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https://www.readbyqxmd.com/read/28637102/-the-progression-of-liver-fibrosis-in-non-alcoholic-fatty-liver-disease
#1
REVIEW
Moon Young Kim
Understanding the pathogenesis of non-alcoholic steatohepatitis (NASH) and its fibrosis progression is still evolving. Nonetheless, current evidence suggests that mechanisms involved are very complex parallel processes with multiple metabolic factors. Lipotoxicity related with excess saturated free fatty acids, obesity, and insulin resistance acts as the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence are also contribute to the activation of inflammasome via various intra- and inter-cellular signaling mechanisms that lead to fibrosis...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28636047/decoding-the-regulatory-mechanism-of-glucose-and-insulin-induced-phosphatidylinositol-3-4-5-trisphosphate-dynamics-in-%C3%AE-cells
#2
Tagari Samanta, Peeyush Sharma, Dwijendra Kukri, Sandip Kar
In MIN6 pancreatic β-cells, glucose and insulin act in a synergistic manner to regulate the dynamics of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3). However, the precise regulatory mechanism behind such an experimentally observed synergy is poorly understood. In this article, we propose a phenomenological mathematical model for studying the glucose and insulin driven PIP3 activation dynamics under various stimulatory conditions to unfold the mechanism responsible for the observed synergy. The modeling study reveals that the experimentally observed oscillation in PIP3 dynamics with disparate time scales for different external glucose doses is mainly orchestrated by the complex dynamic regulation of cytosolic Ca(2+) in β-cells...
June 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28635658/asperentin-b-a-new-inhibitor-of-the-protein-tyrosine-phosphatase-1b
#3
Jutta Wiese, Hülya Aldemir, Rolf Schmaljohann, Tobias A M Gulder, Johannes F Imhoff
In the frame of studies on secondary metabolites produced by fungi from deep-sea environments we have investigated inhibitors of enzymes playing key roles in signaling cascades of biochemical pathways relevant for the treatment of diseases. Here we report on a new inhibitor of the human protein tyrosine phosphatase 1B (PTP1B), a target in the signaling pathway of insulin. A new asperentin analog is produced by an Aspergillussydowii strain isolated from the sediment of the deep Mediterranean Sea. Asperentin B (1) contains an additional phenolic hydroxy function at C-6 and exhibits an IC50 value against PTP1B of 2 μM in vitro, which is six times stronger than the positive control, suramin...
June 21, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28634451/berberine-ameliorates-diabetes-associated-cognitive-decline-through-modulation-of-aberrant-inflammation-response-and-insulin-signaling-pathway-in-dm-rats
#4
Qingjie Chen, Ran Mo, Ninghua Wu, Xin Zou, Cai Shi, Jing Gong, Jingbin Li, Ke Fang, Dingkun Wang, Deshen Yang, Kaifu Wang, Juan Chen
Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer's disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28633870/omega-3-free-fatty-acids-attenuate-insulin-promoted-breast-cancer-cell-proliferation
#5
Yang Guo, Sheng-Long Zhu, Yi-Kuan Wu, Zhao He, Yong-Quan Chen
High insulin levels in obese people are considered as a risk factor to induce breast carcinogenesis. And consumption of fish oils which mainly contain omega-3 fatty acids is associated with a reduced risk of breast cancer. However, whether omega-3 free fatty acids (FFAs) modulate insulin signaling pathway to prevent breast cancer is poorly understood. The current study tested the hypothesis that omega-3 FFAs attenuate insulin-induced breast cancer cell proliferation and regulate insulin signaling pathway. We show here that omega-3 FFAs attenuate MCF-7 cell proliferation and Akt and Erk1/2 phosphorylation levels stimulated by insulin...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28633482/markers-of-adipogenesis-but-not-inflammation-in-adipose-tissue-are-independently-related-to-insulin-sensitivity
#6
Natalia Matulewicz, Magdalena Stefanowicz, Agnieszka Nikolajuk, Monika Karczewska-Kupczewska
Context: In obesity, adipose tissue (AT) undergoes dynamic remodeling, including an alternations in adipogenesis, AT-resident cell content, angiogenesis and turnover of extracellular matrix (ECM) components. Studies on AT in humans have been carried out mostly on people with severe metabolic abnormalities, like type 2 diabetes or morbid obesity. Objective: The purpose of the present study was to investigate subcutaneous AT gene expression of markers of adipogenesis, ECM remodeling and inflammation in young, healthy, overweight or obese subjects...
