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https://www.readbyqxmd.com/read/29320741/endocytosis-of-katp-channels-drives-glucose-stimulated-excitation-of-pancreatic-%C3%AE-cells
#1
Young-Eun Han, Jung Nyeo Chun, Min Jeong Kwon, Young-Sun Ji, Myong-Ho Jeong, Hye-Hyun Kim, Sun-Hyun Park, Jong Cheol Rah, Jong-Sun Kang, Suk-Ho Lee, Won-Kyung Ho
Insulin secretion from pancreatic β cells in response to high glucose (HG) critically depends on the inhibition of KATP channel activity in HG. It is generally believed that HG-induced effects are mediated by the increase in intracellular ATP, but here, we showed that, in INS-1 cells, endocytosis of KATP channel plays a major role. Upon HG stimulation, resting membrane potential depolarized by 30.6 mV (from -69.2 to -38.6 mV) and KATP conductance decreased by 91% (from 0.243 to 0.022 nS/pF), whereas intracellular ATP was increased by only 47%...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29240812/effects-of-vaspin-on-pancreatic-%C3%AE-cell-secretion-via-pi3k-akt-and-nf-%C3%AE%C2%BAb-signaling-pathways
#2
Shiwei Liu, Xin Li, Yaru Wu, Ruixue Duan, Jiaxin Zhang, Fang Du, Qi Zhang, Yuanbin Li, Naishi Li
Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a recently discovered adipokine that has been implicated in diabetes mellitus and other metabolic disorders. However, the effects of vaspin on pancreatic β cell function and related mechanisms are not fully understood. Thus, the present study was performed to investigate the effects of vaspin on pancreatic β cell function and the potential underlying mechanisms. Both in vitro (rat insulinoma cells, INS-1) and in vivo (high fat diet fed rats) experiments were conducted...
2017: PloS One
https://www.readbyqxmd.com/read/29229616/glutamine-elicited-secretion-of-glucagon-like-peptide-1-glp-1-is-governed-by-an-activated-glutamate-dehydrogenase
#3
Lotta E Andersson, Liliya Shcherbina, Mahmoud Al-Majdoub, Neelanjan Vishnu, Claudia Balderas Arroyo, Jonathan Aste Carrara, Claes B Wollheim, Malin Fex, Hindrik Mulder, Nils Wierup, Peter Spégel
Glucagon-like peptide-1 (GLP-1), secreted from intestinal L-cells, glucose-dependently stimulates insulin secretion from beta-cells. This glucose-dependence prevents hypoglycemia, rendering GLP-1 analogues a useful and safe treatment modality in type-2 diabetes. While the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear.We investigated how GLP-1 secretion is metabolically coupled in L-cells (GLUTag) and in vivo in mice, using the insulin-secreting cell-line INS-1 832/13 as reference...
December 11, 2017: Diabetes
https://www.readbyqxmd.com/read/29226686/enhanced-specific-activity-by-multi-chelation-of-exendin-3-leads-to-improved-image-quality-and-in-vivo-beta-cell-imaging
#4
Lieke Joosten, Maarten Brom, Hanneke Peeters, Sandra Heskamp, Martin Behe, Otto C Boerman, Martin Gotthardt
OBJECTIVE: Glucagon like peptide-1 receptor (GLP-1R) targeting using radiolabeled exendin is a promising approach to non-invasively visualize and determine beta cell mass (BCM), which could help to unravel the pathophysiology of diabetes. However, saturation of the GLP-1R on beta cells occurs at low peptide doses, since the number of receptors expressed under physiological conditions is low. Therefore, tracers with high specific activities are required to sensitively image small variations in BCM...
