Postchallenge hyperglycemia in subjects with low body weight: implication for small glucose volume
In conclusion, postchallenge hyperglycemia in low BW subjects is in part due to small GV rather than impaired glucose metabolism. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - December 6, 2017 Category: Endocrinology Authors: Sakuma, T., Yamashita, K., Miyakoshi, T., Shimodaira, M., Yokota, N., Sato, Y., Hirabayashi, K., Koike, H., Yamauchi, K., Shimbo, T., Aizawa, T. Tags: Research Article Source Type: research

REDD1 induction regulates the skeletal muscle gene expression signature following acute aerobic exercise
The metabolic stress placed on skeletal muscle by aerobic exercise promotes acute and long-term health benefits in part through changes in gene expression. However, the transducers that mediate altered gene expression signatures have not been completely elucidated. Regulated in development and DNA damage 1 (REDD1) is a stress-induced protein whose expression is transiently increased in skeletal muscle following acute aerobic exercise. However, the role of this induction remains unclear. Because REDD1 altered gene expression in other model systems, we sought to determine whether REDD1 induction following acute exercise alte...
Source: AJP: Endocrinology and Metabolism - December 6, 2017 Category: Endocrinology Authors: Gordon, B. S., Steiner, J. L., Rossetti, M. L., Qiao, S., Ellisen, L. W., Govindarajan, S. S., Eroshkin, A. M., Williamson, D. L., Coen, P. M. Tags: Research Article Source Type: research

Brown adipose tissue activation in a rat model of Parkinsons disease
Loss of body weight and fat mass is one of the nonmotor symptoms of Parkinson’s disease (PD). Weight loss is due primarily to reduced energy intake and increased energy expenditure. Whereas inadequate energy intake in PD patients is caused mainly by appetite loss and impaired gastrointestinal absorption, the underlying mechanisms for increased energy expenditure remain largely unknown. Brown adipose tissue (BAT), a key thermogenic tissue in humans and other mammals, plays an important role in thermoregulation and energy metabolism; however, it has not been tested whether BAT is involved in the negative energy balance...
Source: AJP: Endocrinology and Metabolism - December 6, 2017 Category: Endocrinology Authors: Wang, W., Meng, X., Yang, C., Fang, D., Wang, X., An, J., Zhang, J., Wang, L., Lu, T., Ruan, H.-B., Gao, Y. Tags: Research Article Source Type: research

Lipid droplet size and location in human skeletal muscle fibers are associated with insulin sensitivity
In conclusion, the size of individual subsarcolemmal LDs may be involved in the mechanism by which LDs are associated with insulin resistance in skeletal muscle. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Nielsen, J., Christensen, A. E., Nellemann, B., Christensen, B. Tags: Research Article Source Type: research

Oleate activates SREBP-1 signaling activity in SCD1-deficient hepatocytes
Stearoyl-CoA desaturase-1 (SCD1) is a key player in lipid metabolism. SCD1 catalyzes the synthesis of monounsaturated fatty acids (MUFA). MUFA are then incorporated into triacylglycerols and phospholipids. Previous studies have shown that Scd1 deficiency in mice induces metabolic changes in the liver characterized by a decrease in de novo lipogenesis and an increase in β-oxidation. Interestingly, Scd1-deficient mice show a decrease in the expression and maturation of the principal lipogenic transcription factor sterol receptor element binding protein-1 (SREBP-1). The mechanisms mediating this effect on de novo lipogen...
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Lounis, M. A., Bergeron, K.-F., Burhans, M. S., Ntambi, J. M., Mounier, C. Tags: Research Article Source Type: research

Cardiac overexpression of perilipin 2 induces dynamic steatosis: prevention by hormone-sensitive lipase
Cardiac intracellular lipid accumulation (steatosis) is a pathophysiological phenomenon observed in starvation and diabetes mellitus. Perilipin 2 (PLIN2) is a lipid droplet (LD)-associated protein expressed in nonadipose tissues, including the heart. To explore the pathophysiological function of myocardial PLIN2, we generated transgenic (Tg) mice by cardiac-specific overexpression of PLIN2. Tg hearts showed accumulation of numerous small LDs associated with mitochondrial chains and high cardiac triacylglycerol (TAG) content [8-fold greater than wild-type (WT) mice]. Despite massive steatosis, cardiac uptake of glucose, fat...
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Ueno, M., Suzuki, J., Hirose, M., Sato, S., Imagawa, M., Zenimaru, Y., Takahashi, S., Ikuyama, S., Koizumi, T., Konoshita, T., Kraemer, F. B., Ishizuka, T. Tags: Research Article Source Type: research

