Zinc Nexus: Unravelling the Threads of Diabetes and Inflammatory Bowel Disease

 

Zinc Nexus: Unravelling the Threads of Diabetes and Inflammatory Bowel Disease

Speaker: Professor Christer Hogstrand, Professor of Molecular Ecotoxicology in the Department of Analytical, Environmental and Forensic Sciences at King's.

Abstract: 

Zinc was known to the Greeks and Romans 20 BCE, but it took until 1974 before it was recognised as an essential element to man. Since then, we have learned that 1/3 of all human proteins bind zinc and that it carries out functions as a signalling ion, much akin to Ca²⁺ but at much lower concentrations. We also know now that zinc is involved in almost all biological processes. In this talk I will focus on our work to understand the roles of zinc in glucose homeostasis, and in maintaining the integrity of the intestinal epithelium. Pancreatic β-cells have among the highest concentrations of zinc in the body. Most of the zinc in these cells is found in insulin granules where some of it is used to bind insulin. The transporter that delivers zinc to the insulin granules, ZnT8 (SLC30A8), has a common W325R polymorphism in the C-terminal domain, which increases the risk to develop type 2 diabetes. We now have some knowledge about the function of ZnT8 and how the W325R polymorphism influences susceptibility to develop type 2 diabetes. β-cell function is also dependent on zinc importers of the ZIP (SLC39) family of proteins and reduced expression of ZIP6 is associated with type 2 diabetes. Knockout of Slc39a6 in MIN6 cells severely affects their function with effects on β-cell markers. Zinc transporters are also critically important in the intestine and not only for systemic zinc uptake but also for intestinal epithelial function. Using a combination of mice models, ileum organoids from mouse and human and Caco-2 cells we discovered that zinc contributes to maintenance of intestinal barrier function by regulating expression of tight junction genes and proteins as well as mucin. This function is dependent on dietary agonists of the Aryl Hydrocarbon Receptor (AHR), which controls expression of key zinc importers. The dietary AHR agonists that are critical for this function are indoles and tyrosine derivates enriched in cruciferous plants. Giving mice zinc and the plant-derived AHR agonist, indole-3-carbinol, protected them from Dextran Sodium Sulfate induced inflammatory bowel disease.

Biography: 

Professor Christer Hogstrand (CH) has a B.Sc. in Biology (1985) and a Ph.D. in Zoophysiology (1991) from the University of Gothenburg, Sweden. Having finished his PhD, he spent two years as Research Fellow at McMaster University, Canada. In 1994, CH took a position as Assistant Professor in Biology and Toxicology at the University of Kentucky, USA. He was promoted to Associate Professor in 1999 but moved to the UK to become Lecturer at King's College London. In 2001, he was promoted to Reader and in 2005 to Professor. Between 2004 and 2014 he was Sub-Dean for Post-Graduate Taught Education. He then took on the role as International Lead for the School of Life Course and Population Sciences (2018 – 2021) and was a member of the Executive Committee of the School. In 2022, he moved to the School of Cancer and Pharmaceutical Sciences to become Head of the Department for Analytical, Environmental and Forensic Sciences.

He has held appointments as senior investigator at the University of Miami, USA, and at the National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway. CH is also an Expert for the European Food Safety Authority (Parma, Italy) since 2004 and presently vice-chair of its Panel on Contaminants in the Food Chain (Contam).

Date: Friday 10 May 2024

Time: 12pm - 1pm

Format: Hybrid meeting. Seminar Room, second floor, Hodgkin building Guy’s campus and online.