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Insulin resistance AND mtor

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https://www.readbyqxmd.com/read/28646031/metabolism-and-acetylation-contribute-to-leucine-mediated-inhibition-of-cardiac-glucose-uptake
#1
Edith Renguet, Audrey Ginion, Roselle Gélinas, Laurent Bultot, Julien Auquier, Isabelle Robillard Frayne, Caroline Daneault, Jean-Louis Vanoverschelde, Christine Des Rosiers, Louis Hue, Sandrine Horman, Christophe Beauloye, Luc Bertrand
High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells suggest that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts...
June 23, 2017: American Journal of Physiology. Heart and Circulatory Physiology
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
#2
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/28590761/proteome-wide-adaptations-of-mouse-skeletal-muscles-during-a-full-month-in-space
#3
Georg Tascher, Thomas Brioche, Pauline Maes, Angèle Chopard, Donal O'Gorman, Guillemette Gauquelin-Koch, Stephane Blanc, Fabrice Bertile
The safety of space flight is challenged by a severe loss of skeletal muscle mass, strength and endurance that may compromise the health and performance of astronauts. The molecular mechanisms underpinning muscle atrophy and decreased performance have been studied mostly after short duration flights, and are still not fully elucidated. By deciphering the muscle proteome changes elicited in mice after a full month aboard the BION-M1 biosatellite, we observed that the antigravity soleus incurred the greatest changes compared to locomotor muscles...
June 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28585197/human-protein-kinases-and-obesity
#4
Atilla Engin
The action of protein kinases and protein phosphatases is essential for multiple physiological responses. Each protein kinase displays its own unique substrate specificity, and a regulatory mechanism that may be modulated by association with other proteins. Protein kinases are classified by the target amino acid in their substrates. Some protein kinases can phosphorylate both serine/threonine, as well as tyrosine residues. This group of kinases has been known as dual specificity kinases. Unlike the dual specificity kinases, a heterogeneous group of protein phosphatases are known as dual-specificity phosphatases...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28574822/endoplasmic-reticulum-stress-induces-autophagy-and-apoptosis-while-inhibiting-proliferation-and-drug-resistance-in-multiple-myeloma-through-the-pi3k-akt-mtor-signaling-pathway
#5
Yun-Feng Fu, Xiao Liu, Meng Gao, Ya-Nan Zhang, Jing Liu
We investigated the effects of endoplasmic reticulum stress (ERS) on autophagy, proliferation, apoptosis, and drug resistance in multiple myeloma (MM). MM patients enrolled in our study (n = 268) were classified into sensitive and resistant groups based on chemotherapy efficacy, and their serum levels of β2-MG, albumin (ALB), lactic dehydrogenase (LDH), Ca2+ and hemoglobin were determined. In addition, human MM U266 and MOLP-2/R cells were divided into blank, tunicamycin (TM), TM + insulin-like growth factor-1 (IGF-1), and TM + rapamycin groups, and measured expression of ERS-related, PI3K/Akt/mTOR pathway-related, and autophagy-related mRNA and proteins...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28573460/brain-glp-1-igf-1-signaling-and-autophagy-mediate-exendin-4-protection-against-apoptosis-in-type-2-diabetic-rats
#6
Emanuel Candeias, Inês Sebastião, Susana Cardoso, Cristina Carvalho, Maria Sancha Santos, Catarina Resende Oliveira, Paula I Moreira, Ana I Duarte
Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin signaling may constitute the crosslink between T2D and AD, its restoration may be potentially therapeutic herein. Accordingly, the insulinotropic anti-T2D drugs from glucagon-like peptide-1 (GLP-1) mimetics, namely, exendin-4 (Ex-4), could be a promising therapy...
June 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28566814/endocrine-responses-and-acute-mtor-pathway-phosphorylation-to-resistance-exercise-with-leucine-and-whey
#7
M T Lane, T J Herda, A C Fry, M A Cooper, M J Andre, P M Gallagher
Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs) provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises...
June 2017: Biology of Sport
https://www.readbyqxmd.com/read/28512156/effects-of-metformin-on-compensatory-pancreatic-%C3%AE-cell-hyperplasia-in-mice-fed-a-high-fat-diet
#8
Kazuki Tajima, Jun Shirakawa, Tomoko Okuyama, Mayu Kyohara, Shunsuke Yamazaki, Yu Togashi, Yasuo Terauchi
Metformin has been widely used for the treatment of type 2 diabetes. However, the effect of metformin on pancreatic β-cells remains controversial. In this study, we investigated the impacts of treatment with metformin on pancreatic β-cells in a mouse model fed a high-fat diet (HFD), which triggers adaptive β-cell replication. An 8-week treatment with metformin improved insulin resistance and suppressed the compensatory β-cell hyperplasia induced by HFD-feeding. In contrast, the increment in β-cell mass arising from 60 weeks of HFD-feeding was similar in mice treated with and those treated without metformin...
May 16, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28452943/pectic-bee-pollen-polysaccharide-from-rosa-rugosa-alleviates-diet-induced-hepatic-steatosis-and-insulin-resistance-via-induction-of-ampk-mtor-mediated-autophagy
#9
Xinzhi Li, Haiquan Gong, Siwen Yang, Lulu Yang, Yuying Fan, Yifa Zhou
Despite it is used as a nutraceutical against diabetes and obesity, the mechanism of action of bee pollen is still unclear. Pectic bee pollen polysaccharide (RBPP-P) was isolated from Rosa rugosa, and its structure was characterized by (13)C-NMR and Fourier transform-infrared spectroscopy (FT-IR). Using high glucose and fatty acids-treated HepG2 cells and high fat diet (HFD)-induced obesity mice, we detected its effect on insulin function and lipid metabolism based on autophagy. RBPP-P contained arabinogalactan, rhamnogalacturonan I, and homogalacturonan domains...
April 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28447735/mice-endometrium-receptivity-in-early-pregnancy-is-impaired-by-maternal-hyperinsulinemia
#10
Runqin Li, Juan Wu, Junlin He, Yingxiong Wang, Xueqing Liu, Xuemei Chen, Chao Tong, Yubin Ding, Yan Su, Wenqi Chen, Chen Zhang, Rufei Gao
Previous studies have investigated the lower embryo implantation rates in women with polycystic ovary syndrome, obesity and type 2 diabetes, and specifically the association between the abnormal oocyte and embryo and hyperinsulinemia. The importance of hyperinsulinemia on maternal endometrium receptivity remains to be elucidated. The present study used a hyperinsulinemic mouse model to determine whether hyperinsulinemia may affect endometrial receptivity. An insulin intervention mouse model was first established...
May 2017: Molecular Medicine Reports
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
#11
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...
June 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28413737/amino-acid-leucine-chromatography-a-study-of-branched-chain-aminoaciduria-in-type-2-diabetes
#12
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
#13
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...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28345313/acute-hyperglycemia-associated-with-anti-cancer-medication
#14
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
#15
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
#16
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
#17
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...
May 1, 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
#18
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
#19
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
#20
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
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