Control of hyperglycemia in male mice by leflunomide: mechanisms of action
p70 S6 kinase (S6K1) is a serine/threonine kinase that phosphorylates the insulin receptor substrate-1 (IRS-1) at serine 1101 and desensitizes insulin receptor signaling. S6K1 hyperactivation due to overnutrition leads to hyperglycemia and type 2 diabetes. Our recent study showed that A77 1726, the active metabolite of the anti-rheumatoid arthritis (RA) drug leflunomide, is an inhibitor of S6K1. Whether leflunomide can control hyperglycemia and sensitize the insulin receptor has not been tested. Here we report that A77 1726 increased AKTS473/T308 and S6K1T389 phosphorylation but decreased S6S235/236 and IRS-1S1101 phosphor...
Source: Journal of Endocrinology - March 1, 2018 Category: Endocrinology Authors: Chen, J., Sun, J., Doscas, M. E., Ye, J., Williamson, A. J., Li, Y., Li, Y., Prinz, R. A., Xu, X. Tags: Research Source Type: research
Thyroid hormone receptor localization in target tissues
The thyroid hormone receptors, TRα1, TRβ1 and other subtypes, are members of the nuclear receptor superfamily that mediate the action of thyroid hormone signaling in numerous tissues to regulate important physiological and developmental processes. Their most well-characterized role is as ligand-dependent transcription factors; TRs bind thyroid hormone response elements in the presence or absence of thyroid hormone to facilitate the expression of target genes. Although primarily residing in the nucleus, TRα1 and TRβ1 shuttle rapidly between the nucleus and cytoplasm. We have identified multiple nuclear...
Source: Journal of Endocrinology - March 1, 2018 Category: Endocrinology Authors: Anyetei-Anum, C. S., Roggero, V. R., Allison, L. A. Tags: Review Source Type: research
Prebiotic prevents impaired kidney and renal Oat3 functions in obese rats
This study aimed to investigate the effects of xylooligosaccharide (XOS) on renal function, renal organic anion transporter 3 (Oat3) and the mechanisms involved. High-fat diet was provided for 12 weeks in male Wistar rats. After that, the rats were divided into normal diet (ND); normal diet treated with XOS (NDX); high-fat diet (HF) and high-fat diet treated with XOS (HFX). XOS was given daily at a dose of 1000 mg for 12 weeks. At week 24, HF rats showed a significant increase in obesity and insulin resistance associated with podocyte injury, increased microalbuminuria, decreased creatinine clearance and impaired Oat3 func...
Source: Journal of Endocrinology - February 26, 2018 Category: Endocrinology Authors: Wanchai, K., Yasom, S., Tunapong, W., Chunchai, T., Thiennimitr, P., Chaiyasut, C., Pongchaidecha, A., Chatsudthipong, V., Chattipakorn, S., Chattipakorn, N., Lungaphin, A. Tags: Research Source Type: research
The androgen receptor in bone marrow progenitor cells negatively regulates fat mass
In conclusion, these data provide the first evidence for an action of androgens via the AR in mesenchymal bone marrow PCs to negatively regulate fat mass and improve metabolic function. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - February 26, 2018 Category: Endocrinology Authors: Russell, P. K., Mangiafico, S., Fam, B. C., Clarke, M. V., Marin, E. S., Andrikopoulos, S., Wiren, K. M., Zajac, J. D., Davey, R. A. Tags: Research Source Type: research
Gut as an emerging organ for the treatment of diabetes: focus on mechanism of action of bariatric and endoscopic interventions
Increasing worldwide prevalence of type 2 diabetes mellitus and its accompanying pathologies such as obesity, arterial hypertension and dyslipidemia represents one of the most important challenges of current medicine. Despite intensive efforts, high percentage of patients with type 2 diabetes does not achieve treatment goals and struggle with increasing body weight and poor glucose control. While novel classes of antidiabetic medications such as incretin-based therapies and gliflozins have some favorable characteristics compared to older antidiabetics, the only therapeutic option shown to substantially modify the progressi...
