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https://www.readbyqxmd.com/read/28212395/delayed-apoptosis-allows-islet-%C3%AE-cells-to-implement-an-autophagic-mechanism-to-promote-cell-survival
#1
Heather L Hayes, Brett S Peterson, Jonathan M Haldeman, Christopher B Newgard, Hans E Hohmeier, Samuel B Stephens
Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets...
2017: PloS One
https://www.readbyqxmd.com/read/28198575/tat-biliverdin-reductase-a-protects-ins-1-cells-from-human-islet-amyloid-polypeptide-induced-cytotoxicity-by-alleviating-oxidative-stress-and-er-stress
#2
Su Jin Lee, Hyung Kyung Kang, Won Sik Eum, Jinseu Park, Soo Young Choi, Hyeok Yil Kwon
Human islet amyloid polypeptide (hIAPP), a major constituent of islet amyloid deposits, induces pancreatic β-cell apoptosis and eventually contributes to β-cell deficit in patients with type 2 diabetes mellitus (T2DM). In this study, Tat-mediated transduction of biliverdin reductase A (BLVRA) was investigated in INS-1 cells to examine whether exogenous supplementation of BLVRA prevented hIAPP-induced apoptosis and dysfunction in insulin secretion in β-cells. Tat-BLVRA fusion protein was efficiently delivered into INS-1 cells in a time- and dose-dependent manner...
February 15, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28173719/exo-mir-15a-transfer-from-the-pancreas-augments-diabetic-complications-by-inducing-oxidative-stress
#3
Tengku Ain Kamalden, Anne M Macgregor-Das, Sangeetha M Kannan, Brittany Dunkerly-Eyring, Nurliza Khaliddin, Zhenhua Xu, Anthony P Fusco, Syatirah Abu Yazib, Rhuen Chiou Chow, Elia J Duh, Marc K Halushka, Charles Steenbergen, Samarjit DAS
AIMS: Mi(cro)RNAs, one type of non-coding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type-2-diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D. RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic-β-cells...
February 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28160851/7-8-dihydroxycoumarin-daphnetin-protects-ins-1-pancreatic-%C3%AE-cells-against-streptozotocin-induced-apoptosis
#4
Ramachandran Vinayagam, Baojun Xu
BACKGROUND AND OBJECTIVE: Daphnetin (7, 8-dihydroxycoumarin), a natural coumarin compound, is known to exhibit antioxidant and anti-inflammatrory effects. However, the underlying mechanisms of its anti-apoptotic and antidiabetic effects yet not been examined. Therefore, the present work studied the anti-apoptotic and anti-diabetic effects of daphnetin by in vitro experiments. METHODS: The rat insulinoma (INS-1) cells were pre-treated with daphnetin at different concentrations (1, 10, 20 and 40µM) for 24h followed by exposition to streptozotocin (STZ) (3mM) for 12h...
January 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28157263/a-phosphoinositide-specific-phospholipase-c-pathway-elicits-stress-induced-ca-2-signals-and-confers-salt-tolerance-to-rice
#5
Li Li, Fawei Wang, Peiwen Yan, Wen Jing, Chunxia Zhang, Jörg Kudla, Wenhua Zhang
In animal cells, phospholipase C (PLC) isoforms predominantly hydrolyze phosphatidylinositol-4,5-biphosphates [PtdIns(4,5)P2 ] into the second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3 ] to regulate diverse biological processes. By contrast, the molecular mechanisms and physiological significance of PLC signaling in plants still awaits full elucidation. Here, we identified a rice (Oryza sativa cv) PI-PLC, OsPLC1, which preferred to hydrolyze phosphatidylinositol-4-phosphate (PtdIns4P) and elicited stress-induced Ca(2+) signals regulating salt tolerance...
