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Insulin resistance AND mtor

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https://www.readbyqxmd.com/read/28440057/overcoming-linsitinib-intrinsic-resistance-through-inhibition-of-nuclear-factor-%C3%AE%C2%BAb-signaling-in-esophageal-squamous-cell-carcinoma
#1
Junzhou Wu, Kaiyan Chen, Fanrong Zhang, Jiaoyue Jin, Nan Zhang, Dan Li, Lisha Ying, Wei Chen, Herbert Yu, Weimin Mao, Dan Su
The aim of this study is to evaluate the efficacy of insulin-like growth factor 1 receptor (IGF-1R) inhibitor Linsitinib, in esophageal squamous cell carcinoma (ESCC), and to characterize special biomarker to screen Linsitinib-sensitive patients as well as explore the molecular-resistant mechanism to Linsitinib in ESCC. Our study evaluated the sensitivity of insulin-like growth factor 1 receptor (IGF-1R) inhibitor, Linsitinib in ESCC cells with MTT assay. After Linsitinib treatment, the expressions of downstream signaling molecules and apoptosis pathways were measured by western blot...
April 24, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28413737/amino-acid-leucine-chromatography-a-study-of-branched-chain-aminoaciduria-in-type-2-diabetes
#2
Bhagavan Reddy Kolanu, Venugopal Boddula, Sabitha Vadakedath, Venkataramana Kandi
INTRODUCTION: Diabetes is a disease characterized by insulin deficiency resulting in glucose intolerance and in abnormalities of other metabolic fuels including protein. Recently, a number of studies have revealed that branched-chain amino acids (BCAAs) (leucine, isoleucine, and valine) play an important role in the regulation of protein synthesis by activating mammalian target of rapamycin (mTOR) in pancreatic β cells. BCAAs have positive effects on the regulation of glucose homeostasis...
March 12, 2017: Curēus
https://www.readbyqxmd.com/read/28402933/pdk1-inhibitor-gsk2334470-exerts-antitumor-activity-in-multiple-myeloma-and-forms-a-novel-multitargeted-combination-with-dual-mtorc1-c2-inhibitor-pp242
#3
Chunmei Yang, Xianbo Huang, Hui Liu, Feng Xiao, Jueying Wei, Liangshun You, Wenbin Qian
A deeper understanding of the complex pathogenesis of multiple myeloma (MM) continues to lead to novel therapeutic approaches. Prior studies suggest that 3-phosphoinositide-dependent kinase 1 (PDK1) is expressed and active, acting as a crucial regulator of molecules that are essential for myelomagenesis. In the present study, we show that GSK2334470 (GSK-470), a novel and highly specific inhibitor of PDK1, induces potent cytotoxicity in MM cell lines including Dexamethasone-resistant cell line, but not in human normal cells...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28345313/acute-hyperglycemia-associated-with-anti-cancer-medication
#4
REVIEW
Yul Hwangbo, Eun Kyung Lee
Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output...
March 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28317262/hydroxytyrosol-restores-proper-insulin-signaling-in-an-astrocytic-model-of-alzheimer-s-disease
#5
M Carmen Crespo, Joao Tomé-Carneiro, Cristina Pintado, Alberto Dávalos, Francesco Visioli, Emma Burgos-Ramos
Recent epidemiological evidence demonstrated that diabetes is a risk factor for AD onset and development. Indeed, meta-analyses of longitudinal epidemiologic studies show that diabetes increases AD risk by 50-100%, being insulin resistance (IR) the main binding link between diabetes and AD. Astrocytes are the foremost cerebral macroglial cells and are responsible for converting glucose into lactate and transfer it to neurons that use it as fuel, but Aβ(1-42) impairs insulin signaling and glycogen storage. Recent prospective studies showed that the Mediterranean diet is associated with lower incidence of AD...
March 20, 2017: BioFactors
https://www.readbyqxmd.com/read/28315335/microrna-99a-inhibits-insulin-induced-proliferation-migration-dedifferentiation-and-rapamycin-resistance-of-vascular-smooth-muscle-cells-by-inhibiting-insulin-like-growth-factor-1-receptor-and-mammalian-target-of-rapamycin
#6
Zi-Wei Zhang, Rui-Wei Guo, Jin-Lin Lv, Xian-Mei Wang, Jin-Shan Ye, Ni-Hong Lu, Xing Liang, Li-Xia Yang
Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells...
April 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28300563/sestrin-2-induces-autophagy-and-attenuates-insulin-resistance-by-regulating-ampk-signaling-in-c2c12-myotubes
#7
Huige Li, Sujuan Liu, Hairui Yuan, Yanmei Niu, Li Fu
Impaired insulin-stimulated glucose uptake in skeletal muscle serves a critical role in the development of insulin resistance (IR), whereas the precise mechanism of the process remains unknown. Recently, the evolutionarily conserved, stress-inducible protein Sestrin2 (Sesn2) has been proposed to play a protective role against obesity-induced IR and diabetes. Activation of Sesn2 may activate AMP-activated protein kinase (AMPK) accompanied by suppression of mammalian target of rapamycin (mTOR), which may ultimately lead to autophagy induction...
