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https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#1
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29341865/evidence-of-genetic-predisposition-for-metabolically-healthy-obesity-and-metabolically-obese-normal-weight
#2
Lam Opal Huang, Ruth Loos, Tuomas Oskari Kilpeläinen
Obesity has evolved into a global pandemic, which constitutes a major threat to public health. The majority of obesity-related health care costs are due to cardiometabolic complications, such as insulin resistance, dyslipidemia, and hypertension, which are risk factors for type 2 diabetes and cardiovascular disease. However, many obese individuals, often called metabolically healthy obese (MHO), seem to be protected from these cardiometabolic complications. Conversely, there is a group of individuals who suffer from cardiometabolic complications despite being of normal weight; a condition termed metabolically obese normal weight (MONW)...
December 20, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29341443/stachyose-improves-inflammation-through-modulating-gut-microbiota-of-high-fat-diet-streptozotocin-induced-type-2-diabetes-in-rats
#3
Guimei Liu, Jia Bei, Li Liang, Guoyong Yu, Lu Li, Quanhong Li
SCOPE: The present study was undertaken to assess the effects of stachyose (STS) on type 2 diabetes in rats, and changes in the gut microbiota compared to metformin (MET). METHODS AND RESULTS: The type 2 diabetic model was successfully established via a high-fat diet (HFD) / streptozotocin (STZ) in Wistar rats, and STS or MET was administered for 4 weeks. Blood was collected to analyze biochemical parameters, pancreas for mRNA expression of related gene and contents of colon for gut microbiota...
January 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29341416/resveratrol-influences-pancreatic-islets-by-opposing-effects-on-electrical-activity-and-insulin-release
#4
Simone Brouwer, Theresa Hoffmeister, Anne Gresch, Lisa Schönhoff, Martina Düfer
SCOPE: Resveratrol is suggested to improve glycemic control by activation of sirtuin 1 (SIRT1) and has already been tested clinically. Our investigation characterizes the targets of resveratrol in pancreatic beta cells and their contribution to short- and long-term effects on insulin secretion. METHODS AND RESULTS: Islets or beta cells were isolated from C57Bl/6N mice. Electrophysiology was performed with microelectrode arrays and patch-clamp technique, insulin secretion and content were determined by radioimmunoassay, cAMP was measured by enzyme-linked immunosorbent assay and cytosolic Ca2+ concentration by fluorescence methods...
January 17, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29338566/constructing-heparin-modified-pancreatic-decellularized-scaffold-to-improve-its-re-endothelialization
#5
Liancheng Xu, Yibing Guo, Yan Huang, Yicheng Xiong, Yang Xu, Xiaohong Li, Jingjing Lu, Lei Wang, Yao Wang, Yuhua Lu, Zhiwei Wang
Pancreas transplantation is considered as a promising therapeutic option with the potential to cure diabetes. However, efficacy of current clinical transplantation is limited by the donor organ. With regard to creating a functional pancreas-tissue equivalent for transplantation, vascularization remains a large obstacle. To enhance the angiogenic properties of pancreatic decellularized scaffold, surface modification of the vasculature was used to promote endothelialization efficiency. In this study, an endothelialized pancreatic decellularized scaffold was obtained through heparin modification under mild conditions...
January 1, 2018: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/29337308/rage-binds-preamyloid-iapp-intermediates-and-mediates-pancreatic-%C3%AE-cell-proteotoxicity
#6
Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P Raleigh, Ann Marie Schmidt
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337057/heterogeneity-of-autophagic-status-in-pancreatic-%C3%AE-cells-under-metabolic-stress
#7
Mai Kamitani, Takeshi Miyatsuka, Masaki Miura, Kosuke Azuma, Luka Suzuki, Miwa Himuro, Takehiro Katahira, Yuya Nishida, Yoshio Fujitani, Hirotaka Watada
Autophagy in β cells has been demonstrated to play a pivotal role in cellular homeostasis and the progression of glucose intolerance. Although autophagic activity is affected by metabolic stress both in vivo and in vitro, it remains unclear as to what extent the autophagic status in each β cell is different from its neighboring cells. To address this question, GFP-LC3 reporter mice, which can visualize the autophagic status of each β cell as green-fluorescent puncta, were crossed with obese diabetic db/db mice...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29334743/-adiponectin-in-patients-with-metabolic-syndrome-and-diseases-of-the-liver-bile-ducts-and-pancreas
#8
Adam Vašura, Martin Blaho, Petr Dítě, Tomáš Kupka, Pavel Svoboda, Arnošt Martínek
Epidemiological data show that the metabolic syndrome can be diagnosed in up to 30 % of the population. Regarding 5 components of the metabolic syndrome, three of them, in case of positivity (visceral obesity, arterial hypertension, hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes mellitus), are pathogenic factors which are the most frequently related to cardiovascular diseases, but currently they are also the focus of interest for gastroenterologists. The relationship between non-alcoholic hepatic steatosis, including non-alcoholic steatohepatitis, has been described...
