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https://www.readbyqxmd.com/read/28330327/role-of-gnb3-net-kcnj11-tcf7l2-and-grl-genes-single-nucleotide-polymorphism-in-the-risk-prediction-of-type-2-diabetes-mellitus
#1
REVIEW
Saliha Rizvi, Syed Tasleem Raza, Qamar Rahman, Farzana Mahdi
Type 2 diabetes (T2DM) is a polygenic metabolic disorder characterized by hyperglycemia occurring as a result of impaired insulin secretion or insulin resistance. Various environmental and genetic factors interact and increase the risk of T2DM and its complications. Among the various genetic factors associated with T2DM, single nucleotide polymorphism in different candidate genes have been studied intensively and the resulting genetic variants have been found to have either positive or negative association with T2DM thereby increasing or decreasing the risk of T2DM, respectively...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#2
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28328831/expression-characteristics-of-proteins-of-igf-1r-p-akt-and-survivin-in-papillary-thyroid-carcinoma-patients-with-type-2-diabetes-mellitus
#3
Yuerong Yan, Fengqiu Hu, Weilu Wu, Ruiting Ma, Hui Huang
Type 2 diabetes mellitus (T2DM) is related to increased risk of papillary thyroid carcinoma (PTC). Insulin-like growth factor-1 receptor (IGF-1R) is increased in patients with T2DM. The increased IGF-1R may be responsible for the development of PTC. In this study, we investigated the expression of phosphorylation of Akt (p-Akt)/survivin pathway activated by IGF-1R in PTC subjects with and without diabetes.Clinicopathological data of 20 PTC patients with T2DM were retrospectively analyzed and compared with those of 21 PTC subjects without diabetes...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28328746/cross-talk-between-insulin-signaling-and-gpcrs
#4
Qin Fu, Qian Shi, Toni M West, Yang K Xiang
Diabetes is a major risk factor for the development of heart failure. One of the hallmarks of diabetes is insulin resistance associated with hyperinsulinemia. The literature shows that insulin and adrenergic signaling is intimately linked to each other; however, whether and how insulin may modulate cardiac adrenergic signaling and cardiac function remains unknown. Notably, recent studies have revealed that insulin receptor and β2 adrenergic receptor (β2AR) forms a membrane complex in animal hearts, bringing together the direct contact between two receptor signaling systems, and forming an integrated and dynamic network...
March 17, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28328012/free-fatty-acid-receptor-1-ffar1-as-an-emerging-therapeutic-target-for-type-2-diabetes-mellitus-recent-progress-and-prevailing-challenges
#5
REVIEW
Zheng Li, Xue Xu, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFAR1/GPR40) amplifies glucose-dependent insulin secretion; therefore, it has attracted widespread attention as a promising antidiabetic target. Current clinical proof of concept also indicates that FFAR1 agonists achieve the initially therapeutic endpoint for the treatment of type 2 diabetes mellitus (T2DM) without the hypoglycemic risk. Thus, many pharmaceutical companies and academic institutes are competing to develop FFAR1 agonists. However, several candidates have been discontinued in clinical trials, often without reporting the underlying reasons...
March 22, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28327432/feedback-from-arctic-charr-feed-flavour-stimulation-and-re-feeding-after-feed-deprivation-stimulate-genes-encoding-both-orexigenic-and-anorexigenic-neuropeptides
#6
Anja Striberny, Even H Jørgensen
Despite vast research attention, the knowledge about central mechanisms of appetite regulation in teleost remains inconclusive. A common strategy in studies on appetite regulating mechanisms is to measure the response to feed restriction or - deprivation, but responses vary between fish species and between experiments, and are also likely dependent on the degree of energy perturbation. The anadromous Arctic charr is an interesting model for studying appetite regulation as its feeding cycle comprises months of winter anorexia, and hyperphagia during summer...
