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https://www.readbyqxmd.com/read/28239754/neprilysin-facilitates-adipogenesis-through-potentiation-of-the-phosphatidylinositol-3-kinase-pi3k-signaling-pathway
#1
Juwan Kim, Dasol Han, Sung-Hyun Byun, Mookwang Kwon, Sun-Jung Cho, Young Ho Koh, Keejung Yoon
Neprilysin (NEP) is a zinc metallopeptidase that cleaves a number of small peptides into inactive forms. Despite the recent evidence of a significant correlation between the levels of NEP in plasma and the severity of obesity in humans, a cause-and-effect relationship or a functional role of NEP in obesity has remained uncertain. In this study, we show that NEP has a positive regulatory effect on fat cell formation from precursor cells. NEP increases the accumulation of cytoplasmic triglycerides in 3T3-L1 preadipocytes or the C3H10T1/2 mesenchymal stem cell line in differentiation conditions...
February 27, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28239611/pleotropic-acute-and-chronic-effects-of-leptin-to-reverse-type-1-diabetes
#2
Rachel J Perry
Recent studies have demonstrated that leptin can prolong life chronically in rats with poorly-controlled type 1 diabetes (T1D). Multiple explanations have been proposed to explain leptin's chronic antihyperglycemic effect, including suppression of glucagon release and/or signaling, reductions in hyperphagia and ectopic lipid content, and improvements in insulin sensitivity; it is leptin's ability to reduce plasma glucose relies on all of these effects. In addition, leptin reverses hyperglycemia and diabetic ketoacidosis (DKA) acutely, within 6 hours of leptin infusion, by suppressing hypothalamic-pituitary-adrenal (HPA) axis activity in insulinopenic rats...
January 2017: Postdoc Journal: a Journal of Postdoctoral Research and Postdoctoral Affairs
https://www.readbyqxmd.com/read/28239164/adipocyte-c1qtnf5-expression-is-bmi-dependently-related-to-early-adipose-tissue-dysfunction-and-systemic-ctrp5-serum-levels-in-obese-children
#3
J T Schwartze, K Landgraf, U Spielau, D Rockstroh, D Löffler, J Kratzsch, W Kiess, A Körner
BACKGROUND/OBJECTIVES: The recently identified adipocytokine C1QTNF5 (encodes for CTRP5) has been demonstrated to inhibit pro-metabolic insulin signaling in adipocytes. We hypothesized that adipocyte C1QTNF5 expression in subcutaneous (sc) adipose tissue (AT) would correlate with the degree of obesity, systemic CTRP5 serum levels, and early AT and metabolic dysfunction in children. SUBJECTS/METHODS: Sc AT samples were obtained from 33 healthy Caucasian lean children aged 10...
February 27, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28238722/hormetic-modulation-of-hepatic-insulin-sensitivity-by-advanced-glycation-end-products
#4
Nelly T Fabre, Karina Thieme, Karolline S Silva, Sérgio Catanozi, Ana Mercedes Cavaleiro, Danilo A C Pinto, Maristela M Okamoto, Mychel Raony P T Morais, Bárbara Falquetto, Telma M Zorn, Ubiratan F Machado, Marisa Passarelli, Maria Lúcia Correa-Giannella
Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AlbAGE) or not by advanced glycation for 12 weeks. AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes...
February 23, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28237819/the-complex-roles-of-mechanistic-target-of-rapamycin-in-adipocytes-and-beyond
#5
REVIEW
Peter L Lee, Su Myung Jung, David A Guertin
Having healthy adipose tissue is essential for metabolic fitness. This is clear from the obesity epidemic, which is unveiling a myriad of comorbidities associated with excess adipose tissue including type 2 diabetes, cardiovascular disease, and cancer. Lipodystrophy also causes insulin resistance, emphasizing the importance of having a balanced amount of fat. In cells, the mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2, respectively) link nutrient and hormonal signaling with metabolism, and recent studies are shedding new light on their in vivo roles in adipocytes...
