PubMed Journal Database | American journal of physiology. Endocrinology and metabolism

Corrigendum.

Advantage of predictive modeling in tracer studies.

Reply to Russell: VLDL-TG kinetics: how to interpret a dual-isotope study.

Subcellular localization dependent decrements in skeletal muscle glycogen and mitochondria content following short-term disuse in young and old men.

Previous studies show that skeletal muscle glycogen and mitochondria are distributed in distinct subcellular localizations, but the role and regulation of these subcellular localizations are unclear. In the present study, we used transmission electron microscopy to investigate the effect of disuse and aging on human skeletal muscle glycogen and mitochondria content in subsarcolemmal (SS), intermyofibrillar (IMF) and intramyofibrillar (Intra) localizations. Five young (~23 yrs) and five old (~66 yrs) recreat...

Signaling and cytotoxic functions of 4-Hydroxyalkenals.

The peroxidation of n-3 and n-6 polyunsaturated fatty acids (PUFAs) and of their hydroperoxy metabolites is a complex process. It is initiated by free oxygen radical-induced abstraction of a hydrogen atom from the lipid molecule, followed by a series of non-enzymatic reactions that ultimately generate the reactive aldehyde species 4-hydroxyalkenals. The molecule 4-hydroxyl-2E-hexenal (4-HHE) is generated by peroxidation of n-3 PUFAs, such as linolenic acid, eicosapentaenoic acid and docosahexaenoic acid. Th...

Homocysteine impairs coronary artery endothelial function by inhibiting tetrahydrobiopterin in patients with hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) has been associated with impaired vascular endothelial function. Our previous study demonstrated significantly higher secretion of the chemokine monocyte chemoattractant protein 1 (MCP-1) from monocytes in response to lipopolysaccharide in patients with HHcy. In the present study, we investigated whether coronary endothelial function was damaged in patients with chronic HHcy (plasma level of homocysteine > 15 μmol/l), and if so, whether this impaired endothelial function is indu...

MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic {beta}-cell proliferation in islets from early lactating mothers.

Maternal pancreatic islets undergo a robust increase of mass and proliferation during pregnancy, which allows a compensation of gestational insulin resistance. Studies have described that this adaptation switches to a low proliferative status after the delivery. The mechanisms underlying this reversal are unknown but the action of glucocorticoids (GCs) is believed to play an important role, because GCs counteract the pregnancy-like effects of prolactin on isolated pancreatic islets maintained in cell cultur...

Intraspecies disparity in growth rate is associated with differences in expression of local growth plate regulators.

Disparities in longitudinal growth within a species can partly be explained by endocrinological differences. We hypothesized that regulatory networks acting locally in the growth plate may also be important. We tested this hypothesis by evaluating the IGF/IGFBP expression, the vitamin D pathway and the PTHrP-Indian Hedgehog (IHH) feedback loop in rib growth plates from 10- and 21-week-old small (Miniature Poodles, MP) and large breed dogs (Great Danes, GD) using immunohistochemistry and quantitative (q) PCR...

Prepubertal urinary estrogen excretion and its relationship with pubertal timing.

Whether prepubertal estrogen production impacts on the timing of puberty is not clear. We aimed to investigate prepubertal 24-h estrogen excretion levels and their association with early and late pubertal markers. Daily urinary excretion rates of estrogens of 132 healthy children, who provided 24-h urine samples 1 and 2 years before the start of the pubertal growth spurt (age at take-off, ATO), were quantified by stable isotope dilution/GC-MS. E-sum3 (estrone+estradiol+estriol) was used as a marker for pote...

Plasma lipoproteins are required for both basal and stress-induced adrenal glucocorticoid synthesis and protection against endotoxemia in mice.

Lipoprotein-associated cholesterol has been suggested to make a significant contribution to adrenal steroidogenesis in vivo. To determine whether lipoproteins indeed do contribute to optimal adrenal steroidogenesis in mice, in the current study we have determined the effect of relative lipoprotein deficiency on adrenal steroidogenesis in C57BL/6 wild-type mice. Feeding C57BL/6 mice the lipid-lowering drug probucol (0.25% w/w) for two weeks induced a 90% decrease in plasma high-density lipoprotein (HDL)-chol...

PRENATAL TESTOSTERONE EXCESS ALTERS SERTOLI AND GERM CELL NUMBER AND TESTICULAR FSH RECEPTOR EXPRESSION IN RAMS.