2018: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29333379/broccoli-brassica-oleracea-reduces-oxidative-damage-to-pancreatic-tissue-and-combats-hyperglycaemia-in-diabetic-rats
#9
Sithara Suresh, Mostafa Ibrahim Waly, Mohammad Shafiur Rahman, Nejib Guizani, Mohamed Abdullah Badar Al-Kindi, Halima Khalfan Ahmed Al-Issaei, Sultan Nasser Mohd Al-Maskari, Bader Rashid Said Al-Ruqaishi, Ahmed Al-Salami
Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli (Brassica oleracea) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats...
December 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/29333267/type-1-diabetes-genome-wide-association-studies-not-to-be-lost-in-translation
#10
REVIEW
Flemming Pociot
Genetic studies have identified >60 loci associated with the risk of developing type 1 diabetes (T1D). The vast majority of these are identified by genome-wide association studies (GWAS) using large case-control cohorts of European ancestry. More than 80% of the heritability of T1D can be explained by GWAS data in this population group. However, with few exceptions, their individual contribution to T1D risk is low and understanding their function in disease biology remains a huge challenge. GWAS on its own does not inform us in detail on disease mechanisms, but the combination of GWAS data with other omics-data is beginning to advance our understanding of T1D etiology and pathogenesis...
December 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29333050/improvement-of-insulin-secretion-and-pancreatic-%C3%AE-cell-function-in-streptozotocin-induced-diabetic-rats-treated-with-aloe-vera-extract
#11
Ayesha Noor, S Gunasekaran, M A Vijayalakshmi
Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Plant extracts and their products are being used as an alternative system of medicine for the treatment of diabetes. Aloe vera has been traditionally used to treat several diseases and it exhibits antioxidant, anti-inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar diabetic rats were used in this study to understand the potential protective effect of A. vera extract on the pancreatic islets...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29330559/a-post-translational-balancing-act-the-good-and-the-bad-of-sumoylation-in-pancreatic-islets
#12
EDITORIAL
Patrick E MacDonald
Post-translational modification of proteins contributes to the control of cell function and survival. The balance of these in insulin-producing pancreatic beta cells is important for the maintenance of glucose homeostasis. Protection from the damaging effects of reactive oxygen species is required for beta cell survival, but if this happens at the expense of insulin secretory function then the ability of islets to respond to changing metabolic conditions may be compromised. In this issue of Diabetologia, He et al ( https://doi...
January 12, 2018: Diabetologia
https://www.readbyqxmd.com/read/29330461/comparing-olive-oil-and-c4-dietary-oil-a-prodrug-for-the-gpr119-agonist-2-oleoyl-glycerol-less-energy-intake-of-the-latter-is-needed-to-stimulate-incretin-hormone-secretion-in-overweight-subjects-with-type-2-diabetes
#13
Mette Johannsen Mandøe, Katrine Bagge Hansen, Johanne Agerlin Windeløv, Filip Krag Knop, Jens Frederik Rehfeld, Mette Marie Rosenkilde, Jens Juul Holst, Harald Severin Hansen
BACKGROUND/OBJECTIVE: After digestion, dietary triacylglycerol stimulates incretin release in humans, mainly through generation of 2-monoacylglycerol, an agonist for the intestinal G protein-coupled receptor 119 (GPR119). Enhanced incretin release may have beneficial metabolic effects. However, dietary fat may promote weight gain and should therefore be restricted in obesity. We designed C4-dietary oil (1,3-di-butyryl-2-oleoyl glycerol) as a 2-oleoyl glycerol (2-OG)-generating fat type, which would stimulate incretin release to the same extent while providing less calories than equimolar amounts of common triglycerides, e...
