and lipid and glucose metabolisms among 203 subjects (76 men, 127 women; median age, 54 years) with or without risk factor for metabolic diseases, who received a 75-g oral glucose tolerance test (OGTT)...
June 26, 2018: American Journal of Physiology. Endocrinology and Metabolism
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