Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity
Sweet taste receptors (STRs) on the tongue mediate gustatory sweet sensing, but their expression in the gut, pancreas, and adipose tissue suggests a physiological contribution to whole body nutrient sensing and metabolism. However, little is known about the function and contribution of these sugar sensors during metabolic stress induced by overnutrition and subsequent obesity. Here, we investigated the effects of high-fat/low-carbohydrate (HF/LC) diet on glucose homeostasis and energy balance in mice with global disruption of the sweet taste receptor protein T1R2. We assessed body composition, energy balance, glucose homeo...
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Smith, K. R., Hussain, T., Karimian Azari, E., Steiner, J. L., Ayala, J. E., Pratley, R. E., Kyriazis, G. A. Tags: Articles Source Type: research
Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice
This report suggests that inflammation induced by infiltrated M could cause not only insulin resistance but also reduction of energy expenditure in adipose tissues. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Sakamoto, T., Nitta, T., Maruno, K., Yeh, Y.-S., Kuwata, H., Tomita, K., Goto, T., Takahashi, N., Kawada, T. Tags: Articles Source Type: research
Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet
Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion, pancreatic β-cell proliferation, and adiponectin expression in adipocytes. Previously, we showed that long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level, improved glucose tolerance, and increased the fasting serum insulin concentration as well as pancreatic β-cell area in female mice fed a normal or high-fat, high-sucrose diet. We have now performed similar experiments with male mice and found that such GluOC administration induced glucose into...
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Yasutake, Y., Mizokami, A., Kawakubo-Yasukochi, T., Chishaki, S., Takahashi, I., Takeuchi, H., Hirata, M. Tags: Articles Source Type: research
Ribosome biogenesis may augment resistance training-induced myofiber hypertrophy and is required for myotube growth in vitro
Resistance exercise training (RT) is the most effective method for increasing skeletal muscle mass in older adults; however, the amount of RT-induced muscle growth is highly variable between individuals. Recent evidence from our laboratory and others suggests ribosome biogenesis may be an important factor regulating RT-induced hypertrophy, and we hypothesized that the extent of hypertrophy is at least partly regulated by the amount of RT-induced ribosome biogenesis. To examine this, 42 older adults underwent 4 wk of RT aimed at inducing hypertrophy of the knee extensors (e.g., 2 sets of squat, leg press, and knee extension...
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Stec, M. J., Kelly, N. A., Many, G. M., Windham, S. T., Tuggle, S. C., Bamman, M. M. Tags: Articles Source Type: research
Targeting the ERK signaling pathway as a potential treatment for insulin resistance and type 2 diabetes
Extracellular signal-regulated kinase (ERK) has been implicated in the development of insulin resistance associated with obesity and type 2 diabetes mellitus. We have now examined the potential of pharmacological targeting of the ERK pathway with MEK (ERK kinase) inhibitors (PD184352 and PD0325901) for the treatment of obesity-associated insulin resistance. The effects of PD184352 and PD0325901 on the expression of adipocytokines and lipolysis activity were thus examined in 3T3-L1 adipocytes maintained in long-term culture as a model of adipocyte hypertrophy. Leptin receptor-deficient (db/db) mice and high-fat diet-fed KKA...
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Ozaki, K.-i., Awazu, M., Tamiya, M., Iwasaki, Y., Harada, A., Kugisaki, S., Tanimura, S., Kohno, M. Tags: Articles Source Type: research
Regulation of metabolism: the work-to-rest transition in skeletal muscle
The behavior of oxidative phosphorylation predicted by a model for the mechanism and kinetics of cytochrome c oxidase is compared with the experimentally observed behavior during the work-to-rest transition in skeletal muscle. For both experiment and model, when work stops, the increase in creatine phosphate and decrease in creatine and inorganic phosphate concentrations ([CrP], [Cr], and [Pi]) begin immediately. The rate of change for each is maximal and then progressively slows as the increasing energy state ([ATP]/[ADP][Pi]) suppresses the rate of oxidative phosphorylation. The time courses can be reasonably fitted to s...
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Wilson, D. F. Tags: Articles Source Type: research
Changes in one-carbon metabolism after duodenal-jejunal bypass surgery
This study shows that bariatric surgery altered trans-sulfuration and purine metabolism in the liver. Characterization of these mechanisms increases our understanding of the benefits of bariatric surgery. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Jung, J., Ha, T. K., Lee, J., Lho, Y., Nam, M., Lee, D., le Roux, C. W., Ryu, D. H., Ha, E., Hwang, G.-S. Tags: Articles Source Type: research
Direct regulation of IGF-binding protein 1 promoter by interleukin-1{beta} via an insulin- and FoxO-1-independent mechanism
The level of insulin-like growth factor-binding protein 1 (IGFBP1), a liver-produced serum protein that regulates insulin-like growth factor-I bioactivity, glucose homeostasis, and tissue regeneration, increases during inflammation. This manuscript describes a novel pathway for the regulation of hepatic IGFBP1 mRNA and protein levels by interleukin (IL)-1β. Experiments with the luciferase reporter system show that IL-1β stimulates transcriptional activity from the 1-kb promoter region of IGFBP1. Although IL-1β stimulation suppresses the insulin activation of protein kinase B, the major upstream regulator of ...
