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Muthukumaran Padmanaban, Thiyagarajan Gopal, Arun Babu Rajendran, Baddireddi Subhadra Lakshmi
Among several metabolic disorders, the pathogenesis of insulin resistance is considered to be multifactorial. Raffinose, an oligosaccharide isolated from the rhizome of Costus speciosus showed ≤50% inhibition of lipid accumulation in differentiated HepG2 and 3T3-L1 cells through exhibiting partial agonism to PPARγ, and, an enhanced secretion of adiponectin in 3T3-L1 adipocytes. Raffinose was also observed to attenuate the expression of SREBP1c, ACC and FAS which are involved in the fatty acid synthesis. A corresponding upregulation of PPARα and ACO involved in fatty acid oxidation was observed in steatotic HepG2 hepatocytes and 3T3-L1 adipocytes...
February 16, 2018: Chemico-biological Interactions
Ayodele Olufemi Morakinyo, Titilola Aderonke Samuel, Daniel Abiodun Adekunbi
OBJECTIVE: We investigated the effects of magnesium supplementation on glucose tolerance, insulin sensitivity, oxidative stress as well as the concentration of insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced type-2 diabetic (T2D) rats. METHODS: Rats were divided into four groups designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet (Mg2-D)...
January 1, 2018: Endocrine Regulations
Outi Huttala, Maaria Palmroth, Pauliina Hemminki, Tarja Toimela, Tuula Heinonen, Timo Ylikomi, Jertta-Riina Sarkanen
Many adipose tissue-related diseases, such as obesity and type 2 diabetes, are worldwide epidemics. For studying these diseases, relevant human cell models are needed. In this study, we developed a vascularized adipose tissue model where human adipose stromal cells (hASC) and human umbilical cord vein endothelial cells (HUVEC) were co-cultured with natural adipogenic and defined serum-free angiogenic media for 14 days. Several different protocols were compared to each other. The protocols varied in cell numbers and plating sequences...
February 14, 2018: Basic & Clinical Pharmacology & Toxicology
Ri-Su Na, Cong Ma, Qiao-Rui Liu, Li-Ming Wu, Xu-Lei Zheng, Zhi-Wen Liu
The primarily metabolic abnormality in type 2 diabetes mellitus (T2DM) is the defect in gluconeogenesis and glucose uptake. Itraconazole (ITCZ) is a traditional azole drug with anti-fungal and anticancer properties. However, limited attention has been directed towards the contribution of ITCZ to hepatic gluconeogenesis and glucose uptake in T2DM. The present study aimed to investigate the potential effects of ITCZ on hepatic gluconeogenesis and glucose uptake as well as the underlying mechanisms. No obvious change in cell viability was detected by MTT assay in HepG2 cells with ITCZ treatment at gradually increasing concentrations...
February 2018: Experimental and Therapeutic Medicine
Sevda Gheibi, Sajad Jeddi, Mattias Carlström, Hanieh Gholami, Asghar Ghasemi
PURPOSE: Supplementation with inorganic nitrate to boost the nitrate-nitrite-nitric oxide (NO) pathway, may act as a potential therapeutic agent in diabetes. The aim of this study was to determine the effects of nitrate on carbohydrate metabolism, lipid profiles, oxidative stress, and inflammation in obese type 2 diabetic rats. METHODS: Male Wistar rats were divided into 4 groups: Control, control + nitrate, diabetes, and diabetes + nitrate. Diabetes was induced using a high-fat diet and low-dose of streptozotocin...
February 10, 2018: Nitric Oxide: Biology and Chemistry
Shanthi Ganesan, Corey M Summers, Sarah C Pearce, Nicholas K Gabler, Rudy J Valentine, Lance H Baumgard, Robert P Rhoads, Joshua T Selsby
Heat-related complications continue to be a major health concern for humans and animals and lead to potentially life-threatening conditions. Heat stress (HS) alters metabolic parameters and may alter glucose metabolism and insulin signaling. Therefore, the purpose of this investigation was to determine the extent to which 12 h of HS altered energetic metabolism in oxidative skeletal muscle. To address this, crossbred gilts (n=8/group) were assigned to one of three environmental treatments for 12 h: thermoneutral (TN; 21° C), heat stress (HS; 37° C), or pair-fed to HS counterparts but housed in TN conditions (PFTN)...
February 8, 2018: Journal of Animal Science
Duy Trong Vien Diep, Kyungki Hong, Triyeng Khun, Mei Zheng, Asad Ul-Haq, Hee-Sook Jun, Young-Bum Kim, Kwang-Hoon Chun
Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adipogenesis in 3T3-L1 cells. Here, we show that KD025 (formerly known as SLx-2119), a ROCK2-specific inhibitor, suppresses adipogenesis in 3T3-L1 cells partially through a ROCK2-independent mechanism. KD025 downregulated the expression of key adipogenic transcription factors PPARγ and C/EBPα during adipogenesis in addition to lipogenic factors FABP4 and Glut4...