March 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28296942/co-ingestion-of-carbohydrate-and-whey-protein-increases-fasted-rates-of-muscle-protein-synthesis-immediately-after-resistance-exercise-in-rats
#8
Wanyi Wang, Zhenping Ding, Geoffrey J Solares, Soon-Mi Choi, Bo Wang, Aram Yoon, Roger P Farrar, John L Ivy
The objective of the study was to investigate whether co-ingestion of carbohydrate and protein as compared with protein alone augments muscle protein synthesis (MPS) during early exercise recovery. Two months old rats performed 10 repetitions of ladder climbing with 75% of body weight attached to their tails. Placebo (PLA), whey protein (WP), or whey protein plus carbohydrate (CP) was then given to rats by gavage. An additional group of sedentary rats (SED) was used as controls. Blood samples were collected immediately and at either 1 or 2 h after exercise...
2017: PloS One
https://www.readbyqxmd.com/read/28275367/ppar-%C3%AE-agonists-as-antineoplastic-agents-in-cancers-with-dysregulated-igf-axis
#9
REVIEW
Veronica Vella, Maria Luisa Nicolosi, Stefania Giuliano, Maria Bellomo, Antonino Belfiore, Roberta Malaguarnera
It is now widely accepted that insulin resistance and compensatory hyperinsulinemia are associated to increased cancer incidence and mortality. Moreover, cancer development and progression as well as cancer resistance to traditional anticancer therapies are often linked to a deregulation/overactivation of the insulin-like growth factor (IGF) axis, which involves the autocrine/paracrine production of IGFs (IGF-I and IGF-II) and overexpression of their cognate receptors [IGF-I receptor, IGF-insulin receptor (IR), and IR]...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28274349/sex-hormones-and-acne
#10
Qiang Ju, Tao Tao, Tingting Hu, Ayşe Serap Karadağ, Safaa Al-Khuzaei, WenChieh Chen
The skin is an endocrine organ with the expression of metabolizing enzymes and hormone receptors for diverse hormones. The sebaceous gland is the main site of hormone biosynthesis, especially for androgens, and acne is the classical androgen-mediated dermatosis. In sebocytes, conversion of 17-hydroxyprogesterone directly to dihydrotestosterone bypassing testosterone has been demonstrated, while type II 17β-hydroxysteroid dehydrogenase can inactivate the action of testosterone and dihydrotestosterone. The androgen receptor-dependent genomic effect of dihydrotestosterone on sebocytes is confirmed...
March 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28272775/cryptotanshinone-inhibition-of-mammalian-target-of-rapamycin-pathway-is-dependent-on-oestrogen-receptor-alpha-in-breast-cancer
#11
Yanhong Pan, Junfeng Shi, Wenting Ni, Yuping Liu, Siliang Wang, Xu Wang, Zhonghong Wei, Aiyun Wang, Wenxing Chen, Yin Lu
Cryptotanshinone (CPT) has been demonstrated to inhibit proliferation and mammalian target of rapamycin (mTOR) pathway in MCF-7 breast cancer cells. However, the same results are unable to be repeated in MDA-MB-231 cells. Given the main difference of oestrogen receptor α (ERα) between two types of breast cancer cells, It is possibly suggested that CPT inhibits mTOR pathway dependent on ERα in breast cancer. CPT could significantly inhibit cell proliferation of ERα-positive cancer cells, whereas ERα-negative cancer cells are insensitive to CPT...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28263222/mtor-and-cardiovascular-diseases-diabetes-mellitus
#12
Bruno Vergès
The mammalian targets of rapamycin (mTOR) inhibitors are potent immunosuppressors used for prevention of acute rejection following transplantation and have been more recently used as anticancer drugs. mTOR inhibitors have a significant impact on glucose metabolism and induce frequently diabetes. mTOR inhibitors, when used as immunosuppressive agents (sirolimus, everolimus), can induce diabetes with an incidence which is low when used without calcineurin inhibitors (CNI) but high when used in combination with CNI (from 11...
March 4, 2017: Transplantation
https://www.readbyqxmd.com/read/28257663/molecular-pathways-related-to-the-longevity-promotion-and-cognitive-improvement-of-cistanche-tubulosa-in-drosophila
#13
Wei-Yong Lin, Chun Yao, Jack Cheng, Shung-Te Kao, Fuu-Jen Tsai, Hsin-Ping Liu
BACKGROUND: The aging process, including physical dysfunction and age-related memory impairment (AMI), are considered to be correlated with cumulative oxidative damages and insulin/IGF-1 signaling pathway. PURPOSE: The present study was to elucidate the in vivo effects on delaying aging and ameliorating AMI and underlying molecular mechanisms of Cistanche tubulosa (CT), a herb used in traditional Chinese medicine to improve sexual function and treat kidney dysfunction...