Source: Journal of Endocrinology - February 22, 2018 Category: Endocrinology Authors: Haluzik, M., Kratochvilova, H., Haluzikova, D., Mraz, M. Tags: Review Source Type: research
SRT2104 attenuates diabetes-induced aortic endothelial dysfunction via inhibition of P53
Endothelial dysfunction contributes to diabetic macrovascular complications. Sirtuin 1 (SIRT1) protects against diabetic vasculopathy. SRT2104 is a novel SIRT1 activator and was not previously studied for its effects on diabetes-induced aortic endothelial dysfunction. Additionally, whether or to what extent deacetylation of P53, a substrate of SIRT1, is required for the effects of SIRT1 activation was unclear, given the fact that SIRT1 has multiple targets. Moreover, little was known about the pathogenic role of P53 in diabetes-induced aortic injury. To these ends, diabetes was induced by streptozotocin in C57BL/6 mice. Th...
Source: Journal of Endocrinology - February 21, 2018 Category: Endocrinology Authors: Wu, H., Wu, J., Zhou, S., Huang, W., Li, Y., Zhang, H., Wang, J., Jia, Y. Tags: Research Source Type: research
CRABP1 protects the heart from isoproterenol-induced acute and chronic remodeling
This study demonstrates increased susceptibility of CKO mice to ISO-induced acute and chronic cardiac injury due to, at least in part, elevated CaMKII activity. Deleting Crabp1 results in reduced baseline cardiac function and aggravated damage challenged with acute and persistent β-adrenergic stimulation. This is the first report of a physiological role of CRABP1 as an endogenous regulator of CaMKII, which protects the heart from ISO-induced damage. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - February 15, 2018 Category: Endocrinology Authors: Park, S. W., Persaud, S. D., Ogokeh, S., Meyers, T. A., Townsend, D., Wei, L.-N. Tags: Research Source Type: research
Physiological and pathological implications of retinoid action in the endometrium
The objectives are to identify limitations in current knowledge regarding the molecular actions of retinoids in endometrial biology and to stimulate new investigations toward the development potential therapeutics to ameliorate or prevent endometriosis symptoms. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - February 8, 2018 Category: Endocrinology Authors: Jiang, Y., Chen, L., Taylor, R. N., Li, C., Zhou, X. Tags: Review Source Type: research
Cholecystokinin is involved in triglyceride fatty acid uptake by rat adipose tissue
We report that administration of CCK-8 (a bioactive fragment of CCK) to rats: (i) reduces plasma ANGTPL-4 levels; (ii) represses Angptl-4 expression in WAT and (iii) simultaneously enhances LPL activity in this tissue without inducing Lpl expression. In vivo CCK-8 effects are specifically antagonized by the CCK-2 receptor (CCK-2R) antagonist, L-365,260. Moreover, CCK-8 downregulates Angptl-4 expression in wild-type pre-adipocytes, an effect that is not observed in engineered pre-adipocytes lacking CCK-2R. These effects have functional consequences as CCK-8 was found to promote the uptake of dietary fatty acids by WAT, as d...
Source: Journal of Endocrinology - February 8, 2018 Category: Endocrinology Authors: Plaza, A., Merino, B., Cano, V., Dominguez, G., Perez-Castells, J., Soledad Fernandez-Alfonso, M., Sengenes, C., Chowen, J. A., Ruiz-Gayo, M. Tags: Research Source Type: research
Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
Neuroendocrine tumours (NETs) may arise throughout the body and are a highly heterogeneous, relatively rare class of neoplasms difficult to study also for the lack of disease models. Despite this, knowledge on their molecular alterations has expanded in the latest years, also building from genetic syndromes causing their onset. Pancreatic NETs (PanNETs) have been among the most studied, and research so far has outlined a series of recurring features, as inactivation of MEN1, VHL, TSC1/2 genes and hyperactivation of the PI3K/mTOR pathway. Next-generation sequencing has added new information by showing the key role of altern...
