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Xin Li, Shi-Jie Jin, Jie Su, Xiao-Xue Li, Ming Xu
Insulin resistance in endothelial cells contributes to the development of cardiovascular disease in patients with type 2 diabetes. Acid sphingomyelinase (ASM) is a soluble glycoprotein which plays a vital role in the development and progression of various diseases such as cardiovascular and metabolic diseases. However, it remains unknown if ASM regulates insulin resistance in vascular endothelial cells in type 2 diabetes. ASM down-regulation with gene silencing and selective inhibitor amitriptyline was used in the rat aortic endothelial cells (RAECs) treated with palmitic acid (PA), a common saturated free fatty acid, which is thought to be the major cause of insulin resistance...
June 19, 2018: Basic & Clinical Pharmacology & Toxicology
Yuliya Skorobogatko, Morgan Dragan, Claudia Cordon, Shannon M Reilly, Chao-Wei Hung, Wenmin Xia, Peng Zhao, Martina Wallace, Denise E Lackey, Xiao-Wei Chen, Olivia Osborn, Juliane G Bogner-Strauss, Dan Theodorescu, Christian M Metallo, Jerrold M Olefsky, Alan R Saltiel
Insulin increases glucose uptake into adipose tissue and muscle by increasing trafficking of the glucose transporter Glut4. In cultured adipocytes, the exocytosis of Glut4 relies on activation of the small G protein RalA by insulin, via inhibition of its GTPase activating complex RalGAP. Here, we evaluate the role of RalA in glucose uptake in vivo with specific chemical inhibitors and by generation of mice with adipocyte-specific knockout of RalGAPB. RalA was profoundly activated in brown adipose tissue after feeding, and its inhibition prevented Glut4 exocytosis...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Soonwoong Jung, Hyeonwi Son, Chung Eun Hwang, Kye Man Cho, Sang Won Park, Hyun Joon Kim
Non-alcoholic steatosis is a common health problem worldwide due to altered food habits and life styles, and it is intimately linked with various metabolic disorders. In the present study, we investigated the molecular mechanism of Ganoderma lucidum (GL) against the development of non-alcoholic steatosis using in vivo and in vitro settings. C57BL/6 mice fed with normal diet (ND) or high fat diet (HFD) were administered GL extract or vehicle for 16 weeks. HFD feeding increased serum alanine aminotransferase level and hepatic lipid droplet, but these increases were significantly attenuated by GL...
June 15, 2018: Journal of Clinical Medicine
Chang Zhang, Yue Jiang, Jia Liu, Meina Jin, Nan Qin, Ying Chen, Wenyan Niu, Hongquan Duan
Introduction: The Chinese herb Potentilla chinensis can reduce blood glucose level of diabetic mice. Tiliroside is the main effective component, but the detailed mechanism is not clear. Skeletal muscles play an important role in whole body glucose homeostasis. Insulin and exercise/contraction stimulate glucose uptake by muscle cells via redistribution of glucose transporter GLUT4 to the cell surface. Materials and methods: We explored the effects of tiliroside derivatives on cell surface GLUT4 level (GLUT4 translocation) and the underlying mechanism in L6-GLUT4 myc muscle cells...
2018: Drug Design, Development and Therapy
Shu Yang, Mengyang Liu, Yuanli Chen, Chuanrui Ma, Lipei Liu, Buchang Zhao, Yong Wang, Xiaoju Li, Yan Zhu, Xiumei Gao, Deling Kong, Yajun Duan, Jihong Han, Xiaoxiao Yang
NaoXinTong Capsule (NXT), a Chinese medicine, is currently used to treat patients with cardiovascular and cerebrovascular diseases. Clinical observations indicate its anti-diabetic functions with unclear mechanisms. Herein, we report the effect of NXT on diabetic nephropathy (DN). Type 2 diabetic db/db mice were treated with NXT for 14 weeks. In the course of treatment, NXT reduced diabetes-increased glucose levels and improved renal functions. At the end of treatment, we found that NXT ameliorated serum lipid profiles and other biochemical parameters...
