Cortical bone loss caused by glucocorticoid excess requires RANKL production by osteocytes and is associated with reduced OPG expression in mice
Glucocorticoid excess is a major cause of low bone mass and fractures. Glucocorticoid administration decreases cortical thickness and increases cortical porosity in mice, and these changes are associated with increased osteoclast number at the endocortical surface. Receptor activator of NF-B ligand (RANKL) produced by osteocytes is required for osteoclast formation in cancellous bone as well as the increase in cortical bone resorption caused by mechanical unloading or dietary calcium deficiency. However, whether osteocyte-derived RANKL also participates in the increase in bone resorption caused by glucocorticoid excess is ...
Source: AJP: Endocrinology and Metabolism - August 31, 2016 Category: Endocrinology Authors: Piemontese, M., Xiong, J., Fujiwara, Y., Thostenson, J. D., O'Brien, C. A. Tags: Articles Source Type: research
Pregnancy-induced changes in the circadian expression of hepatic clock genes: implications for maternal glucose homeostasis
Adaptations in maternal carbohydrate metabolism are particularly important in pregnancy because glucose is the principal energy substrate used by the fetus. As metabolic homeostasis is intricately linked to the circadian system via the rhythmic expression of clock genes, it is likely that metabolic adaptations during pregnancy also involve shifts in maternal circadian function. We hypothesized that maternal adaptation in pregnancy involves changes in the hepatic expression of clock genes, which drive downstream shifts in circadian expression of glucoregulatory genes. Maternal liver and plasma (n = 6–8/group) were col...
Source: AJP: Endocrinology and Metabolism - August 31, 2016 Category: Endocrinology Authors: Wharfe, M. D., Wyrwoll, C. S., Waddell, B. J., Mark, P. J. Tags: Articles Source Type: research
Connective tissue growth factor is critical for proper {beta}-cell function and pregnancy-induced {beta}-cell hyperplasia in adult mice
During pregnancy, maternal β-cells undergo compensatory changes, including increased β-cell mass and enhanced glucose-stimulated insulin secretion. Failure of these adaptations to occur results in gestational diabetes mellitus. The secreted protein connective tissue growth factor (CTGF) is critical for normal β-cell development and promotes regeneration after partial β-cell ablation. During embryogenesis, CTGF is expressed in pancreatic ducts, vasculature, and β-cells. In adult pancreas, CTGF is expressed only in the vasculature. Here we show that pregnant mice with global Ctgf haploinsufficiency (...
Source: AJP: Endocrinology and Metabolism - August 31, 2016 Category: Endocrinology Authors: Pasek, R. C., Dunn, J. C., Elsakr, J. M., Aramandla, M., Matta, A. R., Gannon, M. Tags: Call for Papers Source Type: research
{beta}-Cell dedifferentiation, reduced duct cell plasticity, and impaired {beta}-cell mass regeneration in middle-aged rats
Limitations in β-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated β-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. β-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, β-cell mass did not change after Px or after gastrin treatment in middle-aged rats. β-Cell replic...
Source: AJP: Endocrinology and Metabolism - August 31, 2016 Category: Endocrinology Authors: Tellez, N., Vilaseca, M., Marti, Y., Pla, A., Montanya, E. Tags: Call for Papers Source Type: research
Liver glycogen metabolism during and after prolonged endurance-type exercise
Carbohydrate and fat are the main substrates utilized during prolonged endurance-type exercise. The relative contribution of each is determined primarily by the intensity and duration of exercise, along with individual training and nutritional status. During moderate- to high-intensity exercise, carbohydrate represents the main substrate source. Because endogenous carbohydrate stores (primarily in liver and muscle) are relatively small, endurance-type exercise performance/capacity is often limited by endogenous carbohydrate availability. Much exercise metabolism research to date has focused on muscle glycogen utilization, ...
Source: AJP: Endocrinology and Metabolism - August 31, 2016 Category: Endocrinology Authors: Gonzalez, J. T., Fuchs, C. J., Betts, J. A., van Loon, L. J. C. Tags: Review Source Type: research
Irisin exerts dual effects on browning and adipogenesis of human white adipocytes
To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK...