June 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28632756/identification-of-atf-7-and-the-insulin-signaling-pathway-in-the-regulation-of-metallothionein-in-c-elegans-suggests-roles-in-aging-and-reactive-oxygen-species
#7
Julie A Hall, Matthew K McElwee, Jonathan H Freedman
It has been proposed that aging results from the lifelong accumulation of intracellular damage via reactions with reactive oxygen species (ROS). Metallothioneins are conserved cysteine-rich proteins that function as efficient ROS scavengers and may affect longevity. To better understand mechanisms controlling metallothionein expression, the regulatory factors and pathways that controlled cadmium-inducible transcription of the C. elegans metallothionein gene, mtl-1, were identified. The transcription factor ATF-7 was identified in both ethylmethanesulfonate mutagenesis and candidate gene screens...
2017: PloS One
https://www.readbyqxmd.com/read/28632505/obesity-and-prostate-cancer
#8
Marco Bandini, Giorgio Gandaglia, Alberto Briganti
PURPOSE OF REVIEW: To investigate the association between obesity and prostate cancer (PCa). RECENT FINDINGS: Obesity has been proposed to be involved in the pathogenesis of PCa through different biological mechanisms that include deregulation of the insulin axis, sex hormone secretion, adipokines signaling, and oxidative stress. Hypertrophic peritumoral adipocytes may also facilitate the local spread of PCa through the chemo-attraction of tumor cells. Clinical studies demonstrate that obesity might have clinical implications also in disease detection and management...
June 16, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28632493/interplay-between-papp-a-inflammation-and-adiposity-in-patients-with-angiographically-proven-acute-coronary-syndrome-acs
#9
Khageshwar Mahato, Moushumi Lodh, Ashok Parida, Ashok Kr Ahirwar, Rashmi Rasi Datta, Binita Goswami
Introduction Studies conducted in the recent past have demonstrated the role of inflammation, obesity and dysfunctional insulin signaling as contributing factors in the pathogenesis of acute coronary syndrome (ACS). However, pharmacological interventions targeting a single pathway have not proven useful in the long run. This indicates that a synergism occurs between the various risk factors and hence calls for a combinatorial approach. This study was planned to study the interplay, if any, between pregnancy associated plasma protein-A (PAPP-A), inflammation and adiposity in patients with ACS...
June 21, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28631352/overexpressing-stamp2-attenuates-adipose-tissue-angiogenesis-and-insulin-resistance-in-diabetic-apoe-ldlr-mouse-via-a-ppar%C3%AE-cd36-pathway
#10
Feng Wang, Lu Han, Ran-Ran Qin, Yao-Yuan Zhang, Di Wang, Zhi-Hao Wang, Meng-Xiong Tang, Yun Zhang, Ming Zhong, Wei Zhang
The aim of this study was to investigate whether overexpression of STAMP2 improves insulin resistance by regulating angiogenesis in adipose tissues. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. Samples were obtained from epididymal, subcutaneous and brown adipose tissues. Histological and morphological analysis demonstrated that STAMP2 gene overexpression reduced adipocyte size, angiogenesis in epididymal and brown adipose tissues. On aortic ring assay, microvessels sprouting from aortas were significantly inhibited after STAMP2 gene overexpression...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28631330/foxo-transcription-factors-at-the-interface-of-metabolism-and-cancer
#11
REVIEW
Wolfgang Link, Pablo J Fernandez-Marcos
Diabetes refers to a group of metabolic diseases characterized by impaired insulin signalling and high blood glucose. A growing body of epidemiological evidence links diabetes to several types of cancer but the underlying molecular mechanisms are poorly understood. The signalling cascade connecting insulin and FOXO proteins provides a compelling example for a conserved pathway at the interface between insulin signalling and cancer. FOXOs are transcription factors that orchestrate programs of gene expression known to control a variety of processes in response to cellular stress...
