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American Journal of Physiology. Endocrinology and Metabolism

Christopher H Emfinger, Zihan Yan, Alecia Welscher, Peter Hung, William McAllister, Paul Hruz, Colin G Nichols, Maria S Remedi
Gain-of-function (GOF) mutations in ATP-sensitive potassium (KATP ) channel cause neonatal diabetes. Despite the well-established genetic root of the disease, the pathways modulating disease severity and treatment effectiveness remain poorly understood. Patient phenotypes can vary from severe diabetes to remission, even in individuals with the same mutation and within the same family; suggesting that subtle modifiers can influence disease outcome. We have tested the underlying mechanism of transient vs permanent neonatal diabetes in KATP -GOF mice treated for 14-days with glibenclamide...
September 18, 2018: American Journal of Physiology. Endocrinology and Metabolism
Rahul Agrawal, Adriana Vieira-de-Abreu, Griffin Durupt, Casey Taylor, Owen Chan, Simon J Fisher
It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia in insulin deficient diabetes may be due to chronic brain insulin deficiency. To test this hypothesis, streptozotocin-diabetic Sprague-Dawley rats were infused with either insulin (3mU/day) or artificial cerebrospinal fluid (aCSF) bilaterally into the ventromedial hypothalamus (VMH) for 2 weeks and compared to nondiabetic rats. Rats underwent hyperinsulinemic (50 .min-1 ) hypoglycemic (~45 mg/dl) clamps. Diabetic rats demonstrated an impaired CRR to hypoglycemia noted by an high glucose infusion rate (GIR) and blunted epinephrine and glucagon responses...
September 18, 2018: American Journal of Physiology. Endocrinology and Metabolism
Sandra G Wai, Paul J Rozance, Stephanie R Wesolowski, William W Hay, Laura D Brown
Overcoming impaired growth in an intrauterine growth restricted (IUGR) fetus has potential to improve neonatal morbidity, long-term growth, and metabolic health outcomes. The extent to which fetal anabolic capacity persists as the IUGR condition progresses is not known. We tested whether prolonged amino acid infusion would increase protein accretion in the IUGR fetus produced from chronic placental insufficiency. IUGR fetal sheep were infused for 10 days with either mixed amino acids providing ~2 g·kg-1 ·day-1 (IUGR-AA) or saline (IUGR-Sal) during late gestation...
September 11, 2018: American Journal of Physiology. Endocrinology and Metabolism
Mizuho Kawakami, Naoko Yokota-Nakagi, Masami Uji, Ken-Ichi Yoshida, Shoko Tazumi, Akira Takamata, Yuki Uchida, Keiko Morimoto
Menopause predisposes women to impaired glucose metabolism, but the role of estrogen remains unclear. In this study, we examined the effects of chronic estrogen replacement on whole-body insulin sensitivity and insulin signaling in ovariectomized rats. Female Wistar rats aged 9 weeks were ovariectomized under anesthesia. After 4 weeks, pellets containing either 17β-estradiol (E2) or placebo (Pla) were subcutaneously implanted into the rats. After 4 weeks of treatment, the intra-abdominal fat accumulation was greater in the Pla group than that in the E2 group...
September 4, 2018: American Journal of Physiology. Endocrinology and Metabolism
Kristoffer Svensson, Jess R Dent, Shahriar Tahvilian, Vitor F Martins, Abha Sathe, Julien Ochala, Mulchand S Patel, Simon Schenk
The pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA and is an important control-point for carbohydrate (CHO) oxidation. However, the importance of the PDC and CHO oxidation to muscle metabolism and exercise performance, particularly during prolonged or high-intensity exercise, has not been fully defined, especially in mature skeletal muscle. To this end, we determined whether skeletal muscle-specific loss of pyruvate dehydrogenase alpha 1 (Pdha1), which is a critical subunit of the PDC, impacts resting energy metabolism, exercise performance or metabolic adaptation to high-fat diet (HFD) feeding...