Exposure to excess testosterone (T) during fetal life has a profound impact on the metabolic and reproductive functions in the female's postnatal life. However, less is known about the effects of excess testosterone in males. The aim of the present study was to evaluate the impact (consequences) of an excess of T during fetal development on mature male testis. The testicular evaluation was by histological analysis and by determination of mRNA expression of the FSH receptor (FSH-R), transforming growth facto...

Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level.

The hypothalamic-pituitary-thyroid (HPT) axis is a major contributor in maintaining energy expenditure and body weight, and the adipocyte hormone leptin regulates this axis by increasing thyrotropin-releasing hormone (TRH) levels in the fed state. Leptin stimulates TRH directly in the hypothalamic paraventricular nucleus (PVN; direct pathway) and indirectly by regulating proopiomelnocortin (POMC) neurons in the hypothalamic arcuate nucleus (ARC; indirect pathway). While the indirect pathway is fully functio...

{alpha}-Synuclein Binds the KATP Channel at Insulin Secretory Granules and Inhibits Insulin Secretion.

α-Synuclein has been studied in numerous cell types often associated with secretory processes. In pancreatic β cells, α-synuclein might therefore play a similar role by interacting with organelles involved in insulin secretion. We tested for α-synuclein localizing to insulin secretory granules and characterized its role in glucose-stimulated insulin secretion. Immuno-histochemistry and fluorescent sulfonylureas were used to test for α-synuclein localization to insulin granules in β cells, immunoprecip...

Decidual PTEN expression is required for trophoblast invasion in the mouse.

Trophoblast invasion likely depends on complex crosstalk between the fetal and maternal tissues and may involve the modulation of PI3K/AKT signaling activity in maternal decidual cells. In this report, we studied implantation in Pten(tm1Hwu/tm1Hwu);Amhr2(tm3(cre)Bhr/+) mice, which lack the PI3K signaling antagonist gene Pten in myometrial and stromal/decidual cells. Primiparous Pten(tm1Hwu/tm1Hwu);Amhr2(tm3(cre)Bhr/+) mice were found to be subfertile due to increased fetal mortality at e11.5. Histopathologi...

Arginine-Induced Stimulation of Protein Synthesis and Survival in IPEC-J2 Cells Is Mediated by mTOR But not Nitric Oxide.

Arginine (ARG) is an indispensable amino acid in neonates and required for growth. Neonatal intestinal epithelial cells (IEC) are capable of ARG transport, catabolism and synthesis, and express nitric oxide synthase (NOS) to produce NO from ARG. Our aim was to determine whether ARG directly stimulates IEC growth and protein synthesis and whether this effect is mediated via mammalian target of rapamycin (mTOR) and NO-dependent. We studied neonatal porcine IEC (IPEC-J2) cultured in serum- and ARG-free medium...

Beta cell-specific pyruvate dehydrogenase deficiency impairs glucose-stimulated insulin secretion.

Glucose-stimulated insulin secretion (GSIS) by β-cells requires the generation of ATP which is dependent on coupling factors involving three different pyruvate cycling shuttles (anaplerosis and cataplerosis). The roles of several key enzymes involved in pyruvate cycling in β-cells have been documented using isolated islets and β-cell clonal lines. To investigate the role of the pyruvate dehydrogenase (PDH) complex (PDC) in GSIS, a murine model of β-cell-specific PDH deficiency (β-PDHKO) was created. Pa...

Adipose tissue macrophages in insulin resistant subjects are associated with collagen VI, fibrosis and demonstrate alternative activation.

Adipose tissue macrophages are associated with insulin resistance and are linked with changes in the extracellular matrix (ECM). To better characterize adipose macrophages, the ECM, and adipocyte-macrophage interactions, gene expression from adipose tissue and stromal vascular fraction was assessed for markers of inflammation and fibrosis, and macrophages from obese and lean subjects were counted and characterized immunohistochemically. Coculture experiments examined the effects of adipocyte-macrophage inte...

SGLT1 protein expression in plasma membrane of acinar cells correlates with the sympathetic outflow to salivary glands in diabetic and hypertensive rats.