June 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28630896/the-gh-receptor-exon-3-deletion-is-a-marker-of-male-specific-exceptional-longevity-associated-with-increased-gh-sensitivity-and-taller-stature
#12
Danny Ben-Avraham, Diddahally R Govindaraju, Temuri Budagov, Delphine Fradin, Peter Durda, Bing Liu, Sandy Ott, Danielle Gutman, Lital Sharvit, Robert Kaplan, Pierre Bougnères, Alex Reiner, Alan R Shuldiner, Pinchas Cohen, Nir Barzilai, Gil Atzmon
Although both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) signaling were shown to regulate life span in lower organisms, the role of GH signaling in human longevity remains unclear. Because a GH receptor exon 3 deletion (d3-GHR) appears to modulate GH sensitivity in humans, we hypothesized that this polymorphism could play a role in human longevity. We report a linear increased prevalence of d3-GHR homozygosity with age in four independent cohorts of long-lived individuals: 841 participants [567 of the Longevity Genes Project (LGP) (8% increase; P = 0...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28630460/oxidative-and-endoplasmic-reticulum-stress-is-impaired-in-leukocytes-from-metabolically-unhealthy-vs-healthy-obese-individuals
#13
C Bañuls, S Rovira-Llopis, S Lopez-Domenech, N Diaz-Morales, A Blas-Garcia, S Veses, C Morillas, V M Victor, M Rocha, A Hernandez-Mijares
BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO), and 31 had type 2 diabetes (MADO)...
June 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28630133/dual-regulation-of-gluconeogenesis-by-insulin-and-glucose-in-the-proximal-tubules-of-the-kidney
#14
Motohiro Sasaki, Takayoshi Sasako, Naoto Kubota, Yoshitaka Sakurai, Iseki Takamoto, Tetsuya Kubota, Reiko Inagi, George Seki, Moritaka Goto, Kohjiro Ueki, Masaomi Nangaku, Takahito Jomori, Takashi Kadowaki
Growing attention has been focused on the roles of the proximal tubules (PTs) of the kidney in glucose metabolism, including the mechanism of regulation of gluconeogenesis. Here, we found that PT-specific IRS1/2 double-knockout mice, established by using the newly generated sodium-glucose cotransporter-2 (SGLT2)-Cre transgenic mice, exhibited impaired insulin signaling and upregulated gluconeogenic gene expression and renal gluconeogenesis, resulting in systemic insulin resistance. On the other hand, in streptozotocin-treated mice, although insulin action was impaired in the PTs, the gluconeogenic gene expression was unexpectedly downregulated in the renal cortex, which was restored by administration of an SGLT1/2 inhibitor...