February 3, 2017: New Phytologist
https://www.readbyqxmd.com/read/28115068/the-role-of-oxidative-stress-in-dna-damage-in-pancreatic-%C3%AE-cells-induced-by-di-2-ethylhexyl-phthalate
#6
Yan She, Liping Jiang, Liangliang Zheng, Heming Zuo, Min Chen, Xiance Sun, Qiujuan Li, Chengyan Geng, Guang Yang, Lijie Jiang, Xiaofang Liu
Di(2-ethyhexyl) phthalate (DEHP) is commonly used as a plasticizer, which loosely binds to plastic materials and easily leaches out of these products and enters into the environment. Exposure to DEHP can impair pancreatic beta cells (INS-1 cells)function, which is associated with Insulin Resistance (IR) and type 2 diabetes. However, the mechanism of how DEHP leads to Insulin Resistance is unknown. Our results showed that the cell viability of INS-1 cells exposed to DEHP (0-1600 μM) were decreased in a concentration-dependent manner...
January 20, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28108607/insulin-like-growth-factor-binding-protein-1-could-improve-glucose-regulation-and-insulin-sensitivity-through-its-rgd-domain
#7
Natalie J Haywood, Paul A Cordell, Kar Yeun Tang, Natallia Makova, Nadira Y Yuldasheva, Helen Imrie, Hema Viswambharan, Alexander F Bruns, Richard M Cubbon, Mark T Kearney, Stephen B Wheatcroft
Low circulating levels of insulin-like growth factor binding protein 1 (IGFBP-1) are associated with insulin resistance and predict the development of type 2 diabetes. IGFBP-1 can affect cellular functions independently of IGF binding through an Arg-Gly-Asp (RGD) integrin-binding motif. Whether causal mechanisms underlie the favorable association of high IGFBP-1 levels with insulin sensitivity and whether these could be exploited therapeutically remain unexplored. We used recombinant IGFBP-1 and a synthetic RGD-containing hexapeptide in complementary in vitro signaling assays and in vivo metabolic profiling in obese mice to investigate the effects of IGFBP-1 and its RGD domain on insulin sensitivity, insulin secretion, and whole-body glucose regulation...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28101851/importance-of-radioactive-labelling-to-elucidate-inositol-polyphosphate-signalling
#8
REVIEW
Miranda S C Wilson, Adolfo Saiardi
Inositol polyphosphates, in their water-soluble or lipid-bound forms, represent a large and multifaceted family of signalling molecules. Some inositol polyphosphates are well recognised as defining important signal transduction pathways, as in the case of the calcium release factor Ins(1,4,5)P3, generated by receptor activation-induced hydrolysis of the lipid PtdIns(4,5)P2 by phospholipase C. The birth of inositol polyphosphate research would not have occurred without the use of radioactive phosphate tracers that enabled the discovery of the "PI response"...
February 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28098903/vitexin-alleviates-lipopolysaccharide%C3%A2-induced-islet-cell-injury-by-inhibiting-hmgb1-release
#9
Feifei Wang, Jiajing Yin, Yujin Ma, Hongwei Jiang, Yanbo Li
Diabetes mellitus (DM) is a chronic metabolic disease, where the predominant pathogenesis is pancreatic β‑cells dysfunction or injury. It has been well established that inflammation leads to a gradual exhaustion of pancreatic β‑cell function with decreased β‑cell mass likely resulting from pancreatic β‑cells apoptosis or death. Vitexin, a major bioactive flavonoid compound in plants has numerous pharmacological properties, including antioxidant, anti‑inflammatory and antimyeloperoxidase. Whether vitexin can protect pancreatic β‑cells against lipopolysaccharide (LPS)‑induced pro‑inflammatory cytokine production and apoptosis has received little attention...
