1.Signaling mechanisms of glucose-induced F-actin remodeling in pancreatic islet beta cells.
Michael A KALWAT ; Debbie C THURMOND
Experimental & Molecular Medicine 2013;45(8):e37-
The maintenance of whole-body glucose homeostasis is critical for survival, and is controlled by the coordination of multiple organs and endocrine systems. Pancreatic islet beta cells secrete insulin in response to nutrient stimuli, and insulin then travels through the circulation promoting glucose uptake into insulin-responsive tissues such as liver, skeletal muscle and adipose. Many of the genes identified in human genome-wide association studies of diabetic individuals are directly associated with beta cell survival and function, giving credence to the idea that beta-cell dysfunction is central to the development of type 2 diabetes. As such, investigations into the mechanisms by which beta cells sense glucose and secrete insulin in a regulated manner are a major focus of current diabetes research. In particular, recent discoveries of the detailed role and requirements for reorganization/remodeling of filamentous actin (F-actin) in the regulation of insulin release from the beta cell have appeared at the forefront of islet function research, having lapsed in prior years due to technical limitations. Recent advances in live-cell imaging and specialized reagents have revealed localized F-actin remodeling to be a requisite for the normal biphasic pattern of nutrient-stimulated insulin secretion. This review will provide an historical look at the emergent focus on the role of the actin cytoskeleton and its regulation of insulin secretion, leading up to the cutting-edge research in progress in the field today.
Actins/*metabolism
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Animals
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Exocytosis/drug effects
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Glucose/*pharmacology
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Humans
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Insulin/metabolism
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Insulin-Secreting Cells/drug effects/enzymology/*metabolism
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Signal Transduction/*drug effects
2.Research progress on hypoglycemic effect and its mechanism of action of medicinal fungal polysaccharides.
Rong DAI ; Ru-ming LIU ; Jian-hui XIAO
China Journal of Chinese Materia Medica 2015;40(2):174-179
Due to substantial morbidity and high complications, diabetes mellitus is considered as the third "killer" in the world. Medicinal fungal polysaccharides, as water-soluble macromolecular substances with low toxicity, exhibit diversified pharmacological actions such as immune regulation, anti-tumor, antivirus, antioxidant, anti-aging, hypoglycemic effect and improving liver and kidney function. In recent year, a number of investigators reported medicinal fungal polysaccharides showed good anti-diabetes and hypoglycemic activity, and their acting mechanisms involved in glycometabolism and β cell function, e. g. promoting glycogen synthesis, promoting glycolysis, inhibiting the activity of α-glucosidase, promoting insulin secretion, increasing insulin sensitivity, enhancing antioxidation. Therefore, the hypoglycemic activity and its mechanisms of action of medicinal fungal polysaccharides showed characteristics of multiple effects, multi-target, and multi-pathway regulation. These finding suggest that medicinal fungal polysaccharides are a promising source for the development of discovery of anti-diabetic agent.
Animals
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Carbohydrate Metabolism
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drug effects
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Fungal Polysaccharides
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pharmacology
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Humans
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Hypoglycemic Agents
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pharmacology
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Insulin Resistance
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Insulin-Secreting Cells
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drug effects
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Oxidative Stress
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drug effects
3.Mechanism of the apoptosis of rat pancreas islet β cell strain (INS-1 cells) induced by sodium arsenite.
Xiao PAN ; Li-ping JIANG ; Lai-fu ZHONG ; Cheng-yan GENG ; Xian-ce SUN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2012;30(7):481-484
OBJECTIVETo study mechanism of the apoptosis of rat pancreas islet β cell strain (INS-1 cells) induced by sodium arsenite.
METHODSINS-1 cells were exposed to sodium arsenite at the different concentrations. MTT assay was used to detect the viability of INS-1 cells. The potentials on mitochondrial membrane and lysosome membrane of INS-1 cells were determined with the fluorescence spectrophotometer. The apoptotic levels of INS-1 cells exposed to sodium arsenite were observed by a fluorescence microscope and flow cytometry.