December 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29225191/the-comprehensive-electrophysiological-study-of-curcuminoids-on-delayed-rectifier-k-currents-in-insulin-secreting-cells
#5
Ping-Chung Kuo, Chia-Jung Yang, Yu-Chi Lee, Pei-Chun Chen, Yen-Chin Liu, Sheng-Nan Wu
Curcumin (CUR) has been demonstrated to induce insulin release from pancreatic β-cells; however, how curcuminoids (including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)) exert any possible effects on membrane ion currents inherently in insulin-secreting cells remains largely unclear. The effects of CUR and other structurally similar curcuminoids on ion currents in rat insulin-secreting (INS-1) insulinoma cells were therefore investigated in this study. The effects of these compounds on ionic currents and membrane potential were studied by patch-clamp technique...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225069/stimulation-of-b-raf-increases-c-jun-and-c-fos-expression-and-upregulates-ap-1-regulated-gene-transcription-in-insulinoma-cells
#6
Daniel S Langfermann, Oliver G Rössler, Gerald Thiel
Stimulation of pancreatic β-cells with glucose activates the protein kinases B-Raf and extracellular signal-regulated protein kinase that participate in glucose sensing. Inhibition of both kinases results in impairment of glucose-regulated gene transcription. To analyze the signaling pathway controlled by B-Raf, we expressed a conditionally active form of B-Raf in INS-1 insulinoma cells. Here, we show that stimulation of B-Raf strongly activated the transcription factor AP-1 which is accompanied by increased c-Jun and c-Fos promoter activities, an upregulation of c-Jun and c-Fos biosynthesis, and elevated transcriptional activation potentials of c-Jun and c-Fos...
December 7, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29207597/inhibition-of-miro1-disturbs-mitophagy-and-pancreatic-%C3%AE-cell-function-interfering-insulin-release-via-irs-akt-foxo1-in-diabetes
#7
Lingling Chen, Chunyan Liu, Jianfeng Gao, Zhiwen Xie, Lawrence W C Chan, Damien J Keating, Yibin Yang, Jiazhong Sun, Fuling Zhou, Yongchang Wei, Xiuli Men, Sijun Yang
Mitochondrial function is essential to meet metabolic demand of pancreatic beta cells respond to high nutrient stress. Mitophagy is an essential component to normal pancreatic β-cell function and has been associated with β-cell failure in Type 2 diabetes (T2D). Our previous studies have indicated that mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory responses and subsequent insulin resistance. However, the in vivo mechanism by which Miro1 underlies mitophagy has not been identified...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29192236/estrogen-attenuates-agtr1-expression-to-reduce-pancreatic-%C3%AE-cell-death-from-high-glucose
#8
Suwattanee Kooptiwut, Keerati Wanchai, Namoiy Semprasert, Chatchawan Srisawat, Pa-Thai Yenchitsomanus
Chronic exposure of pancreatic β-cells to high glucose levels results in β-cell dysfunction and death. These effects can be protected by estrogen. The local pancreatic renin-angiotensin system (RAS) has been shown as a novel pathological pathway of high-glucose-induced cell death. The effect of estrogen on pancreatic RAS is still unknown. This study examines whether estrogen protects against pancreatic β-cell death caused by glucotoxicity via a decrease in the pancreatic β-cell RAS pathway. When INS-1 cells were cultured in a high glucose medium, cell death was significantly higher than when the cells were cultured in a basal glucose medium; similarly, there were also higher levels of AGTR1 and p47 ph ° x mRNA, and protein expression...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29163176/jiang-tang-xiao-ke-granule-play-an-anti-diabetic-role-in-diabetic-mice-pancreatic-tissue-by-regulating-the-mrnas-and-micrornas-associated-with-pi3k-akt-signaling-pathway
#9
Fang-Fang Mo, Tian An, Zi-Jian Zhang, Yu-Fei Liu, Hai-Xia Liu, Yan-Yun Pan, Jia-Nan Miao, Dan-Dan Zhao, Xiu-Yan Yang, Dong-Wei Zhang, Guang-Jian Jiang, Si-Hua Gao
Purpose: To investigate the effect of JTXK granule on the expression pattern of miRNA in pancreatic tissue of KKAy diabetic mice, and to explore the molecular mechanism and pathways of JTXK granule in anti-diabetic effect. Methods: We used high fat diet (HFD) to induce the KKAy diabetic mice and screened the differentially expressed miRNAs (DEMs) between JTXK-treated group (n = 6) and the diabetic group (n = 6) using MicroRNA (miRNA) Microarray. C57BL/6J mice were given a normal diet as the control group (n = 6)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29157578/evaluation-of-the-insulinotropic-and-glucose-lowering-actions-of-zebrafish-gip-in-mammalian-systems-evidence-for-involvement-of-the-glp-1-receptor
#10
Galyna V Graham, J Michael Conlon, Yasser H Abdel-Wahab, Victor A Gault, Peter R Flatt
The insulinotropic properties of zebrafish GIP (zfGIP) were assessed in vitro using clonal pancreatic β-cell lines and isolated mouse islets and acute effects on glucose tolerance and insulin release in vivo were evaluated in mice. The peptide produced a dose-dependent increase in the rate of insulin release from BRIN-BD11 rat clonal β-cells at concentrations ≥30nM. Insulin release from 1.1 B4 human clonal β-cells and mouse islets was significantly increased by zfGIP (10nM and 1μM). The in vitro insulinotropic activity of zfGIP was decreased after incubating BRIN-BD11 cells with the GLP-1 receptor antagonist, exendin-4(9-39) (p<0...
