Is bursting more effective than spiking in evoking pituitary hormone secretion? A spatiotemporal simulation study of calcium and granule dynamics
Endocrine cells of the pituitary gland secrete a number of hormones, and the amount of hormone released by a cell is controlled in large part by the cell's electrical activity and subsequent Ca2+ influx. Typical electrical behaviors of pituitary cells include continuous spiking and so-called pseudo-plateau bursting. It has been shown that the amplitude of Ca2+ fluctuations is greater in bursting cells, leading to the hypothesis that bursting cells release more hormone than spiking cells. In this work, we apply computer simulations to test this hypothesis. We use experimental recordings of electrical activity as input to ma...
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Tagliavini, A., Tabak, J., Bertram, R., Pedersen, M. G. Tags: Articles Source Type: research
Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery
This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Svane, M. S., Bojsen-Moller, K. N., Nielsen, S., Jorgensen, N. B., Dirksen, C., Bendtsen, F., Kristiansen, V. B., Hartmann, B., Holst, J. J., Madsbad, S. Tags: Articles Source Type: research
Neuregulin-1 attenuates development of nephropathy in a type 1 diabetes mouse model with high cardiovascular risk
In conclusion, systemic administration of rhNRG-1 in hypercholesterolemic type 1 diabetic mice simultaneously protects against complications in the heart, arteries and kidneys. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Vandekerckhove, L., Vermeulen, Z., Liu, Z. Z., Boimvaser, S., Patzak, A., Segers, V. F. M., De Keulenaer, G. W. Tags: Articles Source Type: research
Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity
The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) ...
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Patterson, R. E., Kalavalapalli, S., Williams, C. M., Nautiyal, M., Mathew, J. T., Martinez, J., Reinhard, M. K., McDougall, D. J., Rocca, J. R., Yost, R. A., Cusi, K., Garrett, T. J., Sunny, N. E. Tags: Call for Papers Source Type: research
Diabetic cardiomyopathy: role of the E3 ubiquitin ligase
Diabetic cardiomyopathy (DCM) is the leading cause of mortality in diabetes. As the number of cases of diabetes continues to rise, it is urgent to develop new strategies to protect against DCM, which is characterized by cardiac hypertrophy, increased apoptosis, fibrosis, and altered insulin metabolism. The E3 ubiquitin ligases (E3s), one component of the ubiquitin-proteasome system, play vital roles in all of the features of DCM listed above. They also modulate the activity of several transcription factors involved in the pathogenesis of DCM. In addition, the E3s degrade both insulin receptor and insulin receptor substrate...
Source: AJP: Endocrinology and Metabolism - March 31, 2016 Category: Endocrinology Authors: Bai, T., Wang, F., Mellen, N., Zheng, Y., Cai, L. Tags: Review Source Type: research
AMPK{gamma}3 is dispensable for skeletal muscle hypertrophy induced by functional overload
In conclusion, our functional, transcriptional, and signaling data provide evidence against the involvement of the AMPK3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPK3 isoform is dispensable for functional overload-induced muscle growth. Mechanical loading can override signaling pathways that act as negative effectors of mTOR signaling and consequently promote skeletal muscle hypertrophy. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - March 15, 2016 Category: Endocrinology Authors: Riedl, I., Osler, M. E., Björnholm, M., Egan, B., Nader, G. A., Chibalin, A. V., Zierath, J. R. Tags: Articles Source Type: research
Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer
Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[18F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([11C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m–2·min–1) to 3-h saline in...
Source: AJP: Endocrinology and Metabolism - March 15, 2016 Category: Endocrinology Authors: Mather, K. J., Hutchins, G. D., Perry, K., Territo, W., Chisholm, R., Acton, A., Glick-Wilson, B., Considine, R. V., Moberly, S., DeGrado, T. R. Tags: Articles Source Type: research
Neuregulin improves response to glucose tolerance test in control and diabetic rats
Neuregulin (NRG) is an EGF-related growth factor that binds to the tyrosine kinase receptors ErbB3 and ErbB4, thus inducing tissue development and muscle glucose utilization during contraction. Here, we analyzed whether NRG has systemic effects regulating glycemia in control and type 2 diabetic rats. To this end, recombinant NRG (rNRG) was injected into Zucker diabetic fatty (ZDF) rats and their respective lean littermates 15 min before a glucose tolerance test (GTT) was performed. rNRG enhanced glucose tolerance without promoting the activation of the insulin receptor (IR) or insulin receptor substrates (IRS) in muscle an...
Source: AJP: Endocrinology and Metabolism - March 15, 2016 Category: Endocrinology Authors: Lopez-Soldado, I., Niisuke, K., Veiga, C., Adrover, A., Manzano, A., Martinez-Redondo, V., Camps, M., Bartrons, R., Zorzano, A., Guma, A. Tags: Articles Source Type: research
Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD
nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model...