August 28, 2018: American Journal of Physiology. Endocrinology and Metabolism
Anik Boudreau, Allison J Richard, Jasmine A Burrell, William T King, Ruth Dunn, Jean-Marc Schwarz, David M Ribnicky, Jennifer Rood, J Michael Salbaum, Jacqueline M Stephens
An ethanolic extract of Artemisia scoparia (SCO) has metabolically favorable effects on adipocyte development and function in vitro and in vivo. In diet-induced obese mice, SCO supplementation significantly reduced fasting glucose and insulin levels. Given the importance of adipocyte lipolysis in metabolic health, we tested hypothesized that SCO modulates lipolysis in vitro and in vivo. Free fatty acids and glycerol were measured in the sera of mice fed a high-fat diet with or without SCO supplementation. In cultured 3T3-L1 adipocytes, the effects of SCO on lipolysis were assessed by measuring glycerol and free fatty acid release...
August 28, 2018: American Journal of Physiology. Endocrinology and Metabolism
Shubha Ghosh Dastidar, Ganapathy Jagatheesan, Petra Haberzettl, Jasmit Shah, Bradford G Hill, Aruni Bhatnagar, Daniel J Conklin
Hepatic glutathione S-transferases (GSTs) are dysregulated in human obesity, non-alcoholic fatty liver disease (NAFLD) and diabetes. The multifunctional GST Pi isoform (GSTP) catalyzes the conjugation of glutathione with acrolein and inhibits c-Jun NH2-terminal kinase (JNK) activation. Herein, we tested whether GSTP deficiency disturbs glucose homeostasis in mice. Hepatic GST proteins were downregulated by short-term high-fat diet (HFD) in wild type (WT) mice concomitant with increased glucose intolerance, JNK activation, and cytokine mRNAs in the liver...
August 28, 2018: American Journal of Physiology. Endocrinology and Metabolism
Maryam Syed, Jana P Ball, Keisa W Mathis, Michael E Hall, Michael J Ryan, Marc E Rothenberg, Licy L Yanes Cardozo, Damian G Romero
Primary aldosteronism is characterized by excess aldosterone secretion by the adrenal gland independent of the renin-angiotensin system and accounts for ~10% of hypertensive patients. Excess aldosterone causes cardiac hypertrophy, fibrosis, inflammation and hypertension. The molecular mechanisms that trigger the onset and progression of aldosterone-mediated cardiac injury remain incompletely understood. MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs that have been implicated in multiple cardiac pathologies; however, their regulation and role in aldosterone-mediated cardiac injury and dysfunction remains mostly unknown...
August 28, 2018: American Journal of Physiology. Endocrinology and Metabolism
Sebastien M Labbe, Alexandre Caron, William T Festuccia, Roger Lecomte, Denis Richard
Brown adipose tissue thermogenesis is a key controller of energy metabolism. In response to cold or other adrenergic stimuli, brown adipocytes increase its substrate uptake and oxidative activity while uncoupling ATP synthesis from the mitochondrial respiratory chain activity. Brown adipocytes are found in classic depots such as in the intrerscapular BAT (iBAT). They can also develop in white adipose tissue (WAT), such as in the inguinal WAT (iWAT), where their presence has been associated with metabolic improvements...
August 28, 2018: American Journal of Physiology. Endocrinology and Metabolism
Maria Kupreeva, Abdoulaye Diane, Richard Lehner, Watts Russell, Mahua Ghosh, Spencer D Proctor, Donna F Vine
Polycystic Ovary Syndrome (PCOS) is a highly associated with cardiometabolic risk and the metabolic syndrome (MetS), predisposing women to increased risk of developing Type 2 Diabetes and Cardiovascular Disease (CVD). Metformin is commonly used to treat insulin resistance-glucose intolerance, and flutamide, an androgen receptor antagonist, is used to target hyperandrogenemia and dyslipidemia. Currently, the physiological mechanism of action of these treatments on androgen, lipidogenic and insulin signaling pathways remains unclear in the PCOS...