February 22, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28237722/dapper1-attenuates-hepatic-gluconeogenesis-and-lipogenesis-by-activating-pi3k-akt-signaling
#6
Jian-Ren Kuang, Zhi-Hui Zhang, Wei-Ling Leng, Xiao-Tian Lei, Zi-Wen Liang
Studies have shown that hepatic insulin resistance, a disorder of glucose and lipid metabolism, plays a vital role in type 2 diabetes (T2D). To clarify the function of Dapper1 in glucose and lipid metabolism in the liver, we investigated the relationships between Dapper1 and adenosine triphosphate (ATP)- and Ca(2+)-mediated activation of PI3K/Akt. We observed a reduction in hepatic Dapper1 in db/db (mice that are homozygous for a spontaneous diabetes mutation) and HFD-induced diabetic mice with T2D. Hepatic overexpression of Dapper1 improved hyperglycemia, insulin resistance, and fatty liver...
February 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28237651/gip-3-30-nh2-is-a-potent-competitive-antagonist-of-the-gip-receptor-and-effectively-inhibits-gip-mediated-insulin-glucagon-and-somatostation-release
#7
A H Sparre-Ulrich, M N Gabe, L S Gasbjerg, C B Christiansen, B Svendsen, B Hartmann, J J Holst, M M Rosenkilde
Alternative processing of the precursor protein pro-GIP results in endogenously produced GIP(1-30)NH2, that by DPP-4 cleavage in vivo results in the metabolite GIP(3-30)NH2. We showed previously that GIP(3-30)NH2 is a high affinity antagonist of the human GIPR in vitro. Here we determine whether it is suitable for studies of GIP physiology in rats since effects of GIP agonists and antagonists are strictly species-dependent. Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation or assayed in competition binding using human (125)I-GIP(1-42) as radioligand...
February 22, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28236523/acute-but-not-chronic-exposure-to-arsenic-provokes-glucose-intolerance-in-rats-possible-roles-for-oxidative-stress-and-the-adrenergic-pathway
#8
Mohsen Rezaei, Mohammd Javad Khodayar, Enayatollah Seydi, Alboghobeish Soheila, Isa Kazemzadeh Parsi
OBJECTIVES: Health problems due to heavy metals have become a worldwide concern. Along with its carcinogenicity, arsenic exposure results in impairment of glucose metabolism and insulin secretion as well as altered gene expression and signal transduction. However, the exact mechanism behind the behaviour of arsenic on glucose homeostasis and insulin secretion has not yet been fully understood. METHODS: Fasting blood sugar and glucose tolerance tests were evaluated...
February 21, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28236033/co-targeting-the-her-and-igf-insulin-receptor-axis-in-breast-cancer-with-triple-targeting-with-endocrine-therapy-for-hormone-sensitive-disease
#9
Ashok Chakraborty, Christos Hatzis, Michael P DiGiovanna
PURPOSE: Interactions between HER2, estrogen receptor (ER), and insulin-like growth factor I receptor (IGF1R) are implicated in resistance to monotherapies targeting these receptors. We have previously shown in pre-clinical studies synergistic anti-tumor effects for co-targeting each pairwise combination of HER2, IGF1R, and ER. Strikingly, synergy for HER2/IGF1R targeting occurred not only in a HER2+ model, but also in a HER2-normal model. The purpose of the current study was therefore to determine the generalizability of synergistic anti-tumor effects of co-targeting HER2/IGF1R, the anti-tumor activity of triple-targeting HER2/IGF1R/ER in hormone-dependent cell lines, and the effect of using the multi-targeting drugs neratinib (pan-HER) and BMS-754807 (dual IGF1R/insulin receptor)...