November 17, 2017: Peptides
https://www.readbyqxmd.com/read/29145148/honokiol-protects-pancreatic-%C3%AE-cell-against-high-glucose-and-intermittent-hypoxia-induced-injury-by-activating-nrf2-are-pathway-in-vitro-and-in-vivo
#11
Chen-Guang Li, Chang-Lin Ni, Min Yang, Yun-Zhao Tang, Zhu Li, Yan-Juan Zhu, Zhen-Huan Jiang, Bei Sun, Chun-Jun Li
Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with glucose intolerance, insulin resistance and type 2 diabetes mellitus (T2DM). Although several studies have revealed that intermittent hypoxia (IH) in OSAHS may further aggravate pancreatic β cell damage and promote the evolution of type 2 diabetes (T2DM) by increasing oxidative stress, the underlying mechanisms are unclear. Honokiol, a potent radical scavenger, has been demonstrated to ameliorate oxidative stress in many cases. The present study aimed to explore the potential mechanism of IH and diabetes synergistically damage and destruct the pancreatic β cell, examine the effects of honokiol on ameliorating pancreatic β cell injury in this context and explore the mechanism of such effects...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29138225/androgen-signaling-expands-%C3%AE-cell-mass-in-male-rats-and-%C3%AE-cell-androgen-receptor-is-degraded-under-high-glucose-conditions
#12
Naoki Harada, Yasuhiro Yoda, Yusuke Yotsumoto, Tatsuya Masuda, Yuji Takahashi, Takahiro Katsuki, Kenji Kai, Nobuaki Shiraki, Hiroshi Inui, Ryoichi Yamaji
A deficient pancreatic β-cell mass increases the risk of type 2 diabetes mellitus. Here, we investigated the effects of testosterone on the development of pancreatic β-cell mass in male rats. The β-cell mass of male rats castrated at 6 weeks of age was reduced to ~30% of that of control rats at 16 weeks of age, and castration caused glucose intolerance. Loss of β-cell mass occurred due to decreases in islet density/pancreas and β-cell cluster size. Castration was negatively associated with the number of Ki67-positive β-cells and positively associated with the number of TUNEL-positive β-cells...
November 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29128354/angiotensin-converting-enzyme-2-regulates-mitochondrial-function-in-pancreatic-%C3%AE-cells
#13
Ting-Ting Shi, Fang-Yuan Yang, Chang Liu, Xi Cao, Jing Lu, Xue-Lian Zhang, Ming-Xia Yuan, Chen Chen, Jin-Kui Yang
Mitochondrial metabolism plays an essential role in the regulation of insulin release and glucose homeostasis. Evidence demonstrated that the angiotensin-converting enzyme 2 (ACE2) participates in the regulation of glucose metabolism, however, its role in mitochondrial metabolism remains unclear. The purpose of our study was to determine if ACE2 can regulate mitochondrial function in pancreatic β-cells. We found that ACE2 over-expression restored glucose-stimulated insulin secretion (GSIS) and mitochondrial membrane potential (MMP) in the presence of H2O2 in INS-1 cells...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29122960/mir-335-overexpression-impairs-insulin-secretion-through-defective-priming-of-insulin-vesicles
#14
Vishal A Salunkhe, Jones K Ofori, Nikhil R Gandasi, Sofia A Salö, Sofia Hansson, Markus E Andersson, Anna Wendt, Sebastian Barg, Jonathan L S Esguerra, Lena Eliasson
MicroRNAs contribute to the maintenance of optimal cellular functions by fine-tuning protein expression levels. In the pancreatic β-cells, imbalances in the exocytotic machinery components lead to impaired insulin secretion and type 2 diabetes (T2D). We hypothesize that dysregulated miRNA expression exacerbates β-cell dysfunction, and have earlier shown that islets from the diabetic GK-rat model have increased expression of miRNAs, including miR-335-5p (miR-335). Here, we aim to determine the specific role of miR-335 during development of T2D, and the influence of this miRNA on glucose-stimulated insulin secretion and Ca(2+)-dependent exocytosis...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29119245/development-and-characterisation-of-a-novel-glucagon-like-peptide-1-receptor-antibody
#15
Emma K Biggs, Lihuan Liang, Jacqueline Naylor, Shimona Madalli, Rachel Collier, Matthew P Coghlan, David J Baker, David C Hornigold, Peter Ravn, Frank Reimann, Fiona M Gribble
AIMS/HYPOTHESIS: Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo...