Source: AJP: Endocrinology and Metabolism - August 18, 2016 Category: Endocrinology Authors: Zhang, Y., Xie, C., Wang, H., Foss, R. M., Clare, M., George, E. V., Li, S., Katz, A., Cheng, H., Ding, Y., Tang, D., Reeves, W. H., Yang, L.-J. Tags: Articles Source Type: research
Defining human insulin-like growth factor I gene regulation
Growth hormone (GH) plays an essential role in controlling somatic growth and in regulating multiple physiological processes in humans and other species. Insulin-like growth factor I (IGF-I), a conserved, secreted 70-amino acid peptide, is a critical mediator of many of the biological effects of GH. Previous studies have demonstrated that GH rapidly and potently promotes IGF-I gene expression in rodents and in some other mammals through the transcription factor STAT5b, leading to accumulation of IGF-I mRNAs and production of IGF-I. Despite this progress, very little is known about how GH or other trophic factors control hu...
Source: AJP: Endocrinology and Metabolism - August 18, 2016 Category: Endocrinology Authors: Mukherjee, A., Alzhanov, D., Rotwein, P. Tags: Articles Source Type: research
Short-term and long-term effects of submaximal maternal exercise on offspring glucose homeostasis and pancreatic function
Only a few studies have explored the effects of maternal exercise during gestation on adult offspring metabolism. We set out to test whether maternal controlled submaximal exercise maintained troughout all gestational periods induces persistant metabolic changes in the offspring. We used a model of 15-wk-old nulliparous female Wistar rats that exercised (trained group) before and during gestation at a submaximal intensity or remained sedentary (control group). At weaning, male offspring from trained dams showed reduced basal glycemia (119.7 ± 2.4 vs. 130.5 ± 4.1 mg/dl, P < 0.05), pancreas relative weight (...
Source: AJP: Endocrinology and Metabolism - August 18, 2016 Category: Endocrinology Authors: Quiclet, C., Siti, F., Dubouchaud, H., Vial, G., Berthon, P., Fontaine, E., Batandier, C., Couturier, K. Tags: Call for Papers Source Type: research
Changes in the expression of the type 2 diabetes-associated gene VPS13C in the {beta}-cell are associated with glucose intolerance in humans and mice
Single nucleotide polymorphisms (SNPs) close to the VPS13C, C2CD4A and C2CD4B genes on chromosome 15q are associated with impaired fasting glucose and increased risk of type 2 diabetes. eQTL analysis revealed an association between possession of risk (C) alleles at a previously implicated causal SNP, rs7163757, and lowered VPS13C and C2CD4A levels in islets from female (n = 40, P < 0.041) but not from male subjects. Explored using promoter-reporter assays in β-cells and other cell lines, the risk variant at rs7163757 lowered enhancer activity. Mice deleted for Vps13c selectively in the β-cell were generated by...
Source: AJP: Endocrinology and Metabolism - August 18, 2016 Category: Endocrinology Authors: Mehta, Z. B., Fine, N., Pullen, T. J., Cane, M. C., Hu, M., Chabosseau, P., Meur, G., Velayos-Baeza, A., Monaco, A. P., Marselli, L., Marchetti, P., Rutter, G. A. Tags: Call for Papers Source Type: research
Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments
Exercising women with menstrual disturbances frequently display a low resting metabolic rate (RMR) when RMR is expressed relative to body size or lean mass. However, normalizing RMR for body size or lean mass does not account for potential differences in the size of tissue compartments with varying metabolic activities. To explore whether the apparent RMR suppression in women with exercise-associated amenorrhea is a consequence of a lower proportion of highly active metabolic tissue compartments or the result of metabolic adaptations related to energy conservation at the tissue level, RMR and metabolic tissue compartments ...
