Development of a reliable automated screening system to identify small molecules and biologics that promote human {beta}-cell regeneration
Numerous compounds stimulate rodent β-cell proliferation; however, translating these findings to human β-cells remains a challenge. To examine human β-cell proliferation in response to such compounds, we developed a medium-throughput in vitro method of quantifying adult human β-cell proliferation markers. This method is based on high-content imaging of dispersed islet cells seeded in 384-well plates and automated cell counting that identifies fluorescently labeled β-cells with high specificity using both nuclear and cytoplasmic markers. β-Cells from each donor were assessed for their function ...
Source: AJP: Endocrinology and Metabolism - November 14, 2016 Category: Endocrinology Authors: Aamodt, K. I., Aramandla, R., Brown, J. J., Fiaschi-Taesch, N., Wang, P., Stewart, A. F., Brissova, M., Powers, A. C. Tags: Articles Source Type: research
Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents
Only a handful of studies, primarily in clinical samples, have reported an association between obesity, inflammation, and obstructive sleep apnea (OSA) in children and adolescents. No studies, however, have examined the pathogenetic link between visceral adiposity, systemic inflammation, and incident OSA in a large general population sample using objective measures of sleep and body fat. Adolescents (n = 392; mean age 17.0 ± 2.2 yr, 54.0% male) from the Penn State Child Cohort (PSCC) underwent 9-h overnight polysomnography; a DXA scan to assess body fat distribution; and a single fasting blood draw for the assessmen...
Source: AJP: Endocrinology and Metabolism - November 14, 2016 Category: Endocrinology Authors: Gaines, J., Vgontzas, A. N., Fernandez-Mendoza, J., Calhoun, S. L., He, F., Liao, D., Sawyer, M. D., Bixler, E. O. Tags: Call for Papers Source Type: research
Retraction
(Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 31, 2016 Category: Endocrinology Tags: Retraction Source Type: research
Protein coingestion with alcohol following strenuous exercise attenuates alcohol-induced intramyocellular apoptosis and inhibition of autophagy
Alcohol ingestion decreases postexercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation is unknown. Autophagy is an intracellular "recycling" system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise. In a randomized crossover design, eight physically active males completed three experimental trials of concurr...
Source: AJP: Endocrinology and Metabolism - October 31, 2016 Category: Endocrinology Authors: Smiles, W. J., Parr, E. B., Coffey, V. G., Lacham-Kaplan, O., Hawley, J. A., Camera, D. M. Tags: Articles Source Type: research
Saturated fatty acids activate caspase-4/5 in human monocytes, triggering IL-1{beta} and IL-18 release
Obesity is associated with metabolic tissue infiltration by monocyte-derived macrophages. Saturated fatty acids contribute to proinflammatory gene induction in tissue-embedded immune cells. However, it is unknown how circulating monocytes, the macrophage precursors, react to high-fat environments. In macrophages, saturated fatty acids activate inflammatory pathways and, notably, prime caspase-associated inflammasomes. Inflammasome-activated IL-1β contributes to type 2 diabetes. We hypothesized that 1) human monocytes from obese patients show caspase activation, and 2) fatty acids trigger this response and consequent r...
Source: AJP: Endocrinology and Metabolism - October 31, 2016 Category: Endocrinology Authors: Pillon, N. J., Chan, K. L., Zhang, S., Mejdani, M., Jacobson, M. R., Ducos, A., Bilan, P. J., Niu, W., Klip, A. Tags: Articles Source Type: research
Novel single skeletal muscle fiber analysis reveals a fiber type-selective effect of acute exercise on glucose uptake
One exercise session can induce subsequently elevated insulin sensitivity that is largely attributable to greater insulin-stimulated glucose uptake by skeletal muscle. Because skeletal muscle is a heterogeneous tissue comprised of diverse fiber types, our primary aim was to determine exercise effects on insulin-independent and insulin-dependent glucose uptake by single fibers of different fiber types. We hypothesized that each fiber type featuring elevated insulin-independent glucose uptake immediately postexercise (IPEX) would be characterized by increased insulin-dependent glucose uptake at 3.5 h postexercise (3.5hPEX). ...
Source: AJP: Endocrinology and Metabolism - October 31, 2016 Category: Endocrinology Authors: Cartee, G. D., Arias, E. B., Yu, C. S., Pataky, M. W. Tags: Articles Source Type: research
Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review
The precise role of age-related muscle anabolic resistance in the progression of sarcopenia and functional decline in older individuals is unclear. The present aim was to assess whether the muscle protein synthesis (MPS) response to acute exercise (endurance or resistance) and/or amino acid-based nutrition is attenuated in older compared with young individuals. A systematic review was conducted on studies that directly examined the influence of age on the MPS response to exercise and/or amino acid-based nutrition. Each study arm was synthesized and reported as providing sufficient or insufficient "evidence of age-related m...