February 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28235973/endothelin-signaling-regulates-mineralization-and-posttranscriptionally-regulates-sost-in-tmob-cells-via-mir-126-3p
#10
Michael G Johnson, Kathryn Konicke, Jasmin Kristianto, Anne Gustavson, Rachel Garbo, Xiaohu Wang, Baozhi Yuan, Robert D Blank
Previously, our laboratory identified ECE-1, encoding endothelin-converting enzyme-1 (ECE-1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We hypothesized that endothelin-1 (ET-1) signaling promotes osteogenesis. Exposure of immortalized mouse osteoblast (TMOb) cells to big ET-1 increased mineralization. Following big ET-1 treatment, we measured the secretion of insulin-like-growth factor-1 (IGF1), dickkopf-homolog-1 protein 1 (DKK1), and sclerostin (SOST)...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28230764/cinnamic-acid-and-its-derivatives-mechanisms-for-prevention-and-management-of-diabetes-and-its-complications
#11
REVIEW
Sirichai Adisakwattana
With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications...
February 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28230659/sulfonylurea-blockade-of-k-atp-channels-unmasks-a-distinct-type-of-glucose-induced-ca-2-decrease-in-pancreatic-%C3%AE-cells
#12
Bo Hellman, Heléne Dansk, Eva Grapengiesser
OBJECTIVES: This study aimed to explore how sulfonylurea blockade of KATP channels affects the early Ca signals for glucose generation of insulin release. METHODS: Cytoplasmic Ca was measured with ratiometric microfluorometry in isolated mouse islets loaded with Fura-PE3. RESULTS: After sulfonylurea blockade of the KATP channels (50 μM-1 mM tolbutamide or 1 μM-1 mM gliclazide), increase of glucose from 3 to 20 mM resulted in suppression of elevated Ca during a 3- to 5-minute period...
February 23, 2017: Pancreas
https://www.readbyqxmd.com/read/28229284/prolonged-growth-hormone-insulin-insulin-like-growth-factor-nutrient-response-signaling-pathway-as-a-silent-killer-of-stem-cells-and-a-culprit-in-aging
#13
REVIEW
Mariusz Z Ratajczak, Andrzej Bartke, Zbigniew Darzynkiewicz
The dream of slowing down the aging process has always inspired mankind. Since stem cells are responsible for tissue and organ rejuvenation, it is logical that we should search for encoded mechanisms affecting life span in these cells. However, in adult life the hierarchy within the stem cell compartment is still not very well defined, and evidence has accumulated that adult tissues contain rare stem cells that possess a broad trans-germ layer differentiation potential. These most-primitive stem cells-those endowed with pluripotent or multipotent differentiation ability and that give rise to other cells more restricted in differentiation, known as tissue-committed stem cells (TCSCs) - are of particular interest...
February 22, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28228749/neuroprotective-role-of-the-pi3-kinase-akt-signaling-pathway-in-zebrafish
#14
Shuang Chen, Yunzhang Liu, Xiaozhi Rong, Yun Li, Jianfeng Zhou, Ling Lu
Neuronal survival and growth in the embryo is controlled partly by trophic factors. For most trophic factors (such as Insulin-like growth factor-1), the ability to regulate cell survival has been attributed to the phosphoinositide 3-kinase (PI3K)/Akt kinase cascade. This study presents data illustrating the role of PI3K/Akt in attainment of normal brain size during zebrafish embryogenesis. Blocking PI3K with inhibitor LY294002 caused a significant reduction in brain size (in addition to global growth retardation) during zebrafish embryogenesis...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28228583/food-responsiveness-regulates-episodic-behavioral-states-in-caenorhabditis-elegans
#15
Richard J McCloskey, Anthony D Fouad, Matthew A Churgin, Christopher Fang-Yen
Animals optimize survival and reproduction in part through control of behavioral states, which depend on the organism's internal and external environments. In the nematode C. elegans, a variety of behavioral states have been described, including roaming, dwelling, quiescence, and episodic swimming. These states have been considered in isolation, under varied experimental conditions, making it difficult to establish a unified picture of how they are regulated. Using long-term imaging, we examined C. elegans episodic behavioral states under varied mechanical and nutritional environments...