August 28, 2018: American Journal of Physiology. Endocrinology and Metabolism
David M Klurfeld, Cindy D Davis, Robert W Karp, Emma Allen-Vercoe, Eugene B Chang, Benoit Chassaing, George C Fahey, Bruce R Hamaker, Hannah D Holscher, Johanna W Lampe, Andre Marette, Eric Martens, Stephen J O'Keefe, Devin J Rose, Maria Saarela, Barbara O Schneeman, Joanne L Slavin, Justin L Sonnenburg, Kelly S Swanson, Gary D Wu, Christopher J Lynch
A two-day workshop organized by NIH and USDA included 16 presentations focused on the role of diet in alterations of the human gastrointestinal microbiome, primarily that of the colon. Although thousands of projects have been funded by United States federal funding agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority address dietary effects and a small subset are described in sufficient detail to allow reproduction of a study. While there are standards being developed for many aspects of microbiome studies such as sample collection, nucleic acid extraction, data handling, etc...
August 21, 2018: American Journal of Physiology. Endocrinology and Metabolism
Kensaku Fukunaga, Hitomi Imachi, Jingya Lyu, Tao Dong, Seisuke Sato, Tomohiro Ibata, Toshihiro Kobayashi, Takuo Yoshimoto, Kazuko Yonezaki, Toru Matsunaga, Koji Murao
Recently, several clinical studies have suggested that adult growth hormone deficiency that also has low concentration of IGF1 is associated with an increased prevalence of fatty liver (FL). ABCA1 is a pivotal regulator of lipid efflux from cells to apolipoproteins and play an important role on formation of FL. In this study, we determined the effects of IGF1 on ABCA1 expression in GH deficient mice to clarify its effects on FL. Western blotting, real-time PCR and a luciferase assay were employed to examine the effect of IGF1...
August 21, 2018: American Journal of Physiology. Endocrinology and Metabolism
Haiyan Wang, Edward B Arias, Mark W Pataky, Laurie J Goodyear, Gregory D Cartee
A single exercise session can increase insulin-stimulated glucose uptake (GU) by skeletal muscle concomitant with greater Akt substrate of 160 kDa (AS160) phosphorylation on Akt-phosphosites (Thr642 and Ser588 ) that regulate insulin-stimulated GU. Recent research using mouse skeletal muscle suggested that ex vivo AICAR or electrically stimulated contractile activity inducing increased γ3-AMPK activity and AS160 phosphorylation on a consensus AMPK-motif (Ser704 ) resulted in greater AS160 Thr642 phosphorylation and GU by insulin-stimulated muscle...
August 21, 2018: American Journal of Physiology. Endocrinology and Metabolism
Maxim D Seferovic, Christine A Beamish, Rockann E Mosser, Shannon E Townsend, Kirk Pappan, Vincent Poitout, Kjersti Aagaard, Maureen Gannon
Pancreatic β-cell expansion is a highly regulated metabolic adaptation to increased somatic demands, including obesity and pregnancy; adult β-cells otherwise rarely proliferate. We previously showed that high fat diet (HFD) feeding induces mouse β-cell proliferation in less than one week in the absence of insulin resistance. Here we metabolically profiled tissues from a short-term HFD β-cell expansion mouse model to identify pathways and metabolite changes associated with β-cell proliferation. Mice fed HFD vs CD showed a 14...
August 14, 2018: American Journal of Physiology. Endocrinology and Metabolism
Kathryn Wilsterman, Neta Gotlieb, Lance J Kriegsfeld, George E Bentley
Stress-induced glucocorticoid release is thought to be a primary driver by which maternal stress negatively impacts pregnancy outcomes, but the neuroendocrine targets mediating these adverse outcomes are less well understood. We hypothesized that stress-induced glucocorticoid secretion influences pituitary hormone secretion, resulting in altered ovarian progesterone synthesis. Using a chronic restraint model of stress in mice, we quantified pituitary hormones, steroid hormone production, and expression of ovarian genes that support progesterone production at both early- (day 5) and mid-pregnancy (day 10)...