Anesthesia and bariatric surgery gut preparation alter plasma acylcarnitines reflective of mitochondrial fat and branched-chain amino acid oxidation
The period around bariatric surgery offers a unique opportunity to characterize metabolism responses to dynamic shifts in energy, gut function, and anesthesia. We analyzed plasma acylcarnitines in obese women (n = 17) sampled in the overnight fasted/postabsorptive state approximately 1–2 wk before surgery (condition A), the morning of surgery (prior restriction to a 48-h clear liquid diet coupled in some cases a standard polyethylene glycol gut evacuation: condition B), and following induction of anesthesia (condition C). Comparisons tested if 1) plasma acylcarnitine derivatives reflective of fatty acid oxidation (FA...
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Bhattacharyya, S., Ali, M., Smith, W. H., Minkler, P. E., Stoll, M. S., Hoppel, C. L., Adams, S. H. Tags: Research Article Source Type: research

A novel D2O tracer method to quantify RNA turnover as a biomarker of de novo ribosomal biogenesis, in vitro, in animal models, and in human skeletal muscle
Current methods to quantify in vivo RNA dynamics are limited. Here, we developed a novel stable isotope (D2O) methodology to quantify RNA synthesis (i.e., ribosomal biogenesis) in cells, animal models, and humans. First, proliferating C2C12 cells were incubated in D2O-enriched media and myotubes ±50 ng/ml IGF-I. Second, rat quadriceps (untrained, n = 9; 7-wk interval-"like" training, n = 13) were collected after ~3-wk D2O (70 atom %) administration, with body-water enrichment monitored via blood sampling. Finally, 10 (23 ± 1 yr) men consumed 150-ml D2O followed by 50 ml/wk and undertook 6-wk resistance exerci...
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Brook, M. S., Wilkinson, D. J., Mitchell, W. K., Lund, J. L., Phillips, B. E., Szewczyk, N. J., Kainulainen, H., Lensu, S., Koch, L. G., Britton, S. L., Greenhaff, P. L., Smith, K., Atherton, P. J. Tags: Innovative Methodology Source Type: research

Insulin sensitizer prevents and ameliorates experimental type 1 diabetes
In conclusion, potent insulin sensitizers may counteract genetic predisposition to autoimmune T1D and amplify subtherapeutic insulin into an effective therapeutic measure for the treatment of overt T1D. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Valitsky, M., Hoffman, A., Unterman, T., Bar-Tana, J. Tags: Research Article Source Type: research

Soluble interleukin-13r{alpha}1: a circulating regulator of glucose
Soluble IL-13 receptor-α1, or sIL13rα1, is a soluble protein that binds to interleukin-13 (IL-13) that has been previously described in mice. The function of sIL13rα1 remains unclear, but it has been hypothesized to act as a decoy receptor for IL-13. Recent studies have identified a role for IL-13 in glucose metabolism, suggesting that a decoy receptor for IL-13 might increase circulating glucose levels. Here, we report that delivery of sIL13rα1 to mice by either gene transfer or recombinant protein decreases blood glucose levels. Surprisingly, the glucose-lowering effect of sIL13rα1 was prese...
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Rachmin, I., OMeara, C. C., Ricci-Blair, E. M., Feng, Y., Christensen, E. M., Duffy, J. F., Zitting, K. M., Czeisler, C. A., Pancoast, J. R., Cannon, C. P., ODonoghue, M. L., Morrow, D. A., Lee, R. T. Tags: Research Article Source Type: research

The glucagon-like peptide-1 receptor in the ventromedial hypothalamus reduces short-term food intake in male mice by regulating nutrient sensor activity
Pharmacological activation of the glucagon-like peptide-1 receptor (GLP-1R) in the ventromedial hypothalamus (VMH) reduces food intake. Here, we assessed whether suppression of food intake by GLP-1R agonists (GLP-1RA) in this region is dependent on AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR). We found that pharmacological inhibition of glycolysis, and thus activation of AMPK, in the VMH attenuates the anorectic effect of the GLP-1R agonist exendin-4 (Ex4), indicating that glucose metabolism and inhibition of AMPK are both required for this effect. Furthermore, we found that Ex4-mediated ano...
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Burmeister, M. A., Brown, J. D., Ayala, J. E., Stoffers, D. A., Sandoval, D. A., Seeley, R. J., Ayala, J. E. Tags: Research Article Source Type: research