November 9, 2017: Diabetologia
https://www.readbyqxmd.com/read/29111283/pancreatic-islet-autonomous-effect-of-arsenic-on-insulin-secretion-through-endoplasmic-reticulum-stress-autophagy-pathway
#16
Wei Wu, Xiaofeng Yao, Liping Jiang, Qiaoting Zhang, Jie Bai, Tianming Qiu, Lei Yang, Ni Gao, Guang Yang, Xiaofang Liu, Min Chen, Xiance Sun
Inorganic arsenic is a worldwide environmental pollutant. Arsenic's relationship with the incidence of diabetes arouses concerns on its etiological mechanism. In this study, the glucose-stimulated insulin secretion (GSIS) from isolated pancreatic islets of As2O3-treated mice was significantly lower than that of control mice. It indicated that the effect of As2O3-inhibited GSIS was pancreatic islet-autonomous. The level of phospho-PERK (p-PERK), a biomarker of endoplasmic reticulum (ER) stress, in pancreas of As2O3-treated mice was increased significantly...
October 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29101219/mir-204-controls-glucagon-like-peptide-1-receptor-expression-and-agonist-function
#17
SeongHo Jo, Junqin Chen, Guanlan Xu, Truman B Grayson, Lance A Thielen, Anath Shalev
Glucagon-like peptide 1 receptor (GLP1R) agonists are widely used to treat diabetes. However, their function is dependent on adequate GLP1R expression, which is downregulated in diabetes. GLP1R is highly expressed on pancreatic beta cells and activation by endogenous incretin or GLP1R agonists increases cAMP generation, which stimulates glucose-induced beta cell insulin secretion and helps maintain glucose homeostasis. We now have discovered that the highly beta cell-enriched microRNA, miR-204, directly targets the 3'UTR of GLP1R and thereby downregulates its expression in the beta-cell-derived rat INS-1 cell line and primary mouse and human islets...
November 3, 2017: Diabetes
https://www.readbyqxmd.com/read/29057810/synthesis-characterization-and-biological-evaluations-of-1-3-5-triazine-derivatives-of-metformin-cyclization-with-berberine-and-magnolol-in-the-presence-of-sodium-methylate
#18
Han Cao, Shili Liao, Wenjing Zhong, Xuerong Xiao, Jiancheng Zhu, Weimin Li, Xia Wu, Yifan Feng
The novel target products were synthesized in the formation of a triazine ring from berberine, magnolol, and metformin catalyzed by sodium methylate. The structures of products 1-3 were firstly confirmed by extensive spectroscopic analyses and single-crystal X-ray diffraction. The crystal structures of the target product 2 and the intermediate product 7b were reported for the first time. All target products were evaluated for their anti-inflammatory and antidiabetic activities against INS-1 and RAW264.1 cells in vitro and all products showed excellent anti-inflammatory effects and anti-insulin resistance effects...
October 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29042678/carnosine-scavenging-of-glucolipotoxic-free-radicals-enhances-insulin-secretion-and-glucose-uptake
#19
Michael J Cripps, Katie Hanna, Charlie Lavilla, Sophie R Sayers, Paul W Caton, Craig Sims, Luigi De Girolamo, Craig Sale, Mark D Turner
The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038359/hyperoxia-reduces-insulin-release-and-induces-mitochondrial-dysfunction-with-possible-implications-for-hyperoxic-treatment-of-neonates
#20
Ingrid Hals, Tsuyoshi Ohki, Rinku Singh, Zuheng Ma, Anneli Björklund, Chandima Balasuriya, Hanne Scholz, Valdemar Grill
We previously showed that hyperoxia in vitro negatively affects beta cells of the rat. Here, we tested for possible clinical significance as well as mitochondrial interactions by hyperoxia, using human islets (function and viability), INS-1 832/13 cells (mitochondrial metabolism), and mouse neonates (effects in vivo). Lastly, we assessed relevant parameters in a cohort of individuals born preterm and then exposed to hyperoxia. Human islets and INS-1 832/13 cells were exposed to 24 h of hyperoxia (90-92% oxygen)...
October 2017: Physiological Reports
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