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Shi, L., Banerjee, D., Dobierzewska, A., Sathishkumar, S., Karakashian, A. A., Giltiay, N. V., Nikolova-Karakashian, M. N. Tags: Call for Papers Source Type: research
Paracrine regulation of glucagon secretion: the {beta}/{alpha}/{delta} model
The regulation of glucagon secretion in the pancreatic α-cell is not well understood. It has been proposed that glucose suppresses glucagon secretion either directly through an intrinsic mechanism within the α-cell or indirectly through an extrinsic mechanism. Previously, we described a mathematical model for isolated pancreatic α-cells and used it to investigate possible intrinsic mechanisms of regulating glucagon secretion. We demonstrated that glucose can suppress glucagon secretion through both ATP-dependent potassium channels (KATP) and a store-operated current (SOC). We have now developed an islet m...
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Watts, M., Ha, J., Kimchi, O., Sherman, A. Tags: Call for Papers Source Type: research
Regulation of cardiomyocyte autophagy by calcium
Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle...
Source: AJP: Endocrinology and Metabolism - April 14, 2016 Category: Endocrinology Authors: Shaikh, S., Troncoso, R., Criollo, A., Bravo-Sagua, R., Garcia, L., Morselli, E., Cifuentes, M., Quest, A. F. G., Hill, J. A., Lavandero, S. Tags: Review Source Type: research
Transcriptional regulation of FoxO3 gene by glucocorticoids in murine myotubes
Glucocorticoids and FoxO3 exert similar metabolic effects in skeletal muscle. FoxO3 gene expression was increased by dexamethasone (Dex), a synthetic glucocorticoid, both in vitro and in vivo. In C2C12 myotubes the increased expression is due to, at least in part, the elevated rate of FoxO3 gene transcription. In the mouse FoxO3 gene, we identified three glucocorticoid receptor (GR) binding regions (GBRs): one being upstream of the transcription start site, –17kbGBR; and two in introns, +45kbGBR and +71kbGBR. Together, these three GBRs contain four 15-bp glucocorticoid response elements (GREs). Micrococcal nuclease (...
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Kuo, T., Liu, P. H., Chen, T.-C., Lee, R. A., New, J., Zhang, D., Lei, C., Chau, A., Tang, Y., Cheung, E., Wang, J.-C. Tags: Articles Source Type: research
Gastrin decreases Na+,K+-ATPase activity via a PI 3-kinase- and PKC-dependent pathway in human renal proximal tubule cells
In this study, we show that gastrin induced the phosphorylation of human Na+,K+-ATPase at serine 16, resulting in its endocytosis via Rab5 and Rab7 endosomes. The gastrin-stimulated phosphorylation of Na+,K+-ATPase was dependent on PI 3-kinase because the phosphorylation was blocked by the PI 3-kinase inhibitor wortmannin. The phosphorylation of Na+,K+-ATPase was also blocked by chelerythrine, a pan-PKC inhibitor, Gö-6976, a conventional PKC (cPKC) inhibitor, and BAPTA-AM, an intracellular calcium chelator, suggesting the importance of cPKC and intracellular calcium in the gastrin signaling pathway. The gastrin-med...
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Liu, T., Konkalmatt, P. R., Yang, Y., Jose, P. A. Tags: Articles Source Type: research
Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes
This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [14C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epi...
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Burgeiro, A., Fuhrmann, A., Cherian, S., Espinoza, D., Jarak, I., Carvalho, R. A., Loureiro, M., Patricio, M., Antunes, M., Carvalho, E. Tags: Articles Source Type: research
Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo
Because it leads to a rapid and massive muscle hypertrophy, postnatal blockade of the activin type IIB receptor (ActRIIB) is a promising therapeutic strategy for counteracting muscle wasting. However, the functional consequences remain very poorly documented in vivo. Here, we have investigated the impact of 8-wk ActRIIB blockade with soluble receptor (sActRIIB-Fc) on gastrocnemius muscle anatomy, energy metabolism, and force-generating capacity in wild-type mice, using totally noninvasive magnetic resonance imaging (MRI) and dynamic 31P-MRS. Compared with vehicle (PBS) control, sActRIIB-Fc treatment resulted in a dramatic ...
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Bechir, N., Pecchi, E., Relizani, K., Vilmen, C., Le Fur, Y., Bernard, M., Amthor, H., Bendahan, D., Giannesini, B. Tags: Articles Source Type: research
Effects of dietary phosphate on glucose and lipid metabolism
In this study, we investigated the effects of dietary Pi on glucose and lipid metabolism in healthy rats. Male 8-wk-old Sprague-Dawley rats were divided into three groups and given experimental diets containing varying amounts of Pi, i.e., 0.2 [low Pi (LP)], 0.6 [control Pi (CP)], and 1.2% [high Pi (HP)]. After 4 wk, the HP group showed lower visceral fat accumulation compared with other groups, accompanied by a low respiratory exchange ratio (Vco2/Vo2) without alteration of locomotive activity. The HP group had lower levels of plasma insulin and nonesterified fatty acids. In addition, the HP group also showed suppressed e...
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Abuduli, M., Ohminami, H., Otani, T., Kubo, H., Ueda, H., Kawai, Y., Masuda, M., Yamanaka-Okumura, H., Sakaue, H., Yamamoto, H., Takeda, E., Taketani, Y. Tags: Articles Source Type: research