February 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28228474/changes-in-ambient-temperature-elicit-divergent-control-of-metabolic-and-cardiovascular-actions-by-leptin
#16
Jussara M do Carmo, Alexandre A da Silva, Damian G Romero, John E Hall
Interactions of hypothalamic signaling pathways that control body temperature (BT), blood pressure (BP), and energy balance are poorly understood. We investigated whether the chronic BP and metabolic actions of leptin are differentially modulated by changes in ambient temperature (TA ). Mean arterial pressure (MAP), heart rate (HR), BT, motor activity (MA), and oxygen consumption (Vo2) were measured 24 h/d at normal laboratory TA (23°C), at thermoneutral zone (TNZ, 30°C) for mice or during cold exposure (15°C) in male wild-type mice...
February 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28228267/nrf2-improves-leptin-and-insulin-resistance-provoked-by-hypothalamic-oxidative-stress
#17
Yoko Yagishita, Akira Uruno, Toshiaki Fukutomi, Ritsumi Saito, Daisuke Saigusa, Jingbo Pi, Akiyoshi Fukamizu, Fumihiro Sugiyama, Satoru Takahashi, Masayuki Yamamoto
The relationship between loss of hypothalamic function and onset of diabetes mellitus remains elusive. Therefore, we generated a targeted oxidative-stress murine model utilizing conditional knockout (KO) of selenocysteine-tRNA (Trsp) using rat-insulin-promoter-driven-Cre (RIP-Cre). These Trsp-KO (Trsp(RIP)KO) mice exhibit deletion of Trsp in both hypothalamic cells and pancreatic β cells, leading to increased hypothalamic oxidative stress and severe insulin resistance. Leptin signals are suppressed, and numbers of proopiomelanocortin-positive neurons in the hypothalamus are decreased...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228082/recent-advances-in-protein-tyrosine-phosphatase-1b-targeted-drug-discovery-for-type-ii-diabetes-and-obesity
#18
Neelesh Maheswari, Chandrabose Karthikeyan, Piyush Trivedi, N S Hari Narayana Moorthy
Protein tyrosine phosphatase 1B (PTP1B) is an important therapeutic target for type II diabetes and obesity because of its pivotal role as a negative modulator in both insulin and leptin signalling pathways. Consequently, the discovery of PTP1B inhibitors has been the focus of researchers in both academia and pharmaceutical industry over the last two decades. Though, intense pharmaceutical research in this area has resulted in many potent PTP1B inhibitors, a vast majority of them possessed pTyr mimetic group such as phosphonates, carboxylic acids and sulphamic acids, which led to poor PTP1B selectivity and insufficient in vivo efficacy due to low cell permeability and bioavailability...
February 22, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28226203/characteristic-changes-in-decidual-gene-expression-signature-in-spontaneous-term-parturition
#19
Haidy El-Azzamy, Andrea Balogh, Roberto Romero, Yi Xu, Christopher LaJeunesse, Olesya Plazyo, Zhonghui Xu, Theodore G Price, Zhong Dong, Adi L Tarca, Zoltan Papp, Sonia S Hassan, Tinnakorn Chaiworapongsa, Chong Jai Kim, Nardhy Gomez-Lopez, Nandor Gabor Than
Background: The decidua has been implicated in the "terminal pathway" of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process...
February 22, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28225806/capsaicin-reduces-alzheimer-associated-tau-changes-in-the-hippocampus-of-type-2-diabetes-rats
#20
Weijie Xu, Juanhong Liu, Delin Ma, Gang Yuan, Yan Lu, Yan Yang
Type 2 diabetes (T2D) is a high-risk factor for Alzheimer's disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight...
2017: PloS One
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