Source: AJP: Endocrinology and Metabolism - October 31, 2016 Category: Endocrinology Authors: Shad, B. J., Thompson, J. L., Breen, L. Tags: Call for Papers Source Type: research
Reply to letter to the editor: the tolerance of erythritol and xylitol based on effective dose methodologies
(Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 11, 2016 Category: Endocrinology Authors: Wölnerhanssen, B. K., Meyer Gerspach, A. C., Beglinger, C. Tags: Letter to the Editor Source Type: research
The tolerance of erythritol and xylitol based on effective dose methodologies
(Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 11, 2016 Category: Endocrinology Authors: Bonnema, A., DeCock, P., Eapen, A., Bosscher, D. Tags: Letter to the Editor Source Type: research
Aerobic capacity and hepatic mitochondrial lipid oxidation alters susceptibility for chronic high-fat diet-induced hepatic steatosis
In conclusion, intrinsically high aerobic capacity confers protection against HFD-induced hepatic steatosis through elevated hepatic mitochondrial oxidative capacity. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 11, 2016 Category: Endocrinology Authors: Morris, E. M., Meers, G. M. E., Koch, L. G., Britton, S. L., Fletcher, J. A., Fu, X., Shankar, K., Burgess, S. C., Ibdah, J. A., Rector, R. S., Thyfault, J. P. Tags: Articles Source Type: research
Healthy glucocorticoid receptor N363S carriers dysregulate gene expression associated with metabolic syndrome
We examined the function of the N363S SNP in a cohort of subjects from the general population of North Carolina. Eighteen N363S heterozygous carriers and 36 noncarrier, control subjects were examined for clinical and biochemical parameters followed by a low-dose dexamethasone suppression test to evaluate glucocorticoid responsiveness. Serum insulin measurements revealed that N363S carriers have higher levels of insulin, although not statistically significant, compared with controls. Glucocorticoid receptor protein levels evaluated in peripheral blood mononuclear cells from each clinical subject showed no difference between...
Source: AJP: Endocrinology and Metabolism - October 11, 2016 Category: Endocrinology Authors: Jewell, C. M., Katen, K. S., Barber, L. M., Cannon, C., Garantziotis, S., Cidlowski, J. A. Tags: Call for Papers Source Type: research
Treatment of nonalcoholic fatty liver disease: role of AMPK
Nonalcoholic fatty liver disease (NAFLD) is a growing worldwide epidemic and an important risk factor for the development of insulin resistance, type 2 diabetes, nonalcoholic steatohepatitis (NASH), and hepatic cellular carcinoma (HCC). Despite the prevalence of NAFLD, lifestyle interventions involving exercise and weight loss are the only accepted treatments for this disease. Over the last decade, numerous experimental compounds have been shown to improve NAFLD in preclinical animal models, and many of these therapeutics have been shown to increase the activity of the cellular energy sensor AMP-activated protein kinase (A...
Source: AJP: Endocrinology and Metabolism - October 11, 2016 Category: Endocrinology Authors: Smith, B. K., Marcinko, K., Desjardins, E. M., Lally, J. S., Ford, R. J., Steinberg, G. R. Tags: Review Source Type: research
Leucine supplementation stimulates protein synthesis and reduces degradation signal activation in muscle of newborn pigs during acute endotoxemia
In conclusion, parenteral Leu supplementation attenuates the LPS-induced reduction in PS by stimulating mammalian target of rapamycin complex 1-dependent translation and may reduce PD by attenuating autophagy-lysosome and MuRF-1 signaling in neonatal skeletal muscle. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 4, 2016 Category: Endocrinology Authors: Hernandez-Garcia, A. D., Columbus, D. A., Manjarin, R., Nguyen, H. V., Suryawan, A., Orellana, R. A., Davis, T. A. Tags: Articles Source Type: research
25-Hydroxycholesterol impairs endothelial function and vasodilation by uncoupling and inhibiting endothelial nitric oxide synthase
Endothelial dysfunction is a key early step in atherosclerosis. 25-Hydroxycholesterol (25-OHC) is found in atherosclerotic lesions. However, whether 25-OHC promotes atherosclerosis is unclear. Here, we hypothesized that 25-OHC, a proinflammatory lipid, can impair endothelial function, which may play an important role in atherosclerosis. Bovine aortic endothelial cells were incubated with 25-OHC. Endothelial cell proliferation, migration, and tube formation were measured. Nitric oxide (NO) production and superoxide anion generation were determined. The expression and phosphorylation of endothelial NO synthase (eNOS) and Akt...
Source: AJP: Endocrinology and Metabolism - October 4, 2016 Category: Endocrinology Authors: Ou, Z.-J., Chen, J., Dai, W.-P., Liu, X., Yang, Y.-K., Li, Y., Lin, Z.-B., Wang, T.-T., Wu, Y.-Y., Su, D.-H., Cheng, T.-P., Wang, Z.-P., Tao, J., Ou, J.-S. Tags: Articles Source Type: research
Leucine-rich repeat kinase-1 regulates osteoclast function by modulating RAC1/Cdc42 Small GTPase phosphorylation and activation
In this study, we generated a series of Lrrk1 mutants and evaluated their ability to rescue defective bone resorption in Lrrk1-deficient osteoclasts by use of pit formation assays. Overexpression of Lrrk1 or LRR-truncated Lrrk1, but not ANK-truncated Lrrk1, WD40-truncated Lrrk1, Lrrk1-KD, or K651A mutant Lrrk1, rescued bone resorption function of Lrrk1 KO osteoclasts. We next examined whether RAC1/Cdc42 small GTPases are direct substrates of Lrrk1 in osteoclasts. Western blot and pull-down assays revealed that Lrrk1 deficiency in osteoclasts resulted in reduced phosphorylation and activation of RAC1/Cdc42. In vitro kinase ...
Source: AJP: Endocrinology and Metabolism - October 4, 2016 Category: Endocrinology Authors: Zeng, C., Goodluck, H., Qin, X., Liu, B., Mohan, S., Xing, W. Tags: Call for Papers Source Type: research