June 14, 2018: Scientific Reports
Yufan Zang, Li Fan, Jihua Chen, Ruixue Huang, Hong Qin
Capsiate, a non-pungent ingredient of CH-19 Sweet, exhibits anti-obesity effects on animals and humans. This study investigated the effects and molecular mechanism of capsiate on lipid and glucose metabolism in PA-treated HepG2 cells. Results showed that compared with the PA-alone group, 100 μM capsiate inhibited lipid accumulation, decreased TG (0.0562±0.0142 vs 0.0381±0.0055 mmol/gprot, P = 0.024) and TC (0.1087±0.0037 vs 0.0359±0.0059 mmol/gprot, P = 0.000) levels, while increased HDL-C level (0.0189±0...
June 10, 2018: Journal of Agricultural and Food Chemistry
Zakir Hossain, Guru R Valicherla, Anand P Gupta, Anees A Syed, Mohammed Riyazuddin, Sharat Chandra, Mohammad I Siddiqi, Jiaur R Gayen
Pancreastatin (PST) is an endogenous peptide which regulates glucose and lipid metabolism in liver and adipose tissues. In type 2 diabetic patients, PST level is high and plays a crucial role in the negative regulation of insulin sensitivity. Novel therapeutic agents are needed to treat the diabetes and insulin resistance (IR) against the PST action. In this regard, we have investigated the PST inhibitor peptide-8 (PSTi8) action against diabetogenic PST. PSTi8 rescued PST-induced IR in HepG2 and 3T3L1 cells...
June 7, 2018: Scientific Reports
Shahla Sohrabipour, Mohammad Reza Sharifi, Mohammadreza Sharifi, Ardeshir Talebi, Nepton Soltani
This study attempted to elucidate the possible mechanism of magnesium sulfate (MgSO4 ) administration on reducing insulin resistance in type 2 diabetic rats. Fifty wistar rats were divided into five groups: NDC was fed the normal diet, CD received high-fat diet with 35 mg/kg of streptozotocin, CD-Mg animals received MgSO4 via drinking water, CD-Ins1, and CD-Ins2 animals treated with low or high dose of insulin. Body weight and blood glucose levels were measured weekly. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT) and metabolic cage assessment were performed monthly...
June 5, 2018: Fundamental & Clinical Pharmacology
Tyler Barnes, Katie M Di Sebastiano, Filip Vlavcheski, Joe Quadrilatero, Evangelia Tsiani, Marina Mourtzakis
Various in vivo studies have investigated the insulin response that is elicited when glutamate is elevated in circulation or in a given tissue; fewer studies have investigated the effects of glutamate on glucose uptake and handling. Glutamate ingestion in humans can attenuate rises in blood glucose following a carbohydrate load in absence of increases in serum insulin concentrations. However, the underlying mechanisms have yet to be investigated. To elucidate the effects of glutamate on glucose handling in skeletal muscle tissue, differentiated rat L6 myocytes were treated with glutamate and glucose uptake was assessed by the use of [3H]-2-Deoxyglucose ([3H]-2-DG)...
May 30, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Safa Abdelgadir Mohamed Elhassan, Mayuren Candasamy, Elaine Wan Ling Chan, Subrat Kumar Bhattamisra
BACKGROUND: Autophagy is a process devoted to degrade and recycle cellular components inside mammalian cells through lysosomal system. It plays a main function in the pathophysiology of several diseases. In type 2 diabetes, works demonstrated the dual functions of autophagy in diabetes biology. Studies had approved the role of autophagy in promoting different routes for movement of integral membrane proteins to the plasma membrane. But its role in regulation of GLUT4 trafficking has not been widely observed...