March 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28326758/genetic-determinants-of-low-birth-weight
#7
Theresa Mallia, Alexia Grech, Abigail Hili, Jean Calleja Agius, Nikolai P Pace
Birth weight depends on the elaborate interaction between maternal and foetal genotypes, placental function, maternal nutrition and lifestyle and their effect on epigenetic regulators ofgene activity. The maternal environment in which the foetus develops is a critical factor indetermining birth weight. This review provides an overview of the effect of several geneticvariants leading to intrauterine growth restriction and low birth weight. Irrespective of theexact cause of genetic variations of foetal genes, intrauterine growth restriction is most likelydue to alteration in the growth hormone and insulin like growth factor axis with distinctchanges in the growth factors and their interaction with corresponding receptors...
March 21, 2017: Minerva Ginecologica
https://www.readbyqxmd.com/read/28326339/glucose-dependent-insulinotropic-polypeptide-gip-and-gip-receptor-gipr-genes-an-association-analysis-of-polymorphisms-and-bone-in-young-and-elderly-women
#8
Gaurav Garg, Fiona E McGuigan, Jitender Kumar, Holger Luthman, Valeriya Lyssenko, Kristina Akesson
INTRODUCTION: The gastro-intestinal hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-induced insulin secretion, with bone anabolic effects through GIP receptor (GIPR) in animal models. We explore its potential in humans by analyzing association between polymorphisms (SNPs) in the GIP and GIPR genes with bone phenotypes in young and elderly women. METHODS: Association between GIP (rs2291725) and GIPR (rs10423928) and BMD, bone mineral content (BMC), bone microarchitecture, fracture and body composition was analyzed in the OPRA (75y, n = 1044) and PEAK-25 (25y; n = 1061) cohorts and serum-GIP in OPRA...
June 2016: Bone Reports
https://www.readbyqxmd.com/read/28325871/progression-of-type-1-diabetes-from-the-prediabetic-stage-is-controlled-by-interferon-%C3%AE-signaling
#9
Brett S Marro, Brian C Ware, Jaroslav Zak, Juan Carlos de la Torre, Hugh Rosen, Michael B A Oldstone
Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip-LCMV T1D model. First, treatment with antibody or CYM-5442 limited the migration of autoimmune "antiself" T cells to the external boundaries around the islets and prevented their entry into the islets so they could not be positioned to engage, kill, and thus remove insulin-producing β cells. Second, CYM-5442 induced an exhaustion signature in antiself T cells by up-regulating the negative immune regulator receptor genes Pdcd1, Lag3, Ctla4, Tigit, and Btla, thereby limiting their killing ability...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28325853/deletion-of-macrophage-mineralocorticoid-receptor-protects-hepatic-steatosis-and-insulin-resistance-through-er%C3%AE-hgf-met-pathway
#10
Yu-Yao Zhang, Chao Li, Gao-Feng Yao, Lin-Juan Du, Yuan Liu, Xiao-Jun Zheng, Shuai Yan, Jian-Yong Sun, Yan Liu, Ming-Zhu Liu, Xiaoran Zhang, Gang Wei, Wenxin Tong, Xiaobei Chen, Yong Wu, Shuyang Sun, Suling Liu, Qiurong Ding, Ying Yu, Huiyong Yin, Sheng-Zhong Duan
Although the importance of macrophages in nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) has been recognized, it remains elusive how macrophages impact hepatocytes. Mineralocorticoid receptor (MR) has been implied to play important roles in NAFLD and T2DM. However, cellular and molecular mechanisms are largely unknown. Here we report that myeloid MR knockout (MRKO) improves glucose intolerance, insulin resistance, and hepatic steatosis in obese mice. Estrogen signaling is sufficient and necessary for such improvements...