Source: AJP: Endocrinology and Metabolism - March 15, 2016 Category: Endocrinology Authors: Luo, Y., Burrington, C. M., Graff, E. C., Zhang, J., Judd, R. L., Suksaranjit, P., Kaewpoowat, Q., Davenport, S. K., O'Neill, A. M., Greene, M. W. Tags: Articles Source Type: research
Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats
Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynami...
Source: AJP: Endocrinology and Metabolism - March 15, 2016 Category: Endocrinology Authors: Shankaran, M., Shearer, T. W., Stimpson, S. A., Turner, S. M., King, C., Wong, P.-y. A., Shen, Y., Turnbull, P. S., Kramer, F., Clifton, L., Russell, A., Hellerstein, M. K., Evans, W. J. Tags: Translational Physiology Source Type: research
Thymoquinone, a bioactive component of Nigella sativa, normalizes insulin secretion from pancreatic {beta}-cells under glucose overload via regulation of malonyl-CoA
Thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) is a major bioactive component of Nigella sativa, a plant used in traditional medicine to treat a variety of symptoms, including elevated blood glucose levels in type 2 diabetic patients. Normalization of elevated blood glucose depends on both glucose disposal by peripheral tissues and glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. We employed clonal β-cells and rodent islets to investigate the effects of thymoquinone (TQ) and Nigella sativa extracts (NSEs) on GSIS and cataplerotic metabolic pathways implicated in the regulation of GSIS. T...
Source: AJP: Endocrinology and Metabolism - March 15, 2016 Category: Endocrinology Authors: Gray, J. P., Zayasbazan Burgos, D., Yuan, T., Seeram, N., Rebar, R., Follmer, R., Heart, E. A. Tags: Call for Papers Source Type: research
Methionine sulfoxide reductase A affects {beta}-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease
Accumulation of oxidized proteins, and especially β-amyloid (Aβ), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aβ through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aβ in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aβ. Indeed, the novel MsrA-deficient APP mice...
Source: AJP: Endocrinology and Metabolism - March 15, 2016 Category: Endocrinology Authors: Moskovitz, J., Du, F., Bowman, C. F., Yan, S. S. Tags: Call for Papers Source Type: research
Muscle microvasculature's structural and functional specializations facilitate muscle metabolism
We review the evolving findings from studies that examine the relationship between the structural and functional properties of skeletal muscle's vasculature and muscle metabolism. Unique aspects of the organization of the muscle microvasculature are highlighted. We discuss the role of vasomotion at the microscopic level and of flowmotion at the tissue level as modulators of perfusion distribution in muscle. We then consider in some detail how insulin and exercise each modulate muscle perfusion at both the microvascular and whole tissue level. The central role of the vascular endothelial cell in modulating both perfusion an...
Source: AJP: Endocrinology and Metabolism - March 15, 2016 Category: Endocrinology Authors: Kusters, Y. H. A. M., Barrett, E. J. Tags: Review Source Type: research
Fate of orally administered radioactive fatty acids in the late-pregnant rat
To investigate the biodisponibility of placental transfer of fatty acids, rats pregnant for 20 days were given tracer amounts of [14C]palmitic (PA), oleic (OA), linoleic (LA), α-linolenic (LNA), or docosahexaenoic acid (DHA) orally and euthanized at 0.5, 1.0, 2.0, or 8.0 h thereafter. Maternal plasma radioactivity in lipids initially increased only to decline at later times. Most of the label appeared first as triacylglycerols (TAG); later, the proportion in phospholipids (PhL) increased. The percentage of label in placental lipids was also always highest shortly after administration and declined later; again, PhL in...
Source: AJP: Endocrinology and Metabolism - March 1, 2016 Category: Endocrinology Authors: Lopez-Luna, P., Ortega-Senovilla, H., Lopez-Soldado, I., Herrera, E. Tags: Articles Source Type: research
Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells
Advanced glycation end products (AGEs) disturb bone remodeling during aging, and this process is accelerated in diabetes. However, their role in modulation of osteoclast-induced bone resorption is controversial, with some studies indicating that AGEs enhance bone resorption and others showing the opposite effect. We determined whether AGEs present at different stages of osteoclast differentiation affect bone resorption differently. Based on increased levels of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK), we identified day 4 of induction as the dividing time of cell fusion stage and mature stage in RAW...
Source: AJP: Endocrinology and Metabolism - March 1, 2016 Category: Endocrinology Authors: Li, Z., Li, C., Zhou, Y., Chen, W., Luo, G., Zhang, Z., Wang, H., Zhang, Y., Xu, D., Sheng, P. Tags: Articles Source Type: research