RESULTSAfter exposure to sodium arsenite, the viability of INS-1 cells significantly decreased with the doses of sodium arsenite. At 24 h after exposure, the OD values of the mitochondrial membrane potentials declined observably with the doses of sodium arsenite (P < 0.01). At 48 h after exposure, the OD values of the lysosome membrane potentials significantly increased with the doses of sodium arsenite (P < 0.01). At 72 h after exposure, the apoptotic cells were observed under a fluorescence microscope and enhanced with the doses of sodium arsenite. The apoptosis cells with light blue, karyopyknosis, karyorrhexis, apoptotic body and chromatin concentration appeared. The results detected with flow cytometry indicated that after exposure, the apoptotic INS-1E cells significantly increased with the doses of sodium arsenite.
CONCLUSIONSThe sodium arsenite can induce the apoptosis of INS-1 cells through the mitochondria-lysosome pathway.
Animals ; Apoptosis ; drug effects ; Arsenites ; toxicity ; Cells, Cultured ; Insulin-Secreting Cells ; drug effects ; Lysosomes ; metabolism ; Membrane Potentials ; drug effects ; Mitochondria ; metabolism ; Rats ; Sodium Compounds ; toxicity
4.Divergent effects of lycopene on pancreatic alpha and beta cells.
Wei-Huang LIU ; Qiao-Na WANG ; Ying ZHOU ; Yan-Jun WANG ; Zan TONG
Acta Physiologica Sinica 2020;72(2):133-138
Lycopene is an antioxidant which has potential anti-diabetic activity, but the cellular mechanisms have not been clarified. In this study, different concentrations of lycopene were used to treat pancreatic alpha and beta cell lines, and the changes of cell growth, cell apoptosis, cell cycle, reactive oxygen species (ROS), ATP levels and expression of related cytokines were determined. The results exhibited that lycopene did not affect cell growth, cell apoptosis, cell cycle, ROS and ATP levels of alpha cells, while it promoted the growth of beta cells, increased the ratio of S phase, reduced the ROS levels and increased the ATP levels of beta cells. At the same time, lycopene treatment elevated the mRNA expression levels of tnfα, tgfβ and hif1α in beta cells. These findings suggest that lycopene plays cell-specific role and activates pancreatic beta cells, supporting its application in diabetes therapy.
Adenosine Triphosphate
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metabolism
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Apoptosis
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Carotenoids
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pharmacology
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Cell Cycle
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Cells, Cultured
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Cytokines
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metabolism
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Glucagon-Secreting Cells
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drug effects
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Humans
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Insulin-Secreting Cells
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drug effects
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Lycopene
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pharmacology
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Reactive Oxygen Species
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metabolism
5.Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells.
Xiao-Meng WAN ; Mu ZHANG ; Pei ZHANG ; Zhi-Shen XIE ; Feng-Guo XU ; Ping ZHOU ; Shi-Ping MA ; Xiao-Jun XU
Chinese Journal of Natural Medicines (English Ed.) 2016;14(11):823-834
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). The present study was designed to determine the anti-MMS effects of JE using ovariectomized (OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet β cells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion (GSIS), which was abolished by estrogen receptor (ER) antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.
Animals
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Drugs, Chinese Herbal
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administration & dosage
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Female
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Glucose
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metabolism
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Humans
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Insulin
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metabolism
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Insulin Secretion
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Insulin-Secreting Cells
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drug effects
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metabolism
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Menopause
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drug effects
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metabolism
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Metabolic Syndrome
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drug therapy
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metabolism
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Mice
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Rats
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Rats, Sprague-Dawley
6.Construction and identification of siRNA recombinant expression vector targeting parathyroid hormone 1 receptor gene and its effect on the cell cycle of INS-1 cells.
