U.S. flagAn official website of the United States government
                    Here's how you know **Official websites use .gov**
                            
                            A **.gov** website belongs to an official government organization in the United States.
 **Secure .gov websites use HTTPS**
                            
                            A **lock** (                            
                              A locked padlock                                                      
                            
                            ) or **https://** means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.


Menu Agricultural Research Service
						
                    U.S. DEPARTMENT OF AGRICULTURE
 Obesity and Metabolism Research: Davis, CA
 close



    Research

                    Research Projects
                                    Publications
                                    Collaborations
                                    News
                People

                    Staff Listing
                                    Careers


        


                    Laboratories
                        Bennett Group
                                    Huang Group
                                    Keim Group
                                    Laugero Group
                                    Newman GroupSearch small
                    Search
            
            ARS Home
                                About ARS
                                Contact Us




ARS Home Pacific West Area Davis, California Western Human Nutrition Research Center Obesity and Metabolism Research Research Publications at this Location





- ARS National Programs
- Search for a scientific manuscript
- Search for a research project
- ARS Software
- Programs and Projects
- Collaborations
- Subjects of Investigation
- Publications

Title:   Author  item
                                            Huang, Lipingitem
                                            MI, YUE - University Of Californiaitem
                                            Kirschke, Catherine
  Submitted to: Experimental Cell Research
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/22/2010
                                    Publication  Date: 7/1/2010
                                    Citation: Huang, L., Mi, Y., Kirschke, C.P. 2010. Over-expression of ZnT7 increases insulin synthesis and secretion in pancreatic beta-cells by promoting insulin gene transcription. Experimental Cell Research. 2010 Volume 316, Issue 16 2630-2643Interpretive Summary: The pancreas is a gland organ containing an endocrine gland producing hormones, such as insulin from beta-cells, glucagon from alpha-cells, and somatostatin from delta-cells, and an exocrine gland producing pancreatic digestive enzymes helping breakdown of the carbohydrates, protein, and fat in the small intestine. Impaired insulin synthesis and insulin secretion and perturbed proinsulin processing are hallmarks of beta-cell dysfunction in diabetes. Connections between zinc homeostasis and diabetes remain largely unknown. The zinc content in the pancreatic beta-cells is known to be among the highest in the body. Regulation of cellular zinc homeostasis in pancreatic beta-cells is still unknown. ZnT7 resides in the Golgi apparatus and plays a role in delivery of zinc into it. In this study, we demonstrated that zinc transporter 7 (ZnT7, Slc30a7) was co-expressed with insulin in the islet of Langerhans in the mouse pancreas. In RIN5mF cells (rat insulinoma cells), ZnT7 was found mainly residing in the perinuclear region of the cell, which is consistent with its Golgi apparatus localization. Over-expression of ZnT7 in RIN5mF cells increased total cellular insulin content leading to a high basal insulin secretion. Furthermore, glucose-induced insulin secretion was not altered in RIN5mF cells over-expressing ZnT7. Quantitative RT-PCR and 35S metabolic labeling analysis demonstrated that over-expression of ZnT7 in RIN5mF cells led to an increase of insulin mRNA expression and subsequent insulin protein synthesis in the cell. Metal-responsive elements (MREs) were identified in the promoter regions of the Ins1 and Ins2 genes. Mtf1, a metal-responsive transcription factor, was shown to specifically bind to the MRE in the Ins genes and activated the insulin gene transcription. Together, the data strongly suggest that ZnT7 plays an important role in regulating insulin expression by modulating Mtf1 transcriptional activity.
                                Technical Abstract: The mechanism by which zinc regulates insulin synthesis and secretion in pancreatic beta-cells is still unclear. Cellular zinc homeostasis is largely maintained by zinc transporters and intracellular zinc binding proteins. In this study, we demonstrated that zinc transporter 7 (ZnT7, Slc30a7) was co-expressed with insulin in the islet of Langerhans in the mouse pancreas. In RIN5mF cells (rat insulinoma cells), ZnT7 was found mainly residing in the perinuclear region of the cell, which is consistent with its Golgi apparatus localization. Over-expression of ZnT7 in RIN5mF cells increased total cellular insulin content leading to a high basal insulin secretion. Furthermore, glucose-induced insulin secretion was not altered in RIN5mF cells over-expressing ZnT7. Quantitative RT-PCR and 35S metabolic labeling analysis demonstrated that over-expression of ZnT7 in RIN5mF cells led to an increase of insulin mRNA expression and subsequent insulin protein synthesis in the cell. Metal-responsive elements (MREs) were identified in the promoter regions of the Ins1 and Ins2 genes. Mtf1, a metal-responsive transcription factor, was shown to specifically bind to the MRE in the Ins genes and activated the insulin gene transcription. Together, the data strongly suggest that ZnT7 plays an important role in regulating insulin expression by modulating Mtf1 transcriptional activity.


Return to top


Connect with ARS Sign up


ARS Home
                            USDA.gov
                            Plain Writing
                            Policies & Links
                            Civil Rights Statements
                            FOIA
                            Accessibility Statement
                            Privacy Policy
                            Non-Discrimination Statement
                            Quality of Information
                            USA.gov
                            WhiteHouse.gov