March 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28325801/insulin-and-glucagon-like-peptide-1-receptor-agonist-combination-therapy-in-type-2-diabetes-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#11
REVIEW
Maria Ida Maiorino, Paolo Chiodini, Giuseppe Bellastella, Annalisa Capuano, Katherine Esposito, Dario Giugliano
OBJECTIVE: The combination of basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1RA) has been proposed as a treatment option to intensify insulin therapy in type 2 diabetes. We performed a meta-analysis of randomized controlled trials (RCTs) comparing this combination strategy to other injectable antidiabetes treatments on metabolic control in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search until November 2016 on many electronic databases to identify RCTs assessing changes in HbA1c, proportion of patients at HbA1c target ≤7% (53 mmol/mol), hypoglycemia, and weight change...
April 2017: Diabetes Care
https://www.readbyqxmd.com/read/28325733/overactivation-of-the-endocannabinoid-system-alters-the-anti-lipolytic-action-of-insulin-in-mouse-adipose-tissue
#12
Tania Muller, Laurent Demizieux, Stéphanie Troy-Fioramonti, Joseph Gresti, Jean-Paul Pais de Barros, Hélène Berger, Bruno Vergès, Pascal Degrace
Evidence has accumulated that obesity-related metabolic dysregulation is associated with overactivation of the endocannabinoid system (ECS), which involves cannabinoid receptor 1 (CB1R), in peripheral tissues, including adipose tissue (AT). The functional consequences of CB1R activation on AT metabolism remain unclear. Since excess fat mobilization is considered an important primary event contributing to the onset of insulin resistance, we combined in vivo and in vitro experiments to investigate whether activation of ECS could alter the lipolytic rate...
March 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324053/hepatic-insulin-resistance-and-altered-gluconeogenic-pathway-in-premature-baboons
#13
Lisa McGill-Vargas, Amalia Gastaldelli, Hanyu Liang, Diana Anzueto Guerra, Teresa Johnson-Pais, Steven Seidner, Donald McCurnin, Giovanna Muscogiuri, Ralph DeFronzo, Nicolas Musi, Cynthia Blanco
Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extra-uterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content and gene expression of key insulin signaling/gluconeogenic molecules...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324037/autotaxin-is-regulated-by-glucose-and-insulin-in-adipocytes
#14
Kenneth D'Souza, Daniel A Kane, Mohamed Touaibia, Erin E Kershaw, Thomas Pulinilkunnil, Petra C Kienesberger
Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid. Despite recent studies implicating adipose-derived ATX in metabolic disorders including obesity and insulin resistance, the nutritional and hormonal regulation of ATX in adipocytes remains unclear. The present study examined the regulation of ATX in adipocytes by glucose and insulin and the role of ATX in adipocyte metabolism. Induction of insulin resistance in adipocytes with high glucose and insulin concentrations increased ATX secretion, whereas co-incubation with the insulin sensitizer, rosiglitazone, prevented this response...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324021/endogenous-calcitonin-gene-related-peptide-regulates-lipid-metabolism-and-energy-homeostasis-in-male-mice
#15
Tian Liu, Akiko Kamiyoshi, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Lei Yang, Megumu Tanaka, Xian Xian, Akira Imai, Liuyu Zhai, Kazutaka Hirabayashi, Kun Dai, Keiya Tanimura, Teng Liu, Nanqi Cui, Kyoko Igarashi, Akihiro Yamauchi, Takayuki Shindo
Calcitonin gene-related peptide (CGRP) is a bioactive peptide produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is largely distributed in the cardiovascular and nervous systems, where it acts as a regulatory factor. CGRP is also expressed in organs and tissues involved in metabolic regulation, including white adipose tissue (WAT), where its function is largely unknown. In this study, we examined the effects of endogenous CGRP on metabolic function. When we administered a high-fat diet to CGRP knockout (CGRP-/-) and wild-type (WT) mice for 10 weeks, we observed that food intake did not differ between the two groups, but body weight and visceral fat weight were significantly lower in CGRP-/- mice...