Salivary gland dysfunction is a feature in diabetes and hypertension. We hypothesized that the sodium-glucose cotransporter 1 (SGLT1) participates on salivary dysfunctions, through a sympathetic- and protein kinase A- (PKA) mediated pathway. In Wistar-Kyoto rats (WKY), diabetic WKY (WKY-D), spontaneously hypertensive rats (SHR) and diabetic SHR (SHR-D), PKA/SGLT1 proteins were analyzed in parotid and submandibular glands, and the sympathetic nerve activity (SNA) to the glands was monitored. Basal SNA was 3-...

Chronic consumption of a high fat/high fructose diet renders the liver incapable of net hepatic glucose uptake.

The objective of this study was to assess the response of a large animal model to high dietary fat and fructose (HFFD). Three different metabolic assessments were performed during 13 weeks of feeding a HFFD (n=10) or chow control (CTR, n=4) diet: oral glucose tolerance tests (OGTTs; baseline, 4, and 8 weeks), hyperinsulinemic-euglycemic clamps (HIEGs; baseline and 10 weeks) and hyperinsulinemic-hyperglycemic clamps (HIHGs, 13 weeks). The delta AUC for glucose during the OGTTs more than doubled after 4 and 8...

Part II: Treatment with a CRH-R1 Antagonist Prevents Stress-Induced Suppression of the Central Neural Drive to the Reproductive Axis in Female Macaques.

In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., are stress-sensitive), while others are more stress-resilient. When exposed to mild combined psychosocial + metabolic stress (change in social environment + reduced diet), female cynomolgus monkeys can be categorized as stress-sensitive ("SS"; rapidly become anovulatory in response to stress), medium stress-resilient ("MSR"; slowly become anovulatory in response to prolonged stress), or highly stress-resili...

Journey Between Scylla and Charibdis Through Storms of Carbohydrate Metabolism and Diabetes: A Career Retrospective.

This research perspective allowed me to summarize some of my work completed over 50 years, and it is organized in 7 sections. 1) The treatment of diabetes concentrates on the liver, and/or the periphery. We quantified hormonal and metabolic interactions involved in physiology and the pathogenesis of diabetes by developing tracer methods to separate the effects of diabetes on both. We collaborated in the first tracer clinical studies on insulin resistance, hypertriglyceridemia, and the Cori cycle. 2) Diabete...

Sustained Activation of Renal N-Methyl-D-Aspartate Receptors decreases Vitamin D synthesis. A possible role for Glutamate on the onset of secondary HPT.

N-methyl-D-aspartate receptors (NMDAr) are tetrameric amino acid receptors which act as membrane calcium channels. The presence of the receptor has been detected in the principal organs responsible for calcium homeostasis (kidney, bone and parathyroid gland), pointing to a possible role in mineral metabolism. The aim of this study is to test the effect of NMDAr activation in the kidney and in 1,25(OH)(2)D(3) synthesis. We determined the presence of NMDAr subunits in human kidney cells (HK-2) and proved its...

Fructose: A highly lipogenic nutrient implicated in insulin resistance, hepatic steatosis and metabolic syndrome.

As dietary exposure to fructose has increased over the past 40 years, there is growing concern that high fructose consumption in humans may be in part responsible for the rising incidence of obesity worldwide. Obesity is associated with a host of metabolic challenges, collectively termed the metabolic syndrome. Fructose is a highly lipogenic sugar that has profound metabolic effects in the liver and has been associated with many of the components of the metabolic syndrome (insulin resistance, elevated waist...

IL-6 selectively stimulates fat metabolism in human skeletal muscle.

Interleukin (IL)-6 is chronically elevated in type 2 diabetes but also during exercise. However, the exact metabolic role, and hence the physiological significance, has not been elucidated. The objective of this study was to investigate the in vivo effect of rhIL-6 on human fat and glucose metabolism and signalling of both adipose tissue and skeletal muscle. Eight healthy post-absorptive males were infused with either rhIL-6 or saline for 4 hours eliciting IL-6 levels of ~40 and ~1 pg mL(-1), respectively....

A high-fat, ketogenic diet causes hepatic insulin resistance in mice despite increasing energy expenditure and preventing weight gain.

Low-carbohydrate, high-fat ketogenic diets (KD) have been suggested to be more effective in promoting weight loss than conventional caloric restriction, whereas their effect on hepatic glucose and lipid metabolism and the mechanisms by which they may promote weight loss remain controversial. The aim of this study was to explore the role of KD on liver and muscle insulin sensitivity, hepatic lipid metabolism, energy expenditure and food intake. We studied insulin action in mice fed KD or regular chow (RC) us...