Increased mitochondrial calcium uniporter in adipocytes underlies mitochondrial alterations associated with insulin resistance
Intracellular calcium influences an array of pathways and affects cellular processes. With the rapidly progressing research investigating the molecular identity and the physiological roles of the mitochondrial calcium uniporter (MCU) complex, we now have the tools to understand the functions of mitochondrial Ca2+ in the regulation of pathophysiological processes. Herein, we describe the role of key MCU complex components in insulin resistance in mouse and human adipose tissue. Adipose tissue gene expression was analyzed from several models of obese and diabetic rodents and in 72 patients with obesity as well as in vitro in...
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Wright, L. E., Vecellio Reane, D., Milan, G., Terrin, A., Di Bello, G., Belligoli, A., Sanna, M., Foletto, M., Favaretto, F., Raffaello, A., Mammucari, C., Nitti, D., Vettor, R., Rizzuto, R. Tags: Research Article Source Type: research

Circulating soluble RAGE isoforms are attenuated in obese, impaired-glucose-tolerant individuals and are associated with the development of type 2 diabetes
The soluble receptor for advanced glycation end products (sRAGE) may be protective against inflammation associated with obesity and type 2 diabetes (T2DM). The aim of this study was to determine the distribution of sRAGE isoforms and whether sRAGE isoforms are associated with risk of T2DM development in subjects spanning the glucose tolerance continuum. In this retrospective analysis, circulating total sRAGE and endogenous secretory RAGE (esRAGE) were quantified via ELISA, and cleaved RAGE (cRAGE) was calculated in 274 individuals stratified by glucose tolerance status (GTS) and obesity. Group differences were probed by AN...
Source: AJP: Endocrinology and Metabolism - December 1, 2017 Category: Endocrinology Authors: Miranda, E. R., Somal, V. S., Mey, J. T., Blackburn, B. K., Wang, E., Farabi, S., Karstoft, K., Fealy, C. E., Kashyap, S., Kirwan, J. P., Quinn, L., Solomon, T. P. J., Haus, J. M. Tags: Research Article Source Type: research

Glycemic control after metabolic surgery: a Granger causality and graph analysis
The purpose of this study was to examine the contribution of nonesterified fatty acids (NEFA) and incretin to insulin resistance and diabetes amelioration after malabsorptive metabolic surgery that induces steatorrhea. In fact, NEFA infusion reduces glucose-stimulated insulin secretion, and high-fat diets predict diabetes development. Six healthy controls, 11 obese subjects, and 10 type 2 diabetic (T2D) subjects were studied before and 1 mo after biliopancreatic diversion (BPD). Twenty-four-hour plasma glucose, NEFA, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) time courses ...
Source: AJP: Endocrinology and Metabolism - November 29, 2017 Category: Endocrinology Authors: Previti, E., Salinari, S., Bertuzzi, A., Capristo, E., Bornstein, S., Mingrone, G. Tags: Research Article Source Type: research

Central effects of insulin detemir on feeding, body weight, and metabolism in rats
Insulin detemir (DET) is a basal insulin analog that, in contrast to other long-acting forms of insulin, has significant weight-gain-sparing effects in diabetic patients. We hypothesized that this effect of DET may be due to its enhanced catabolic action in the central nervous system. We investigated the long-term effects of single third ventricular (3V) microinjections of equimolar doses of DET and regular insulin in normal male rats on feeding, body weight, energy expenditure (EE), and respiratory quotient (RQ). Also, in acute testing, we assessed the ability of lower doses of DET to alter feeding, EE, and RQ when microi...
Source: AJP: Endocrinology and Metabolism - November 29, 2017 Category: Endocrinology Authors: Vasselli, J. R., Pi-Sunyer, F. X., Wall, D. G., John, C. S., Chapman, C. D., Currie, P. J. Tags: Research Article Source Type: research