August 14, 2018: American Journal of Physiology. Endocrinology and Metabolism
Natasha Fillmore, Cory S Wagg, Liyan Zhang, Arata Fukushima, Gary D Lopaschuk
Recent studies have proposed that elevated branched-chain amino acids (BCAAs) may induce insulin resistance (IR) in muscle secondary to increased BCAA oxidation inhibiting glucose oxidation (GO) and fatty acid oxidation (FAO). However, BCAA oxidation rates have not been assessed in muscle IR and cardiac FAO rates are elevated in obesity-associated IR. We examined cardiac BCAA oxidation in mice fed a high fat diet (HFD) to induce IR to better understand the role of cardiac BCAA oxidation in cardiac IR. BCAA oxidation, GO, FAO, and glycolysis were measured in isolated working hearts from mice fed a low fat diet (LFD) or HFD for 10 wk...
August 14, 2018: American Journal of Physiology. Endocrinology and Metabolism
Robert M Edinburgh, Aaron Hengist, Harry A Smith, Rebecca L Travers, Francoise Koumanov, James A Betts, Dylan Thompson, Jean-Philippe Walhin, Gareth A Wallis, D Lee Hamilton, Emma J Stevenson, Kevin D Tipton, Javier T Gonzalez
AIMS: To characterize postprandial glucose flux after exercise in the fed versus overnight fasted-state and to investigate potential underlying mechanisms. METHODS: In a randomized order, twelve men underwent breakfast-rest (BR; 3 h semi-recumbent), breakfast-exercise (BE; 2 h semi-recumbent before 60-min of cycling (50% peak power output) and overnight fasted-exercise (FE; as per BE omitting breakfast) trials. An oral glucose tolerance test (OGTT) was completed post-exercise (post-rest on BR)...
August 14, 2018: American Journal of Physiology. Endocrinology and Metabolism
Teddy Ang, Greg M Kowalski, Clinton R Bruce
Single meal studies have shown that carbohydrate ingestion causes rapid and persistent suppression of endogenous glucose production (EGP). However, little is known about the regulation of EGP under real-life eating patterns where multiple carbohydrate-containing meals are consumed throughout the day. Therefore, we aimed to characterize the regulation of EGP in response to sequential meals, specifically during the breakfast-lunch transition. Nine healthy individuals (5 males, 4 females; 32 ± 2 years; 25.0 ± 1...
August 14, 2018: American Journal of Physiology. Endocrinology and Metabolism
Mathijs Drummen, Elke Dorenbos, Anita Ce Vreugdenhil, Anne Raben, Mikael Fogelholm, Margriet S Westerterp-Plantenga, Tanja Adam
AIMS: To assess the effects of a weight maintenance period comprising two diets differing in protein intake, after weight loss, on intrahepatic lipid content and implications for insulin sensitivity. MATERIALS AND METHODS: A total of 25 participants (BMI: 31.1±3.5 kg/m2; intrahepatic lipid (IHL): 8.7±8.3%; fasting glucose: 6.4±0.6 mmol/l; HOMA-IR: 3.7±1.6; Matsuda index: 3.4±2.9) started an 8-week low energy diet followed by a 2-year weight maintenance period with either high protein (HP) or medium protein (MP) dietary guidelines...
August 7, 2018: American Journal of Physiology. Endocrinology and Metabolism
Daniel B Harmon, Chao Wu, Nikolas Dedousis, Ian J Sipula, Maja Stafanovic-Racic, Gabriele Schoiswohl, Christopher P O'Donnell, Laura C Alonso, Erin E Kershaw, Eric E Kelley, Robert M O'Doherty
Accumulation of myeloid cells in the liver, notably dendritic cells (DC) and monocytes/macrophages (MC), is a major component of the metainflammation of obesity. However, the mechanism(s) stimulating hepatic DC/MC infiltration remain ill-defined. Herein, we addressed the hypothesis that adipose tissue (AT) free fatty acids (FFA) play a central role in the initiation of hepatic DC/MC accumulation, using a number of mouse models of altered FFA supply to the liver. In two models of acute FFA elevation (lipid infusion and fasting) hepatic DC/MC and triglycerides (TG), but not AT DC/MC, were increased without altering plasma cytokines (PC; TNFα and MCP-1), and with variable effects on oxidative stress (OxS) markers...
August 7, 2018: American Journal of Physiology. Endocrinology and Metabolism
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