Hua-sheng LIANG ; Yao-ming XUE ; Yu-hua ZHONG
Journal of Southern Medical University 2010;30(9):2093-2096
OBJECTIVETo construct the expression vector of siRNA targeting parathyroid hormone 1 receptor (PTH1R) gene and evaluate its effect on the cell cycle of INS-1 cells.
METHODSThe sequences of PTH1R gene was retrieved from Genbank, and 4 pairs of oligonucleotides were synthesized and inserted into pSUPERretro RNAi, which was identified by RT-PCR and sequence analysis. The vectors were then transfected into INS-1 cells, in which the expression of PTH1R was observed by Western blotting to evaluate the transfection efficiency. The cell cycle of INS-1 cells in high glucose medium was detected by flow cytometry.
RESULTSRT-PCR and sequence analysis confirmed the correct construction of the siRNA recombinant expression vector targeting PTH1R gene. The vectors were successfully transfected into INS-1 cells, and the most effective vector was selected by Western blotting. Transfection with the siRNA for PTH1R gene silencing resulted in the inhibition of INS-1 form entering the S phase.
CONCLUSIONThe successful construction of the recombinant PTH1R-siRNA vectors establishes a basis for further study of protective role of the PTH1R gene in INS-1 cells in high glucose medium.
Cell Cycle ; drug effects ; Genetic Vectors ; genetics ; Glucose ; pharmacology ; Humans ; Insulin-Secreting Cells ; cytology ; drug effects ; metabolism ; RNA, Small Interfering ; genetics ; Receptor, Parathyroid Hormone, Type 1 ; genetics ; metabolism
7.Relationship between autophagy and T2DM and intervention effect of traditional Chinese medicine.
Jin-ni HONG ; Wei-wei LI ; Xue-mei WANG
China Journal of Chinese Materia Medica 2015;40(22):4351-4354
Insulin resistance and insulin secretion deficiency are main machanisms in inducing type 2 diabetes mellitus (T2DM), and mitochondria damage plays an important role in them. Research shows that autophagy is a self-protective mechanism of cells, which plays an important role in maintaining the normal structure and function of pancreatic β cells and improving insulin resistance. Previous studies show that traditional Chinese medicine can regulate cell autophagy to influence β cells and insulin resistance, type 2 diabetes mellitus and its complications. Thus this review will talk about the process of the relationship between autophagy and T2DM and the intervention effect of traditional Chinese medicine.
Animals
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Autophagy
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drug effects
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Diabetes Mellitus, Type 2
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drug therapy
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metabolism
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physiopathology
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Drugs, Chinese Herbal
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therapeutic use
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Humans
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Insulin
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metabolism
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Insulin Resistance
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Insulin-Secreting Cells
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cytology
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drug effects
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metabolism
8.Glitazones protects beta cell function from cytotoxic cytokines through PPAR gamma-dependent mechanisms.
Xia LI ; An-ping WANG ; Xiang YAN ; Gan HUANG ; Bi-lian LIU ; Zhi-guang ZHOU
Journal of Southern Medical University 2010;30(7):1530-1533
OBJECTIVETo investigate the protective effects of glitazones on islet beta cells and PPAR gamma dependence of such effects.
METHODSIL-1beta and IFN-gamma were used to treat NIT-1 cells, a beta cell line, to induce beta cell damage. The cells were pretreated with rosiglitazone and pioglitazone at different concentrations to study the protective effects of these drugs. The cell apoptosis rate was determined with Annexin V-FITC by flow cytometry, and the insulin secretion capacity of the cells was assessed with ELISA. GW9662 and PPARgamma-SiRNA were used to specifically inhibit PPAR to investigate the PPAR gamma-dependent mechanisms.
