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https://www.readbyqxmd.com/read/29702126/irbesartan-attenuates-advanced-glycation-end-products-mediated-damage-in-diabetes-associated-osteoporosis-through-the-ages-rage-pathway
#1
Yan-Zhen Cheng, Shuang-Li Yang, Ji-Yu Wang, Meng Ye, Xiao-Yun Zhuo, Li-Tao Wang, Hong Chen, Hua Zhang, Li Yang
AIMS: Diabetes-associated osteoporosis is mainly caused by the formation and accumulation of advanced glycation end products (AGEs). Angiotensin II type 1 receptor blocker (ARB) has anabolic bone effects on the physicochemical properties of the bone in diabetes. We hypothesized that ARB could inhibit AGEs-induced deleterious effects. MAIN METHODS: In this study, we chose seven-week-old Leprdb/Lepr+ (db/+) and Leprdb/Leprdb (db/db) mice. After 12 week intervention by irbesartan, the microarchitecture and mechanical strength of the bone of seven-week-old db/db mice were investigated systematically...
April 24, 2018: Life Sciences
https://www.readbyqxmd.com/read/29670283/genetic-identification-of-leptin-neural-circuits-in-energy-and-glucose-homeostases
#2
Jie Xu, Christopher L Bartolome, Cho Shing Low, Xinchi Yi, Cheng-Hao Chien, Peng Wang, Dong Kong
Leptin, a hormone produced in white adipose tissue, acts in the brain to communicate fuel status, suppress appetite following a meal, promote energy expenditure and maintain blood glucose stability1,2 . Dysregulation of leptin or its receptors (LEPR) results in severe obesity and diabetes3-5 . Although intensive studies on leptin have transformed obesity and diabetes research2,6 , clinical applications of the molecule are still limited 7 , at least in part owing to the complexity and our incomplete understanding of the underlying neural circuits...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29593575/dai-zong-fang-a-traditional-chinese-herbal-formula-ameliorates-insulin-resistance-in-db-db-mice
#3
Lili Zhu, Xiaoyun Zhu, Guibo Sun, Xiangbao Meng, Min Wang, Hanming Cui, Jialong Wang, Yadong Zhai, Ke Yang, Yang Tang, Xiaobo Sun, Ximing Liu
Intricate health problems, such as insulin resistance (IR) and its associated diseases, call for multi-targeted therapies with few side effects. Based on traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus (Zhishi), of which berberine and naringin are the main constituents. Though DZF has been clinically used for treatment of IR and metabolic syndrome for decades, its mechanism in vivo remains unknown. In the present study, we observed that both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated insulin resistance with significant improvement of oral glucose tolerance test (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic C57BL/Ksj-Lepr db -/- ( db/db ) mice...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29576852/zp2495-protects-against-myocardial-ischemia-reperfusion-injury-in-diabetic-mice-through-improvement-of-cardiac-metabolism-and-mitochondrial-function-the-possible-involvement-of-ampk-foxo3a-signal-pathway
#4
Shuang Li, Hao Wu, Dong Han, Mingming Zhang, Na Li, Weihua Yu, Dongdong Sun, Zhongchan Sun, Sai Ma, Erhe Gao, Congye Li, Min Shen, Feng Cao
Coronary heart disease patients with type 2 diabetes were subject to higher vulnerability for cardiac ischemia-reperfusion (I/R) injury. This study was designed to evaluate the impact of ZP2495 (a glucagon-GLP-1 dual-agonist) on cardiac function and energy metabolism after myocardial I/R injury in db/db mice with a focus on mitochondrial function. C57BLKS/J-lepr+ /lepr+ (BKS) and db/db mice received 4-week treatment of glucagon, ZP131 (GLP-1 receptor agonist), or ZP2495, followed by cardiac I/R injury. The results showed that cardiac function, cardiac glucose metabolism, cardiomyocyte apoptosis, cardiac mitochondrial morphology, and energetic transition were improved or ameliorated by ZP2495 to a greater extent than that of glucagon and ZP131...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29343656/crispr-cas9-mediated-generation-of-obese-and-diabetic-mouse-models
#5
Jae-Il Roh, Junghoon Lee, Seong Uk Park, Young-Shin Kang, Jaehoon Lee, Ah-Reum Oh, Dong Joon Choi, Ji-Young Cha, Han-Woong Lee
Mouse models of obesity (ob/ob) and diabetes (db/db) in which the leptin (Lep) and Leptin receptor (Lepr) genes have been mutated, respectively, have contributed to a better understanding of human obesity and type 2 diabetes and to the prevention, diagnosis, and treatment of these metabolic diseases. In this study, we report the first CRISPR-Cas9-induced Lep and Lepr KO mouse models by co-microinjection of Cas9 mRNA and sgRNAs that specifically targeted Lep or Lepr in C57BL/6J embryos. Our newly established Lep and Lepr knockout (KO) mouse models showed phenotypic disorders nearly identical to those found in ob/ob and db/db mice, such as an increase in body weight, hyperglycemia, and hepatic steatosis...