February 6, 2018: Scientific Reports
M Varela-Guruceaga, F I Milagro, J A Martínez, C de Miguel
Obesity is characterized by hypertrophy and hyperplasia of adipose tissue, which have been related to the development of hypoxia and insulin resistance. On the other hand, caveolin-1 (Cav-1), one of the main proteins of caveolae, promotes insulin receptor (IR) phosphorylation and the subsequent activation of insulin signaling. In this work we investigated the effect of hypoxia on Cav-1 regulation and the status of insulin signaling in 3T3-L1 adipocytes. Our results showed that hypoxia inhibited adipogenesis and insulin signaling in adipocytes...
January 30, 2018: Molecular and Cellular Endocrinology
E Coudert, C Praud, J Dupont, S Crochet, E Cailleau-Audouin, T Bordeau, E Godet, A Collin, C Berri, S Tesseraud, S Métayer-Coustard
Glucose transport into cells is the first limiting step for the regulation of glucose homeostasis. In mammals, it is mediated by a family of facilitative glucose transporters (GLUTs) (encoded by SLC2A* genes), with a constitutive role (GLUT1), or insulin-sensitive transporters (GLUT4, GLUT8 and GLUT12). Compared to mammals, the chicken shows high levels of glycaemia and relative insensitivity to exogenous insulin. To date, only GLUT1, -8 and -12 have been described in chicken skeletal muscles but not fully characterized, whereas GLUT4 was reported as lacking...
February 1, 2018: Journal of Animal Science
Khanh-Van Tran, Timothy Fitzgibbons, So Yun Min, Tiffany DeSouza, Silvia Corvera
OBJECTIVE: Perivascular adipose tissue depots around the aorta are regionally distinct and have specific functional properties. Thoracic aorta perivascular adipose tissue (tPVAT) expresses higher levels of thermogenic genes and lower levels of inflammatory genes than abdominal aorta perivascular adipose tissue (aPVAT). It is not known whether this distinction is due to the in-vivo functional environment or to cell-autonomous traits that persist outside the in-vivo setting. In this study, we asked whether the progenitor cells in tPVAT and aPVAT have cell-autonomous traits that lead to formation of regionally distinct PVAT...
January 10, 2018: Molecular Metabolism
Juncheng Zhuo, Qiaohuang Zeng, Dake Cai, Xiaohui Zeng, Yuxing Chen, Haining Gan, Xuejun Huang, Nan Yao, Dane Huang, Chengzhe Zhang
Type 2 diabetic mellitus (T2DM), which is characterized by insulin resistance (IR), hyperglycemia and hyperlipidemia, is a comprehensive dysfunction of metabolism. The insulin receptor (INSR)/phosphoinositide 3‑kinase (PI3K)/AKT signaling pathway is well acknowledged as a predominant pathway associated with glucose uptake; however, the effect of streptozotocin (STZ) plus a high fat and sugar diet (HFSD) on the proteins associated with this pathway requires further elucidation. In order to explore this effect, a T2DM rat model was constructed to investigate T2DM pathogenesis and potential therapeutic advantages...
January 26, 2018: Molecular Medicine Reports
Woojung Lee, Hyo Jung Lee, Han Byul Jang, Hyo-Jin Kim, Hyo-Jeong Ban, Kwang Youl Kim, Moon Suk Nam, Joo Sun Choi, Kyung-Tae Lee, Seong Beom Cho, Sang Ick Park, Hye-Ja Lee
To unravel metabolic determinats of insulin resistance, we performed a targeted metabolomics analysis in Korean Children-Adolescent Cohort Study (KoCAS, n = 430). Sixty-seven metabolites were associated with insulin resistance in adolescents and the association also found in an adult population (KoGES, n = 2,485). Functional interactions of metabolites with gene/proteins using biological pathway with insulin resistance were not identified biological significance and regulatory effects of asymmetric dimethylarginine (ADMA)...
February 1, 2018: Scientific Reports
Ling Chen, Xing-Yun Wang, Jin-Gai Zhu, Liang-Hui You, Xing Wang, Xian-Wei Cui, Chun-Mei Shi, Fang-Yan Huang, Ya-Hui Zhou, Lei Yang, Ling-Xia Pang, Yao Gao, Chen-Bo Ji, Xi-Rong Guo
The novel obesity-associated protein Phosphotyrosine Interaction Domain containing 1 (PID1) inhibits insulin-PI3K/Akt signaling pathway and insulin-stimulated glucose uptake in vitro. In this study, we generated fat tissue-specific aP2-PID1 transgenic (aP2-PID1tg) mice and PID1 knockout (PID1-/-) mice to explore how PID1 affects glucose metabolism in vivo. We observed insulin resistance and impaired insulin-PI3K/Akt signaling in aP2-PID1tg mice. Consistent with these data, the PID1-/- mice displayed improved glucose tolerance and insulin sensitivity under chow diet, with increased Akt phosphorylation in white adipose tissue (WAT)...