Source: Journal of Endocrinology - February 6, 2018 Category: Endocrinology Authors: Mafficini, A., Scarpa, A. Tags: Review Source Type: research
The pathogenetic role of {beta}-cell mitochondria in type 2 diabetes
Mitochondrial metabolism is a major determinant of insulin secretion from pancreatic β-cells. Type 2 diabetes evolves when β-cells fail to release appropriate amounts of insulin in response to glucose. This results in hyperglycemia and metabolic dysregulation. Evidence has recently been mounting that mitochondrial dysfunction plays an important role in these processes. Monogenic dysfunction of mitochondria is a rare condition but causes a type 2 diabetes-like syndrome owing to β-cell failure. Here, we describe novel advances in research on mitochondrial dysfunction in the β-cell in type 2 diabetes, with...
Source: Journal of Endocrinology - February 3, 2018 Category: Endocrinology Authors: Fex, M., Nicholas, L. M., Vishnu, N., Medina, A., Sharoyko, V. V., Nicholls, D. G., Spegel, P., Mulder, H. Tags: Review Source Type: research
Attenuation of PERK enhances glucose-stimulated insulin secretion in islets
In conclusion, partial PERK inhibition induced BiP expression in islets, increased glucose-stimulated calcium transit and islet insulin contents and enhanced GSIS, suggesting that low-dose PERK inhibitors could potentially be used to treat insulin deficiency. (Source: Journal of Endocrinology)
Source: Journal of Endocrinology - January 30, 2018 Category: Endocrinology Authors: Kim, M. J., Min, S. H., Shin, S. Y., Kim, M. N., Lee, H., Jang, J. Y., Kim, S.-W., Park, K. S., Jung, H. S. Tags: Research Source Type: research
Melanocortin overexpression limits diet-induced inflammation and atherosclerosis in LDLR-/- mice
In this study, we evaluated the effects of transgenic melanocortin overexpression in a mouse model of atherosclerosis. Low-density lipoprotein receptor-deficient mice overexpressing alpha- and gamma3-MSH (MSH-OE) and their wild-type littermates were fed either a regular chow or Western-style diet for 16 weeks. During this time, their metabolic parameters were monitored. The aortae were collected for functional analysis, and the plaques in the aortic root and arch were characterised by histological and immunohistochemical stainings. The aortic expression of inflammatory mediators was determined by quantitative PCR. We found...
Source: Journal of Endocrinology - January 30, 2018 Category: Endocrinology Authors: Nuutinen, S., Ailanen, L., Savontaus, E., Rinne, P. Tags: Research Source Type: research
Mechanisms of {beta}-cell dedifferentiation in diabetes: recent findings and future research directions
Like all the cells of an organism, pancreatic β-cells originate from embryonic stem cells through a complex cellular process termed differentiation. Differentiation involves the coordinated and tightly controlled activation/repression of specific effectors and gene clusters in a time-dependent fashion thereby giving rise to particular morphological and functional cellular features. Interestingly, cellular differentiation is not a unidirectional process. Indeed, growing evidence suggests that under certain conditions, mature β-cells can lose, to various degrees, their differentiated phenotype and cellular identity...
Source: Journal of Endocrinology - January 18, 2018 Category: Endocrinology Authors: Bensellam, M., Jonas, J.-C., Laybutt, D. R. Tags: Review Source Type: research
Roles of activating functions 1 and 2 of estrogen receptor {alpha} in lymphopoiesis
Apart from the role of sex steroids in reproduction, sex steroids are also important regulators of the immune system. 17β-estradiol (E2) represses T and B cell development, but augments B cell function, possibly explaining the different nature of immune responses in men and women. Both E2 and selective estrogen receptors modulators (SERM) act via estrogen receptors (ER). Activating functions (AF)-1 and 2 of the ER bind to coregulators and thus influence target gene transcription and subsequent cellular response to ER activation. The importance of ERαAF-1 and AF-2 in the immunomodulatory effects of E2/SERM has pr...
Source: Journal of Endocrinology - January 18, 2018 Category: Endocrinology Authors: Andersson, A., Tornqvist, A. E., Moverare-Skrtic, S., Bernardi, A. I., Farman, H. H., Chambon, P., Engdahl, C., Lagerquist, M. K., Windahl, S. H., Carlsten, H., Ohlsson, C., Islander, U. Tags: Research Source Type: research