January 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28089587/development-of-111-in-labeled-exendin-9-39-derivatives-for-single-photon-emission-computed-tomography-imaging-of-insulinoma
#10
Hiroyuki Kimura, Hirokazu Matsuda, Yu Ogawa, Hiroyuki Fujimoto, Kentaro Toyoda, Naotaka Fujita, Kenji Arimitsu, Keita Hamamatsu, Yusuke Yagi, Masahiro Ono, Nobuya Inagaki, Hideo Saji
Insulinoma is a tumor derived from pancreatic β-cells, and the resulting hyperinsulinemia leads to characteristic hypoglycemia. Recent studies have reported the frequent overexpression of glucagon-like peptide-1 receptor (GLP-1R) in human insulinomas, suggesting that the binding of a radiolabeled compound to GLP-1R is useful for the imaging of such tumors. Exendin(9-39), a fragment peptide of exendin-3 and -4, binds GLP-1R with high affinity and acts as an antagonist. Accordingly, radiolabeled exendin(9-39) derivatives have also been investigated as insulinoma imaging probes that might be less likely to induce hypoglycemia...
January 3, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28069865/interleukin-22-restored-mitochondrial-damage-and-impaired-glucose-stimulated-insulin-secretion-through-down-regulation-of-uncoupling-protein-2-in-ins-1-cells
#11
Minling Hu, Hanxiao Lin, Li Yang, Yanzhen Cheng, Hua Zhang
Defective glucose-stimulated insulin secretion (GSIS) induced by chronic exposure to fatty acids is a hallmark of type 2 diabetes (T2D). Interleukin-22 (IL-22) has been shown to exert beneficial effects on insulin secretion and to protect pancreatic β-cells from stress. Moreover, uncoupling protein-2 (UCP-2) plays a central role in the regulation of GSIS and β-cell dysfunction, whereas the role of UCP-2 in IL-22-enhanced glycemic control under conditions of lipotoxicity remains unclear. In this present study, we investigated the effects of IL-22 on rat insulin-secreting cells (INS-1 cells) and the mechanisms that underlie IL-22 and lipotoxicity-impaired GSIS in vitro...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28027979/the-impairment-of-glucose-stimulated-insulin-secretion-in-pancreatic-%C3%AE-cells-caused-by-prolonged-glucotoxicity-and-lipotoxicity-is-associated-with-elevated-adaptive-antioxidant-response
#12
Jingqi Fu, Qi Cui, Bei Yang, Yongyong Hou, Huihui Wang, Yuanyuan Xu, Difei Wang, Qiang Zhang, Jingbo Pi
Type 2 diabetes (T2D) is a progressive disease characterized by sustained hyperglycemia and is frequently accompanied by hyperlipidemia. Deterioration of β-cell function in T2D patients may be caused, in part, by long-term exposure to high concentrations of glucose and/or lipids. We developed systems to study how chronic glucotoxicity and lipotoxicity might be linked to the impairment of glucose-stimulated insulin secretion (GSIS) machinery in pancreatic β-cells. INS-1 (832/13) were exposed to glucose and/or palmitate for up to 10 weeks...
February 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28008587/neutral-ceramidase-secreted-via-exosome-protects-against-palmitate-induced-apoptosis-in-ins-1-cells
#13
S Tang, F Luo, Y M Feng, X Wei, H Miao, Y B Lu, Y Tang, D F Ding, J F Jin, Q Zhu
Aims: To investigate the effects of neutral ceramidase (NCDase) packaged in exosomes that are secreted from β-cells on free fatty acid (FFA)-induced β-cells apoptosis and its role in regulation of sphingolipid-mediated signaling pathway. Methods: HPLC and Western blotting were performed to determine NCDase activity and expression. Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis. Electrospray ionization tandem mass spectrometry was used for ceramide (Cer), sphingosine-1-phosphate (S1P), and sphingosine (SPH) determination...
December 22, 2016: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28000177/geniposide-accelerates-proteasome-degradation-of-txnip-to-inhibit-insulin-secretion-in-pancreatic-%C3%AE-cells
#14
C Y Liu, Y N Hao, F Yin, Y L Zhang, J H Liu
PURPOSE: To analyze the role of geniposide in the protein degradation of Txnip and to determine the impact of Txnip on geniposide-regulated GSIS in pancreatic INS-1 cells. METHODS: The content of Txnip protein was measured by western blot; insulin content and glucose uptake were determined by ELISA; and knockdown of Txnip was the method of RNA interference. RESULTS: Glucose induces a rapid increase in Txnip protein, and geniposide accelerates the degradation of Txnip via proteasome pathway in the presence of high glucose (25 mM) in INS-1 pancreatic β-cells...