RESULTSRosiglitazone and pioglitazone at 10 micromol/L could significantly decrease the apoptosis of beta cells induced by the cytokines (apoptotic rates of 13.99% and 16.67% vs 51.33%, P<0.01). Rosiglitazone at 10 micromol/L and pioglitazone at 20 micromol/L were less effective than 10 micromol/L rosiglitazone and pioglitazone. The insulin secretion of the cytokine-treated cells decreased from 8.5-/+0.6 ng/ml of the control group to 3.6-/+0.5 ng/ml, while rosiglitazone and pioglitazone could increase the insulin secretion to 6.8-/+0.7 ng/ml and 5.9-/+0.9 ng/ml, respectively. When PPAR gamma was specifically inhibited by GW9662 and PPARgamma-SiRNA, the protective effects of rosiglitazone and pioglitazone were almost undetectable, and the apoptotic rate increased and insulin secretion decreased to the level of the cytokine-treated cells.
CONCLUSIONGlitazones can protect beta cells from apoptosis and impairment of insulin secretion function resulting from the cytotoxic cytokines via a PPAR gamma-dependent mechanism.
Animals ; Apoptosis ; drug effects ; Cell Line ; Insulin ; secretion ; Insulin-Secreting Cells ; drug effects ; metabolism ; secretion ; Interferon-gamma ; adverse effects ; Interleukin-1beta ; adverse effects ; Islets of Langerhans ; metabolism ; Mice ; Mice, Transgenic ; PPAR gamma ; metabolism ; Thiazolidinediones ; pharmacology
9.Study on differentiation of mesenchymal stem cells derived from human umbilical cord blood into insulin secreting cells.
Zuo-Hua CHI ; Yan LU ; Yuan ZHANG
Chinese Journal of Hematology 2008;29(10):679-683
OBJECTIVETo investigate the differential potential of mesenchymal stem cells (MSCs) derived from human umbilical cord blood (hUCB) into insulin-secreting cells and its inducing condition.
METHODSUCB nucleated cells (NCs) were isolated and cultured in Mesencult media. The obtained UCB MSC were purified by adherence method and expanded. Then they were induced with epidermal growth factor (EGF), B-mercaptoethanol and high concentration of glucose. The induced cells were identified by RT-PCR. Intracellular insulin was examined by immunocytochemistry. The quantity of insulin secretion and glucose-simulated insulin release were examined by chemiluminescence immunoassay. The induced cells were also transplanted into renal subcapsular space of STZ-induced hyperglycemic mice to observe the in vivo lowering effect on hyperglycemia.
RESULTSThe induced cells morphologically became round and were gathering into a mass. The expression of some genes related to pancreatic islet was found by RT-PCR. Chemiluminescence immunoassay showed insulin positivity and the cells secreted a low concentration of insulin [(0.37 +/- 0.06) mU/L]. The induced cells responded to high glucose challenge with a stimulation index of 1.76. After those cells grafted into renal sub-capsule there was an in vivo lowering effect on blood glucose level on STZ hyperglycemic mice.
CONCLUSIONMSCs from UCB can differentiated into insulin secreting cells.
Animals ; Cell Differentiation ; drug effects ; Cells, Cultured ; Diabetes Mellitus, Experimental ; surgery ; Fetal Blood ; cytology ; Humans ; Insulin ; metabolism ; Insulin-Secreting Cells ; cytology ; metabolism ; transplantation ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Mice ; Mice, Nude
10.Observation of insulin exocytosis by a pancreatic β cell line with total internal reflection fluorescence microscopy.
Zhao-ying FU ; Ya-ping WANG ; Yu CHEN
Chinese Medical Sciences Journal 2011;26(1):60-63
Animals
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Exocytosis
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drug effects
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physiology
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Glucose
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pharmacology
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Insulin
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secretion
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Insulin-Secreting Cells
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cytology
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drug effects
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metabolism
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Mice
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Microscopy, Fluorescence
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methods
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Potassium
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pharmacology
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Recombinant Fusion Proteins
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genetics
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metabolism
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Vesicle-Associated Membrane Protein 2
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genetics
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metabolism