January 12, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29330456/20-hete-promotes-glucose-stimulated-insulin-secretion-in-an-autocrine-manner-through-ffar1
#14
Sorin Tunaru, Remy Bonnavion, Isabell Brandenburger, Jens Preussner, Dominique Thomas, Klaus Scholich, Stefan Offermanns
The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic β-cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote glucose-stimulated insulin secretion (GSIS). However, the physiological role of FFAR1 in β-cells remains poorly understood. Here we show that 20-HETE activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than dietary fatty acids such as palmitic, linoleic, and α-linolenic acid. Murine and human β-cells produce 20-HETE, and the ω-hydroxylase-mediated formation and release of 20-HETE is strongly stimulated by glucose...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29329392/risk-of-pancreatic-cancer-associated-with-family-history-of-cancer-and-other-medical-conditions-by-accounting-for-smoking-among-relatives
#15
E Molina-Montes, P Gomez-Rubio, M Márquez, M Rava, M Löhr, C W Michalski, X Molero, A Farré, J Perea, W Greenhalf, L Ilzarbe, M O'Rorke, A Tardón, T Gress, V M Barberà, T Crnogorac-Jurcevic, E Domínguez-Muñoz, L Muñoz-Bellvís, J Balsells, E Costello, J Huang, M Iglesias, J Kleeff, Bo Kong, J Mora, L Murray, D O'Driscoll, I Poves, A Scarpa, W Ye, M Hidalgo, L Sharp, A Carrato, F X Real, N Malats
Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR)...
January 10, 2018: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29329158/expression-of-gastrin-family-peptides-in-pancreatic-islets-and-their-role-in-%C3%AE-cell-function-and-survival
#16
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
OBJECTIVES: Modulation of cholecystokinin (CCK) receptors has been shown to influence pancreatic endocrine function. METHODS: We assessed the impact of the CCKA and CCKB receptor modulators, (pGlu-Gln)-CCK-8 and gastrin-17, respectively, on β-cell secretory function, proliferation and apoptosis and glucose tolerance, and investigating alterations of CCK and gastrin islet expression in diabetes. RESULTS: Initially, the presence of CCK and gastrin, and expression of their receptors were evidenced in β-cell lines and mouse islets...
January 12, 2018: Pancreas
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#17
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29323186/combination-of-high-fat-high-fructose-diet-and-low-dose-streptozotocin-to-model-long-term-type-2-diabetes-complications
#18
David André Barrière, Christophe Noll, Geneviève Roussy, Farah Lizotte, Anissa Kessai, Karyn Kirby, Karine Belleville, Nicolas Beaudet, Jean-Michel Longpré, André C Carpentier, Pedro Geraldes, Philippe Sarret
The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose consumption. Here, we thus combined high-fat/high-fructose diet, with multiple low-dose injections of streptozotocin (HF/HF/Stz) to emulate the long-term complications of T2DM. HF/HF/Stz rats, monitored over 56 weeks, exhibited metabolic dysfunctions associated with the different stages of the T2DM disease progression in humans: an early prediabetic phase characterized by an hyperinsulinemic period with modest dysglycemia, followed by a late stage of T2DM with frank hyperglycemia, normalization of insulinemia, marked dyslipidemia, hepatic fibrosis and pancreatic β-cell failure...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322773/sers-based-label-free-insulin-detection-at-physiological-concentrations-for-analysis-of-islet-performance
#19
Hyunjun Cho, Shailabh Kumar, Daejong Yang, Sagar R Vaidyanathan, Kelly Woo, Ian Garcia, Hao Jan Shue, Youngzoon Yoon, Kevin Ferreri, Hyuck Choo
Label-free optical detection of insulin would allow in vitro assessment of pancreatic cell functions in their natural state and expedite diabetes-related clinical research and treatment, however no existing method has met these criteria at physiological concentrations. Using spatially-uniform 3D gold-nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of insulin in the secretions from human pancreatic islets under low and high glucose environments without the use of labels such as antibodies or aptamers...
January 11, 2018: ACS Sensors
https://www.readbyqxmd.com/read/29322513/periodontitis-and-cancer-mortality-register-based-cohort-study-of-68-273-adults-in-10-year-follow-up
#20
Pia Heikkilä, Anna But, Timo Sorsa, Jari Haukka
Periodontitis, a multifactorial infection-induced low-grade chronic inflammation, can influence the process of carcinogenesis. We studied with 10 years follow-up of 68 273 adults-based cohort the involvement of periodontitis as a risk factor for cancer mortality. Periodontal status was defined based on procedure codes of periodontal treatment. Rate ratios and absolute differences of overall and cancer mortality rates were assessed with respect to periodontal status using multiplicative and additive Poisson regression models, respectively...
January 11, 2018: International Journal of Cancer. Journal International du Cancer
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