May 24, 2018: Diabetes & Metabolic Syndrome
Luciana Dresseno, Alexandre Lehnen, Gabriela Teló, Ariel Silveira, Melissa M Markoski, Ubiratan F Machado, Beatriz D Schaan
We assessed the effects of a diet with flaxseed or soy nuts versus estradiol on lipid profile, insulin sensitivity, and GLUT4 expression in ovariectomized female rats. Forty-four Wistar female rats (90-days old) underwent ovariectomy were divided: C (standard diet); E (standard diet+subcutaneous 17β-estradiol pellets); L (standard diet+flaxseed+subcutaneous placebo pellets); and S (standard diet+soy nuts+subcutaneous placebo pellets). Customized diets and the insertion of pellets were started 21 days after ovariectomy, and maintained for another 21 days...
May 28, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Y Yu, Y Zhao, F Teng, J Li, Y Guan, J Xu, X Lv, F Guan, M Zhang, L Chen
OBJECTIVE: The manifestations of aging include cognitive deficits and muscular dysfunction, which are closely linked to impairment of mitochondrial biogenesis. Berberine, an isoquinoline alkaloid, presents multiple anti-diabetic pharmacological effects. Evidence has indicated that insulin resistance and cognitive impairment share the same pathogenesis, and berberine could reverse glucose metabolism abnormalities and muscle mitochondrial dysfunction induced by a high-fat diet. This study was used to investigate whether berberine could be used as an anti-aging drug to prevent cognitive deficits and muscular dysfunction in natural aging...
2018: Journal of Nutrition, Health & Aging
Junyan Jin, Yunxia Yang, Xiaoming Zhu, Dong Han, Haokun Liu, Shouqi Xie
We compared the glucose clearance ability of gibel carp CAS III (A strain) with gibel carp Dongting (DT strain). A previous study suggested that these two strains responded to insulin differently. As insulin plays an important role in glucose utilization, we hypothesized that the ability to eliminate excess glucose after a glucose load would differ between A strain and DT strain. To test this hypothesis, fasted specimens of both strains of gibel carp were injected with glucose. As expected, glucose induced hyperglycemia in both A strain and DT strain...
May 23, 2018: General and Comparative Endocrinology
Danilo C Pinto-Junior, Karolline S Silva, Maria L Michalani, Caio Y Yonamine, João V Esteves, Nelly T Fabre, Karina Thieme, Sérgio Catanozi, Maristela M Okamoto, Patricia M Seraphim, Maria L Corrêa-Giannella, Marisa Passarelli, Ubiratan F Machado
Little is known about advanced glycation end products (AGEs) participation in glucose homeostasis, a process in which skeletal muscle glucose transporter GLUT4 (Scl2a4 gene) plays a key role. This study investigated (1) the in vivo and in vitro effects of AGEs on Slc2a4/GLUT4 expression in skeletal muscle of healthy rats, and (2) the potential involvement of endoplasmic reticulum and inflammatory stress in the observed regulations. For in vivo analysis, rats were treated with advanced glycated rat albumin (AGE-albumin) for 12 weeks; for in vitro analysis, soleus muscles from normal rats were incubated with bovine AGE-albumin for 2...
May 25, 2018: Scientific Reports
Nicolas J Pillon, Scott Frendo-Cumbo, Maya R Jacobson, Zhi Liu, Paul L Milligan, Hai Hoang Bui, Juleen R Zierath, Philip J Bilan, Joseph T Brozinick, Amira Klip
Ceramides contribute to obesity-linked insulin resistance and inflammation in vivo but whether this is a cell-autonomous phenomenon is debated, particularly in muscle which dictates whole-body glucose uptake. We comprehensively analyzed lipid species produced by skeletal muscle cells in response to fatty acids and targeted inhibitors of the sphingolipid pathway, and examined the consequence to insulin resistance and pro-inflammatory pathways. L6 myotubes were incubated with BSA-adsorbed palmitate or palmitoleate in presence of myriocin, fenretinide or fumonisin B1...