Source: AJP: Endocrinology and Metabolism - August 7, 2016 Category: Endocrinology Authors: Koehler, K., Williams, N. I., Mallinson, R. J., Southmayd, E. A., Allaway, H. C. M., De Souza, M. J. Tags: Articles Source Type: research
Novel insights into development of diabetic bladder disorder provided by metabolomic analysis of the rat nondiabetic and diabetic detrusor and urothelial layer
There are at present no published studies providing a global overview of changes in bladder metabolism resulting from diabetes. Such studies have the potential to provide mechanistic insight into the development of diabetic bladder disorder (DBD). In the present study, we compared the metabolome of detrusor and urothelial layer in a 1-mo streptozotocin-induced rat model of type 1 diabetes with nondiabetic controls. Our studies revealed that diabetes caused both common and differential changes in the detrusor and urothelial layer's metabolome. Diabetes resulted in similar changes in the levels of previously described diabet...
Source: AJP: Endocrinology and Metabolism - August 7, 2016 Category: Endocrinology Authors: Wang, Y., Deng, G. G., Davies, K. P. Tags: Articles Source Type: research
Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents
Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1–3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed. Here, we show that imeglimin directly activa...
Source: AJP: Endocrinology and Metabolism - August 7, 2016 Category: Endocrinology Authors: Perry, R. J., Cardone, R. L., Petersen, M. C., Zhang, D., Fouqueray, P., Hallakou-Bozec, S., Bolze, S., Shulman, G. I., Petersen, K. F., Kibbey, R. G. Tags: Call for Papers Source Type: research
Posttranslational modifications and dysfunction of mitochondrial enzymes in human heart failure
Deficiency of energy supply is a major complication contributing to the syndrome of heart failure (HF). Because the concurrent activity profile of mitochondrial bioenergetic enzymes has not been studied collectively in human HF, our aim was to examine the mitochondrial enzyme defects in left ventricular myocardium obtained from explanted end-stage failing hearts. Compared with nonfailing donor hearts, activity rates of complexes I and IV and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase, and aconitase were lower in HF, as determined spectrophotometrically. However, activity rates of complexes II an...
Source: AJP: Endocrinology and Metabolism - August 7, 2016 Category: Endocrinology Authors: Sheeran, F. L., Pepe, S. Tags: Call for Papers Source Type: research
Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma
Burn trauma results in prolonged hypermetabolism and skeletal muscle wasting. How hypermetabolism contributes to muscle wasting in burn patients remains unknown. We hypothesized that oxidative stress, cytosolic protein degradation, and mitochondrial stress as a result of hypermetabolism contribute to muscle cachexia postburn. Patients (n = 14) with burns covering >30% of their total body surface area were studied. Controls (n = 13) were young healthy adults. We found that burn patients were profoundly hypermetabolic at both the skeletal muscle and systemic levels, indicating increased oxygen consumption by mitochondria....
Source: AJP: Endocrinology and Metabolism - August 7, 2016 Category: Endocrinology Authors: Ogunbileje, J. O., Porter, C., Herndon, D. N., Chao, T., Abdelrahman, D. R., Papadimitriou, A., Chondronikola, M., Zimmers, T. A., Reidy, P. T., Rasmussen, B. B., Sidossis, L. S. Tags: Call for Papers Source Type: research
Targeting ceramide metabolism in obesity
Obesity is a major health concern that increases the risk for insulin resistance, type 2 diabetes (T2D), and cardiovascular disease. Thus, an enormous research effort has been invested into understanding how obesity-associated dyslipidemia and obesity-induced alterations in lipid metabolism increase the risk for these diseases. Accordingly, it has been proposed that the accumulation of lipid metabolites in organs such as the liver, skeletal muscle, and heart is critical to these obesity-induced pathologies. Ceramide is one such lipid metabolite that accumulates in tissues in response to obesity, and both pharmacological an...
Source: AJP: Endocrinology and Metabolism - August 7, 2016 Category: Endocrinology Authors: Aburasayn, H., Al Batran, R., Ussher, J. R. Tags: Reviews Source Type: research