January 16, 2018: Experimental Animals
https://www.readbyqxmd.com/read/29157806/trigonelline-promotes-auditory-function-through-nerve-growth-factor-signaling-on-diabetic-animal-models
#6
Rodrigo Castañeda, Isabel Rodriguez, Youn Hee Nam, Bin Na Hong, Tong Ho Kang
BACKGROUND: Protection of cochlear function and reconstruction of neuronal networks in damaged auditory sensory structures is crucial for therapeutic treatment of diabetic hearing loss. Nerve growth factor (NGF) has been used as a novel therapeutic target to protect against the neurodegenerative effects of Diabetes Mellitus (DM). PURPOSE: We aimed to evaluate the potential effect of trigonelline (TRG) on reducing auditory damage produced by DM using NGF as a potential marker...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28969688/praziquantel-treatment-after-schistosoma-japonicum-infection-maintains-hepatic-insulin-sensitivity-and-improves-glucose-metabolism-in-mice
#7
Xiaofeng Luo, Yuxiao Zhu, Ran Liu, Jingwei Song, Fan Zhang, Wenyue Zhang, Zhipeng Xu, Min Hou, Bingya Yang, Lin Chen, Minjun Ji
BACKGROUND: Epidemiological studies in China have revealed that Schistosoma japonicum infection is inversely correlated with metabolic syndrome, even after repeated chemotherapy with praziquantel (PZQ). We investigated the effect of chronic S. japonicum infection, PZQ chemotherapy, and soluble egg antigen (SEA) treatment on whole-body metabolic homeostasis and hepatic insulin sensitivity in mouse models. RESULTS: Infection with S. japonicum was found to increase whole-body and hepatic insulin sensitivity in mice...
October 2, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28954992/nonconcordant-regulation-of-mitochondrial-respiratory-complexes-in-the-kidneys-of-5-6-nephrectomized-mice
#8
Yukie Nakashita, Tomoya Sano, Hiroaki Yoshioka, Tomoki Shimada, Ryotaro Hori, Makoto Usami, Yasuhiro Hamada
Hyperglycemia induces nonconcordant regulation of renal mitochondrial respiratory complexes, increases oxidative stress, and causes diabetic nephropathy. Hypertension is a complication associated with diabetes and involves glomerular hyperfiltration, the effects of which on mitochondrial respiratory complexes are not well understood. To investigate the effect of glomerular hyperfiltration on renal mitochondrial respiratory complexes, we used the 5/6 nephrectomized BKS. Cg-Dock7(m)+/+Lepr(db)/J, Dock7(m)+/+Lepr(db) mice (db/m-5/6Nx mice) as a model for glomerular hyperfiltration...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28938561/preventive-effects-of-the-sodium-glucose-cotransporter-2-inhibitor-tofogliflozin-on-diethylnitrosamine-induced-liver-tumorigenesis-in-obese-and-diabetic-mice
#9
Koki Obara, Yohei Shirakami, Akinori Maruta, Takayasu Ideta, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Takuji Tanaka, Mitsuru Seishima, Masahito Shimizu
Sodium glucose cotransporter 2 inhibitors are expected to ameliorate the abnormalities associated with metabolic syndrome including non-alcoholic fatty liver disease. In this study, we investigated the effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty liver disease-related liver tumorigenesis in C57BL/KsJ-+Lepr (db) /+Lepr (db) obese and diabetic mice. The direct effects of tofogliflozin on human liver cancer cell proliferation were also evaluated...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28893589/leptin-status-alters-buprenorphine-induced-antinociception-in-obese-mice-with-dysfunctional-leptin-receptors
#10
Zachary Glovak, Sara Mihalko, Helen A Baghdoyan, Ralph Lydic
Buprenorphine is an opiate used for pain management and to treat opiate addiction. The cytokine leptin can modulate nociception, but the extent to which buprenorphine-induced antinociception varies as a function of leptin signaling has not been characterized. Four congenic mouse lines with phenotypes that include differences in body weight and leptin status were used to test the hypothesis that the antinociceptive effects of buprenorphine vary as function of sex and leptin signaling. Each mouse line was comprised of males (n=12) and females (n=12) for a total of 96 animals...