March 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28252104/altered-gene-expression-and-repressed-markers-of-autophagy-in-skeletal-muscle-of-insulin-resistant-patients-with-type-2-diabetes
#14
Andreas Buch Møller, Ulla Kampmann, Jakob Hedegaard, Kasper Thorsen, Iver Nordentoft, Mikkel Holm Vendelbo, Niels Møller, Niels Jessen
This case-control study was designed to investigate the gene expression profile in skeletal muscle from severely insulin resistant patients with long-standing type 2 diabetes (T2D), and to determine associated signaling pathways. Gene expression profiles were examined by whole transcriptome, strand-specific RNA-sequencing and associated signaling was determined by western blot. We identified 117 differentially expressed gene transcripts. Ingenuity Pathway Analysis related these differences to abnormal muscle morphology and mitochondrial dysfunction...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28237819/the-complex-roles-of-mechanistic-target-of-rapamycin-in-adipocytes-and-beyond
#15
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/28196954/metformin-and-thyroid-disease
#16
REVIEW
Xianghui Meng, Shuhang Xu, Guofang Chen, Michael Derwahl, Chao Liu
An intriguing area of research in thyroidology is the recently discovered association of insulin resistance with thyroid functional and morphological abnormalities. Individuals with hyperinsulinemia have larger thyroid gland and a higher prevalence of thyroid nodules and cancer. Accordingly, patients treated with metformin have a smaller thyroid volume and a lower risk of incident goiter, thyroid nodule and cancer. Multiple studies in vitro and in vivo have demonstrated that metformin can inhibit the growth of thyroid cells and different types of thyroid cancer cells by affecting the insulin/IGF1 and mTOR pathways...
April 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28185837/insulin-promotes-her2-signaling-activation-during-barrett-s-esophagus-carcinogenesis
#17
Diletta Arcidiacono, Alessandro Antonello, Matteo Fassan, Daniele Nucci, Tiziana Morbin, Marco Agostini, Donato Nitti, Massimo Rugge, Alfredo Alberti, Giorgio Battaglia, Stefano Realdon
BACKGROUND: Insulin-resistance and hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion Barrett's Esophagus (BE). HER2 activation has also a pivotal role in EAC carcinogenesis but no data correlate these two phenomena in this disease context. AIMS: To investigate the role of hyperinsulinemia in BE-dysplasia-adenocarcinoma sequence and the possible relationship between insulin-mediated and HER2 signaling in EAC development...
January 22, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28179884/cellular-signaling-pathways-in-insulin-resistance-systems-biology-analyses-of-microarray-dataset-reveals-new-drug-target-gene-signatures-of-type-2-diabetes-mellitus
#18
Syed Aun Muhammad, Waseem Raza, Thanh Nguyen, Baogang Bai, Xiaogang Wu, Jake Chen
Purpose: Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder affecting large set of population of the world. To widen the scope of understanding of genetic causes of this disease, we performed interactive and toxicogenomic based systems biology study to find potential T2DM related genes after cDNA differential analysis. Methods: From the list of 50-differential expressed genes (p < 0.05), we found 9-T2DM related genes using extensive data mapping. In our constructed gene-network, T2DM-related differentially expressed seeder genes (9-genes) are found to interact with functionally related gene signatures (31-genes)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28168653/effects-of-a-hyperandrogenaemic-state-on-the-proliferation-and-decidualization-potential-in-human-endometrial-stromal-cells
#19
Alexander Freis, Tobias Renke, Ulrike Kämmerer, Julia Jauckus, Thomas Strowitzki, Ariane Germeyer
OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, involving hyperandrogenaemia and insulin resistance. Treatment options include dexamethasone, as well as the off-label use of metformin. To evaluate the impact of those drugs on cyclic changes in endometrial development, we tested possible effects of metformin and dexamethasone on endometrial stromal cells decidualisation, proliferation, and gene regulation in a hyperandrogenaemic microenvironment in vitro...
February 6, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28153729/4-pba-reverses-autophagic-dysfunction-and-improves-insulin-sensitivity-in-adipose-tissue-of-obese-mice-via-akt-mtor-signaling
#20
Qinyue Guo, Lin Xu, Huixia Li, Hongzhi Sun, Shufang Wu, Bo Zhou
BACKGROUND: 4-phenyl butyric acid (4-PBA) has been considered as a key regulator of insulin resistance in obesity. However the mechanism of 4-PBA involved in insulin resistance remains elusive. METHODS: We evaluated the effect of 4-PBA on abnormal autophagy and endoplasmic reticulum (ER) stress in obese mice. 4-PBA was administered in obese mice and adipocyte models, and metabolic parameters, autophagy markers, ER stress indicators, Akt/mTOR signaling and insulin signaling molecular were assessed...
March 11, 2017: Biochemical and Biophysical Research Communications
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