May 23, 2018: Journal of Lipid Research
Masahiro Tsuchiya, Shigenori Sekiai, Hiroyasu Hatakeyama, Masashi Koide, Chayanit Chaweewannakorn, Fukie Yaoita, Koichi Tan-No, Keiichi Sasaki, Makoto Watanabe, Shunji Sugawara, Yasuo Endo, Eiji Itoi, Yoshihiro Hagiwara, Makoto Kanzaki
Metabolic immunomodulation involving IL-1 has been investigated for unfavorable metabolic effects, including obesity, but a potentially favorable role for IL-1 remains unclear. Here, we find mechanistic interactions between working skeletal muscles and locally recruited neutrophils expressing IL-1β, which supports muscle performance through priming exercise-dependent GLUT4 translocation. Thus, during exercise, both IL-1α/β-deficient and neutrophil-depleted mice similarly exhibit increased fatigability associated with impaired muscle glucose homeostasis due to GLUT4 dysregulation...
May 22, 2018: Cell Reports
Chuyan Wu, Feng Jiang, Ke Wei, Zhongli Jiang
Hyperandrogenism and hyperinsulinemia are main clinical endocrine features of PCOS. Exercise can adjust the androgen level, as well as increase the sensitivity of insulin by activating PI3K-Akt insulin signaling pathways. 5αR1 has certain effects on insulin resistance and can synthesize dihydrotestosterone by metabolizing testosterone. So 5αR1 may be the target of androgen and insulin for exercise-induced regulation. To investigate the role of 5αR1 in the PI3K-Akt signaling pathway in skeletal muscle of PCOS rats activated by exercise, fifty-four female rats were randomly divided into the PCOS group (n = 42) and the control group(n = 12)...
May 22, 2018: Scientific Reports
Jingqi Ren, Yaqiu Lin, Junni Tang, Hua Yue, Yanying Zhao
BACKGROUND/AIMS: Allograft inflammatory factor-1 (AIF-1) is an inflammatory cytokine produced mainly by macrophages within human white adipose tissue. Its expression is increased in obese subjects and positively correlated with insulin resistance. The purpose of this study is to characterize the regulatory role of AIF-1 in insulin signaling of adipocyte. METHODS: AIF-1 was over-expressed via transfection of AIF-1 cDNA into murine RAW 264.7 macrophages, and the constitutive expression of AIF-1 was decreased via transfection of targeting siRNA...
May 18, 2018: Cellular Physiology and Biochemistry
Xiaowen Duan, James Krycer, Kristen Cooke, Guang Yang, David E James, Daniel Fazakerley
Trafficking regulator of GLUT4 1 (TRARG1) was recently identified to localise to glucose transporter type 4 (GLUT4) storage vesicles (GSVs) and to positively regulate GLUT4 trafficking. Our knowledge of TRARG1 structure and membrane topology is limited to predictive models, hampering efforts to further our mechanistic understanding of how it carries out its functions. Here, we use a combination of bioinformatics prediction tools and biochemical assays to define the membrane topology of the 173-amino acid mouse TRARG1...
May 22, 2018: Biochemistry
Samaneh Mafakheri, Alexandra Chadt, Hadi Al-Hasani
Rab (Ras-related proteins in brain) GTPases are key proteins responsible for a multiplicity of cellular trafficking processes. Belonging to the family of monomeric GTPases, they are regulated by cycling between their active GTP-bound and inactive GDP-bound conformations. Despite possessing a slow intrinsic GTP hydrolysis activity, Rab proteins rely on RabGAPs (Rab GTPase-activating proteins) that catalyze GTP hydrolysis and consequently inactivate the respective Rab GTPases. Two related RabGAPs, TBC1D1 and TBC1D4 (=AS160) have been described to be associated with obesity-related traits and type 2 diabetes in both mice and humans...
May 21, 2018: Biochemical Society Transactions
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