November 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28885548/novel-insights-into-the-adipokinome-of-obese-and-obese-diabetic-mouse-models
#11
Birgit Knebel, Simon Goeddeke, Gereon Poschmann, Daniel F Markgraf, Sylvia Jacob, Ulrike Nitzgen, Waltraud Passlack, Christina Preuss, Hans-Dieter Dicken, Kai Stühler, Sonja Hartwig, Stefan Lehr, Jorg Kotzka
The group of adipokines comprises hundreds of biological active proteins and peptides released from adipose tissue. Alterations of those complex protein signatures are suggested to play a crucial role in the pathophysiology of multifactorial, metabolic diseases. We hypothesized that also the pathophysiology of type-2-diabetes is linked to the dysregulation of the adipocyte secretome. To test this, we investigated mouse models with monogenic defects in leptin signaling which are susceptible to adipositas (C57BL/6 Cg-Lep(ob) (obob)) or adipositas with diabetes (C57BL/KS Cg-Lepr(db) (dbdb)) according to their genetic background...
September 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28865861/liver-transcriptome-analysis-reveals-important-factors-involved-in-the-metabolic-adaptation-of-the-transition-cow
#12
N-T Ha, C Drögemüller, C Reimer, F Schmitz-Hsu, R M Bruckmaier, H Simianer, J J Gross
During early lactation, dairy cows experience a severe metabolic load often resulting in the development of various diseases. The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. We conducted a whole-liver transcriptome analysis for the transition cow to identify novel factors crucial for metabolic adaptation. Liver samples were obtained from 6 Red Holstein dairy cows (parity 2 to 7, mean ± standard deviation: 3...
November 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28852138/inhibition-of-gdf8-myostatin-accelerates-bone-regeneration-in-diabetes-mellitus-type-2
#13
Christoph Wallner, Henriette Jaurich, Johannes Maximilian Wagner, Mustafa Becerikli, Kamran Harati, Mehran Dadras, Marcus Lehnhardt, Björn Behr
Metabolic diseases like diabetes mellitus cause bone healing deficiencies. We found significant impairment of bone regeneration, osteogenic differentiation and proliferation in diabetic bone. Moreover recent studies suggest a highly underestimated importance of GDF8 (Myostatin) in bone metabolism. Our goal was to analyze the role of GDF8 as a regulator of osteogenic differentiation, proliferation and bone regeneration. We used a murine tibial defect model in diabetic (Lepr(db-/-)) mice. Myostatin-Inhibitor Follistatin was administered in tibial bony defects of diabetic mice...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793909/-6-gingerol-from-zingiber-officinale-potentiates-glp-1-mediated-glucose-stimulated-insulin-secretion-pathway-in-pancreatic-%C3%AE-cells-and-increases-rab8-rab10-regulated-membrane-presentation-of-glut4-transporters-in-skeletal-muscle-to-improve-hyperglycemia-in
#14
Mehdi Bin Samad, Md Nurul Absar Bin Mohsin, Bodiul Alam Razu, Mohammad Tashnim Hossain, Sinayat Mahzabeen, Naziat Unnoor, Ishrat Aklima Muna, Farjana Akhter, Ashraf Ul Kabir, J M A Hannan
BACKGROUND: [6]-Gingerol, a major component of Zingiber officinale, was previously reported to ameliorate hyperglycemia in type 2 diabetic mice. Endocrine signaling is involved in insulin secretion and is perturbed in db/db Type-2 diabetic mice. [6]-Gingerol was reported to restore the disrupted endocrine signaling in rodents. In this current study on Lepr(db/db) diabetic mice, we investigated the involvement of endocrine pathway in the insulin secretagogue activity of [6]-Gingerol and the mechanism(s) through which [6]-Gingerol ameliorates hyperglycemia...
August 9, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28580288/restoration-of-lepr-in-%C3%AE-cells-of-lepr-null-mice-does-not-prevent-hyperinsulinemia-and-hyperglycemia
#15
Anna M D'souza, Timothy J Kieffer
OBJECTIVE: The adipose-derived hormone leptin plays an important role in regulating body weight and glucose homeostasis. Leptin receptors are expressed in the central nervous system as well as peripheral tissues involved in regulating glucose homeostasis, including insulin-producing β cells of the pancreas. Previous studies assessing the role of leptin receptors in β cells used Cre-loxP to disrupt the leptin receptor gene (Lepr) in β cells, but variable results were obtained. Furthermore, recombination of Lepr was observed in the hypothalamus or exocrine pancreas, in addition to the β cells, and Lepr in non-β cells may have compensated for the loss of Lepr in β cells, thus making it difficult to assess the direct effects of Lepr in β cells...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28577176/complement-c5a-induces-mesenchymal-stem-cell-apoptosis-during-the-progression-of-chronic-diabetic-complications
#16
Ming Zhu, Xiao He, Xiao-Hui Wang, Wei Qiu, Wei Xing, Wei Guo, Tian-Chen An, Luo-Quan Ao, Xue-Ting Hu, Zhan Li, Xiao-Ping Liu, Nan Xiao, Jian Yu, Hong Huang, Xiang Xu
AIMS/HYPOTHESIS: Regeneration and repair mediated by mesenchymal stem cells (MSCs) are key self-protection mechanisms against diabetic complications, a reflection of diabetes-related cell/tissue damage and dysfunction. MSC abnormalities have been reported during the progression of diabetic complications, but little is known about whether a deficiency in these cells plays a role in the pathogenesis of this disease. In addition to MSC resident sites, peripheral circulation is a major source of MSCs that participate in the regeneration and repair of damaged tissue...