January 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324020/paracrine-pathways-in-uterine-leiomyoma-stem-cells-involve-insulin-like-growth-factor-2-and-insulin-receptor-a
#16
Molly B Moravek, Ping Yin, John S Coon V, Masanori Ono, Stacy A Druschitz, Saurabh S Malpani, Matthew T Dyson, Alfred W Rademaker, Jared C Robins, Jian-Jun Wei, J Julie Kim, Serdar E Bulun
Context: Uterine leiomyoma (fibroids) are the most common benign tumor in women. Recently, three populations of leiomyoma cells were discovered based on CD34 and CD49b expression, but the molecular differences between these populations remain unknown. Objective: Define differential gene expression and signaling pathways in leiomyoma cell populations. Design: Cells from human leiomyoma were sorted by flow cytometry into three populations: CD34+/CD49b+, CD34+/CD49b-, and CD34-/CD49b-...
January 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324010/separating-the-anti-inflammatory-and-diabetogenic-effects-of-glucocorticoids-through-lxr%C3%AE-antagonism
#17
Rucha Patel, Lilia Magomedova, Ricky Tsai, Stéphane Angers, Arturo Orellana, Carolyn L Cummins
Synthetic glucocorticoids (GCs) including dexamethasone (DEX) are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The glucocorticoid receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes involved in gluconeogenesis and inflammation. We have previously shown that Lxrβ-/- mice are resistant to the diabetogenic effects of DEX, but still sensitive to its immunosuppressive actions...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323991/whole-body-vibration-mimics-the-metabolic-effects-of-exercise-in-male-leptin-receptor-deficient-mice
#18
Meghan E McGee-Lawrence, Karl H Wenger, Sudipta Misra, Catherine L Davis, Norman K Pollock, Mohammed Elsalanty, Kehong Ding, Carlos M Isales, Mark W Hamrick, Joanna R Erion, Marlena Wosiski-Kuhn, Phonepasong Arounleut, Mark P Mattson, Roy G Cutler, Jack C Yu, Alexis M Stranahan
Whole-body vibration has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether whole-body vibration recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wildtype (Wt) and leptin receptor deficient (db/db) mice to daily treadmill exercise or whole-body vibration for three months. Body weights were analyzed and compared with Wt and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following treadmill exercise or whole-body vibration...
March 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323977/short-term-vs-long-term-effects-of-adipocyte-toll-like-receptor-4-activation-on-insulin-resistance-in-male-mice
#19
Caroline Tao, William L Holland, Qiong A Wang, Mengle Shao, Lin Jia, Kai Sun, Xiaoli Lin, Yi-Chun Kuo, Joshua A Johnson, Ruth Gordillo, Joel K Elmquist, Philipp E Scherer
Chronic exposure to diets high in saturated fat (HFD) increases the prevalence of obesity and contributes to the development of low-grade inflammation and insulin resistance. A possible mediator accounting for obesity-associated inflammation and insulin resistance is Toll-like receptor 4 (TLR4). We investigated the role of adipocyte TLR4 in lipid and glucose homeostasis through an inducible, adipocyte-specific deletion of TLR4, the "TADIPO mouse". Consistent with a critical role for inflammation as a positive force for healthy adipose tissue expansion, chronic HFD exposure resulted in exacerbated whole body and muscle insulin resistance in the absence of TLR4 in the adipocyte...
February 24, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323968/impaired-glycine-mia-in-type-2-diabetes-and-potential-mechanisms-contributing-to-glucose-homeostasis
#20
Richard Yan-Do, Patrick E MacDonald
The onset and/or progression of type 2 diabetes (T2D) can be prevented if intervention is early enough. As such, much effort has been placed on the search for indicators predictive of pre-diabetes and disease onset or progression. An increasing body of evidence suggests that changes in plasma glycine may be one such biomarker. Circulating glycine levels are consistently low in patients with T2D. Levels of this non-essential amino acid correlate negatively with obesity and insulin resistance. Plasma glycine correlates positively with glucose disposal, and rises with interventions such as exercise and bariatric surgery that improve glucose homeostasis...
March 15, 2017: Endocrinology
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