December 20, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27989255/a-randomised-controlled-trial-of-repeated-filmed-social-contact-on-reducing-mental-illness-related-stigma-in-young-adults
#15
S Koike, S Yamaguchi, Y Ojio, K Ohta, T Shimada, K Watanabe, G Thornicroft, S Ando
AIMS: Public stigma alters attitudes towards people with mental illness, and is a particular concern for young people since most mental health problems occur in adolescence and young adulthood. However, little is known about the long-term effects of repeated filmed social contact (FSC) on reducing mental health-related stigma among young adults in the general population, compared with self-instructional Internet search (INS) and control interventions. METHODS: This study is a parallel-group randomised controlled trial over 12 months conducted in Tokyo, Japan...
December 19, 2016: Epidemiology and Psychiatric Sciences
https://www.readbyqxmd.com/read/27956176/glucagon-like-peptide-1-effects-lipotoxic-oxidative-stress-by-regulating-the-expression-of-micrornas
#16
Zhiying Zhang, Huifang Liu, Qiang Li
Aim to confirm whether the treatment of GLP-1 can modulated body weight, lipid metabolism, insulin content, pancreas oxidative stress, improved T-AOC, MDA levels related to FFA-Induced oxidative stress in C57BL/6 mice and INS-1 cells. In this study, GLP-1 makes the expression of AMPK, PPARα, CPT1A and SIRT1 increased, and the expression of SREBP1c, miR-33 and miR-370 decreased. Interestingly, the effects of GLP-1 were less dose dependent as GLP-1 regulated the FFA, which related to gene expression at much lower doses (3 μg/kg, 10 mM, mice and INS-1 respectively) and effects were relatively maintained at higher dose (30 μg/kg, 100 mM, mice and INS-1 respectively) as well...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27939242/ex4-stabilizes-and-activates-nrf2-via-pkc%C3%AE-contributing-to-the-prevention-of-oxidative-stress-induced-pancreatic-beta-cell-damage
#17
Mi-Hwi Kim, Eung-Hwi Kim, Hye Seung Jung, Dongki Yang, Eun-Young Park, Hee-Sook Jun
Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H2O2. Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured...
December 7, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27914526/jiawei-erzhiwan-improves-menopausal-metabolic-syndrome-by-enhancing-insulin-secretion-in-pancreatic-%C3%AE-cells
#18
Xiao-Meng Wan, Mu Zhang, Pei Zhang, Zhi-Shen Xie, Feng-Guo Xu, Ping Zhou, Shi-Ping Ma, Xiao-Jun Xu
Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE)...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27912197/rac1-nadph-oxidase-signaling-promotes-cd36-activation-under-glucotoxic-conditions-in-pancreatic-beta-cells
#19
Suma Elumalai, Udayakumar Karunakaran, In Kyu Lee, Jun Sung Moon, Kyu Chang Won
We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus...
November 23, 2016: Redox Biology
https://www.readbyqxmd.com/read/27900263/islet-chrebp-%C3%AE-is-increased-in-diabetes-and-controls-chrebp-%C3%AE-and-glucose-induced-gene-expression-via-a-negative-feedback-loop
#20
Gu Jing, Junqin Chen, Guanlan Xu, Anath Shalev
OBJECTIVE: Carbohydrate-response element-binding protein (ChREBP) is the major transcription factor conferring glucose-induced gene expression in pancreatic islets, liver and adipose tissue. Recently, a novel ChREBP isoform, ChREBP-β, was identified in adipose tissue and found to be also expressed in islets and involved in glucose-induced beta cell proliferation. However, the physiological function of this less abundant β-isoform in the islet, and in diabetes, is largely unknown. The aims of the present study, therefore, were to determine how diabetes affects ChREBP-β and elucidate its physiological role in pancreatic beta cells...
December 2016: Molecular Metabolism
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