June 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28629513/erythropoietin-and-hypothalamic-pituitary-axis
#15
Soumyadeep Dey, Constance T Noguchi
Erythropoietin (EPO), known primarily for its erythropoietic activity, is commonly used clinically to treat anemia of chronic kidney disease. However, the expression of EPO receptor (EpoR) beyond erythroid tissue provides for potential extrahematopoietic effects of EPO, including EPO regulation of metabolic homeostasis (Zhang et al., 2014). Small clinical studies have shown that EPO treatment in patients with end-stage renal disease improved glycemic control and insulin sensitivity. Studies in animal models have shown that EPO regulation of metabolism is mainly attributed to its response in fat, and the hypothalamus-pituitary axis (Dey et al...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28627773/oleanolic-acid-derivative-dks26-exerts-antidiabetic-and-hepatoprotective-effects-in-diabetic-mice-and-promotes-glp-1-secretion-and-expression-in-intestinal-cells
#16
Fei-Fei Chen, Jian-Ta Wang, Li-Xia Zhang, Shu-Fang Xing, Yun-Xia Wang, Kai Wang, Shu-Li Deng, Ji-Quan Zhang, Lei Tang, Hao-Shu Wu
BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) is an important target for diabetes therapy based on its key role in maintaining glucose and lipid homeostasis. This study was designed to investigate antidiabetic and hepatoprotective effects of novel oleanolic acid derivative DKS26 in diabetic mice and elucidate its underlying GLP-1 related antidiabetic mechanisms in vitro and in vivo. EXPERIMENTAL APPROACH: The therapeutic effects of DKS26 were inspected in streptozotocin (STZ)-induced and db/db diabetic mouse models including levels of plasma glucose, glycosylated serum protein (GSP), lipid profiles, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), oral glucose tolerance (OGT), pancreatic islets and hepatic histopathological morphology, liver lipid levels and expression of pro-inflammation cytokines...
June 19, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28627605/mesenchymal-stem-cells-promote-endothelial-progenitor-cell-proliferation-by-secreting-insulin%C3%A2-like-growth-factor%C3%A2-1
#17
Jixue Hou, Xinyu Peng, Jing Wang, Hongwei Zhang, Jie Xia, Quanhu Ge, Xiaoyi Wang, Xueling Chen, Xiangwei Wu
Bone marrow mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) interact with each other. EPCs are able to promote the self‑renewal of MSCs as niche cells in murine bone marrow, and MSCs are able to promote EPC proliferation in vitro in a co‑culture system. It has previously been reported that MSCs can secrete insulin‑like growth factor‑1 (IGF‑1), which serves critical functions in EPC proliferation. However, the mechanism underlying the IGF‑1‑mediated proliferation of EPCs remains unclear...
June 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627510/glycogen-controls-caenorhabditis-elegans-lifespan-and-resistance-to-oxidative-stress
#18
Ivan Gusarov, Bibhusita Pani, Laurent Gautier, Olga Smolentseva, Svetlana Eremina, Ilya Shamovsky, Olga Katkova-Zhukotskaya, Alexander Mironov, Evgeny Nudler
A high-sugar diet has been associated with reduced lifespan in organisms ranging from worms to mammals. However, the mechanisms underlying the harmful effects of glucose are poorly understood. Here we establish a causative relationship between endogenous glucose storage in the form of glycogen, resistance to oxidative stress and organismal aging in Caenorhabditis elegans. We find that glycogen accumulated on high dietary glucose limits C. elegans longevity. Glucose released from glycogen and used for NADPH/glutathione reduction renders nematodes and human hepatocytes more resistant against oxidative stress...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28627250/exploring-the-frequency-domain-of-continuous-glucose-monitoring-signals-to-improve-characterization-of-glucose-variability-and-of-diabetic-profiles
#19
Giuseppe Fico, Liss Hernández, Jorge Cancela, Miguel María Isabel, Andrea Facchinetti, Chiara Fabris, Rafael Gabriel, Claudio Cobelli, María Teresa Arredondo Waldmeyer
BACKGROUND: Continuous glucose monitoring (CGM) devices measure interstitial glucose concentrations (normally every 5 minutes), allowing observation of glucose variability (GV) patterns during the whole day. This information could be used to improve prescription of treatments and of insulin dosages for people suffering diabetes. Previous efforts have been focused on proposing indices of GV either in time or glucose domains, while the frequency domain has been explored only partially. The aim of this work is to explore the CGM signal in the frequency domain to understand if new indexes or features could be identified and contribute to a better characterization of glucose variability...
January 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28626222/the-role-of-epigenetics-in-renal-ageing
#20
REVIEW
Paul G Shiels, Dagmara McGuinness, Maria Eriksson, Jeroen P Kooman, Peter Stenvinkel
An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin...
June 19, 2017: Nature Reviews. Nephrology
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