January 29, 2018: Biochimica et Biophysica Acta
Shahla Sohrabipour, Mohammad Reza Sharifi, Ardeshir Talebi, Mohammadreza Sharifi, Nepton Soltani
Skeletal muscle, hepatic insulin resistance, and beta cell dysfunction are the characteristic pathophysiological features of type 2 diabetes mellitus. GABA has an important role in pancreatic islet cells. The present study attempted to clarify the possible mechanism of GABA to improve glucose tolerance in a model of type 2 diabetes mellitus in rats. Fifty Wistar rats were divided into five groups: NDC that was fed the normal diet, CD which received a high-fat diet with streptozotocin, CD-GABA animals that received GABA via intraperitoneal injection, plus CD-Ins1 and CD-Ins2 groups which were treated with low and high doses of insulin, respectively...
January 29, 2018: European Journal of Pharmacology
Joanna Szydlarska, Christine Weiss, Krzysztof Marycz
Methyl-β-cyclodextrin (MβCD) is a cyclic oligosaccharide, commonly used as a pharmacological agent to deplete membrane cholesterol. In this study, we examined the effect of MβCD on adipose-derived mesenchymal stromal cells (ASCs) isolated form healthy horses (ASCCTRL) and from horses suffering from metabolic syndrome (ASCEMS). We investigated the changes in the mRNA levels of the glucose transporter 4 (GLUT4) and found that MβCD application may lead to a significant improvement in glucose transport in ASCEMS...
January 30, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Mark C Turner, Darren J Player, Neil R W Martin, Elizabeth C Akam, Mark P Lewis
Skeletal muscle is an insulin sensitive tissue and accounts for approximately 80% of post-prandial glucose disposal. This study describes the effects of insulin, delivered for 72 hours, to skeletal muscle myoblasts during differentiation or to skeletal muscle myotubes. After chronic treatment, cultures were acutely stimulated with insulin and analysed for total and phosphorylated Akt (Ser473 ), mRNA expression of metabolic and myogenic markers and insulin-stimulated glucose uptake. Skeletal muscle cells differentiated in the presence of insulin chronically, reduced acute insulin stimulated phosphorylation of Akt Ser473 ...
January 31, 2018: Journal of Cellular Biochemistry
Abu Sadat Md Sayem, Aditya Arya, Hamed Karimian, Narendiran Krishnasamy, Ameya Ashok Hasamnis, Chowdhury Faiz Hossain
Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and facilitate the rapid insulin-dependent storage of glucose in muscle and fat cells...
January 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Raphael Taiwo Aruleba, Tayo Alex Adekiya, Babatunji Emmanuel Oyinloye, Abidemi Paul Kappo
Presently, many studies have focused on exploring in silico approaches in the identification and development of alternative therapy for the treatment and management of cancer. Solute carrier family-2-member-4-gene (Slc2a4) which encodes glucose transporter 4 protein (GLUT4), has been identified as a promising therapeutic target for cancer. Though Slc2a4 is known to play a major regulatory role in the pathophysiology of type 2 diabetes, emerging evidence suggests that successful pharmacological inhibition of this protein may lead to the development of a novel drug candidate for the treatment of cancer...
January 28, 2018: International Journal of Molecular Sciences
Ana Catarina R G Fonseca, Eugénia Carvalho, Jan W Eriksson, Maria J Pereira
Calcineurin inhibitors are used in immunosuppressive therapy applied after transplantation, but they are associated with major metabolic side effects including the development of new onset diabetes. Previously, we have shown that the calcineurin inhibiting drugs tacrolimus and cyclosporin A reduce adipocyte and myocyte glucose uptakes by reducing the amount of glucose transporter type 4 (GLUT4) at the cell surface, due to an increased internalization rate. However, this happens without alteration in total protein and phosphorylation levels of key proteins involved in insulin signalling or in the total amount of GLUT4...
January 27, 2018: Molecular and Cellular Biochemistry
Tatsuya Kondo, Miwa Nakamura, Sayaka Kitano, Junji Kawashima, Takeshi Matsumura, Takashi Ohba, Munekage Yamaguchi, Hidetaka Katabuchi, Eiichi Araki
BACKGROUND: Gestational diabetes insipidus (GDI) is a rare endocrine complication during pregnancy that is associated with vasopressinase overproduction from the placenta. Although increased vasopressinase is associated with placental volume, the regulation of placental growth in the later stage of pregnancy is not well known. CASE PRESENTATION: A 16-year-old pregnant woman was urgently transferred to our hospital because of threatened premature labor when the Kumamoto earthquakes hit the area where she lived...
January 30, 2018: BMC Endocrine Disorders
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