September 2017: Diabetologia
https://www.readbyqxmd.com/read/28438610/hyperglycemia-increases-interstitial-cells-of-cajal-via-mapk1-and-mapk3-signaling-to-etv1-and-kit-leading-to-rapid-gastric-emptying
#17
Yujiro Hayashi, Yoshitaka Toyomasu, Siva Arumugam Saravanaperumal, Michael R Bardsley, John A Smestad, Andrea Lorincz, Seth T Eisenman, Gianluca Cipriani, Molly H Nelson Holte, Fatimah J Al Khazal, Sabriya A Syed, Gabriella B Gajdos, Kyoung Moo Choi, Gary J Stoltz, Katie E Miller, Michael L Kendrick, Brian P Rubin, Simon J Gibbons, Adil E Bharucha, David R Linden, Louis James Maher, Gianrico Farrugia, Tamas Ordog
BACKGROUND & AIMS: Depletion of interstitial cells of Cajal (ICCs) is common in diabetic gastroparesis. However, in approximately 20% of patients with diabetes, gastric emptying (GE) is accelerated. GE also occurs faster in obese individuals, and is associated with increased blood levels of glucose in patients with type 2 diabetes. To understand the fate of ICCs in hyperinsulinemic, hyperglycemic states characterized by rapid GE, we studied mice with mutation of the leptin receptor (Leprdb/db ), which in our colony had accelerated GE...
August 2017: Gastroenterology
https://www.readbyqxmd.com/read/28381495/dietary-reversal-of-neuropathy-in-a-murine-model-of-prediabetes-and-metabolic-syndrome
#18
Lucy M Hinder, Phillipe D O'Brien, John M Hayes, Carey Backus, Andrew P Solway, Catrina Sims-Robinson, Eva L Feldman
Patients with metabolic syndrome, which is defined as obesity, dyslipidemia, hypertension and impaired glucose tolerance (IGT), can develop the same macro- and microvascular complications as patients with type 2 diabetes, including peripheral neuropathy. In type 2 diabetes, glycemic control has little effect on the development and progression of peripheral neuropathy, suggesting that other metabolic syndrome components may contribute to the presence of neuropathy. A parallel phenomenon is observed in patients with prediabetes and metabolic syndrome, where improvement in weight and dyslipidemia more closely correlates with restoration of nerve function than improvement in glycemic status...
June 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28256636/elevated-fibroblast-growth-factor-21-fgf21-in-obese-insulin-resistant-states-is-normalised-by-the-synthetic-retinoid-fenretinide-in-mice
#19
Nicola Morrice, George D Mcilroy, Seshu R Tammireddy, Jennifer Reekie, Kirsty D Shearer, Mary K Doherty, Mirela Delibegović, Phillip D Whitfield, Nimesh Mody
Fibroblast growth factor 21 (FGF21) has emerged as an important beneficial regulator of glucose and lipid homeostasis but its levels are also abnormally increased in insulin-resistant states in rodents and humans. The synthetic retinoid Fenretinide inhibits obesity and improves glucose homeostasis in mice and has pleotropic effects on cellular pathways. To identify Fenretinide target genes, we performed unbiased RNA-seq analysis in liver from mice fed high-fat diet ± Fenretinide. Strikingly, Fgf21 was the most downregulated hepatic gene...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194019/il-25-stimulates-m2-macrophage-polarization-and-thereby-promotes-mitochondrial-respiratory-capacity-and-lipolysis-in-adipose-tissues-against-obesity
#20
Juan Feng, Lingyi Li, Zhiying Ou, Qiao Li, Baoyong Gong, Zhenxian Zhao, Weiwei Qi, Ti Zhou, Jun Zhong, Weibin Cai, Xia Yang, Aiping Zhao, Guoquan Gao, Zhonghan Yang
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr-/-) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD)...
February 13, 2017: Cellular & Molecular Immunology
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