Table of Contents
The Unveiled Relationship Between Zinc and Diabetes – A Scientific Breakthrough on the Mechanistic Link
Investigators have identified a critical relationship between levels of zinc in human physiology and the diminished risk for type 2 diabetes and fatty liver disease. The research, published in the journal eLife, suggests that a particular loss-of-function mutation in the zinc transporter protein known as SLC39A5 is correlated with increased zinc levels. This leads to decreased susceptibility to diabetes, reduced insulin resistance, and less accumulation of liver fat in genetically altered mice. This points to SLC39A5 as a likely candidate for targeted therapy for these ailments.
Through genetic analyses in both human and murine models, a zinc transporter has been pinpointed as a potential focus for treatments aimed at type 2 diabetes and fatty liver disease.
The investigation has found a causal link between human zinc levels and the likelihood of developing type 2 diabetes and fatty liver disease. This study, which was recently published in eLife, has been lauded by its editors as a foundational research piece that significantly augments our comprehension of the metabolic role of zinc.
The researchers amassed robust evidence via cutting-edge genetic analysis involving a sizable cohort of human participants, along with comprehensive laboratory research focused on a potential treatment target for non-alcoholic fatty liver disease and type 2 diabetes. The findings will attract attention from researchers focused on both metabolism and the biology of trace elements.
Numerous lines of proof converge to suggest that zinc is pivotal in the production of insulin and the metabolism of glucose. “It is known that augmenting zinc consumption leads to better control of blood glucose levels in individuals with prediabetes or type 2 diabetes, and individuals with a mutation in a critical zinc transporter protein exhibit a lower risk of diabetes,” states Shek Man Chim, Principal Scientist at Regeneron Pharmaceuticals, Inc., New York, US. “Nevertheless, the precise mechanisms by which zinc affects systemic blood glucose levels and the risk of diabetes remain to be elucidated.”
To delve into the protective role of zinc against diabetes, Chim and his team conducted experiments involving loss-of-function mutations, based on genetic sequence data gathered from a large group of European ancestry participants in the Regeneron Genetics Center-Geisinger Health System DiscovEHR study. This led to the identification of a rare mutation causing a loss of function in the SLC39A5 zinc transporter protein, which was related to increased circulating zinc levels.
In a follow-up, a meta-analysis of four studies that included a multi-ethnic European and US sample comprising over 62,000 diabetes cases and over 518,000 healthy controls was carried out. This reinforced the findings that carriers of the SLC39A5 loss-of-function mutation had elevated levels of circulating zinc and were less likely to develop diabetes.
Having established the SLC39A5 transporter as a crucial clinical nexus between zinc and diabetes, the researchers engaged in further exploration by engineering mice that lacked this particular protein. Predictably, these mice displayed heightened levels of blood and tissue zinc. Subsequent experiments revealed that these mice, when subjected to a diet high in fat and fructose, showed a significant decrease in fasting glucose levels in comparison to control mice.
Since diabetes often occurs alongside non-alcoholic fatty liver disease, further investigations were carried out to determine if the absence of SLC39A5 had protective effects on the liver. The studies confirmed that mice devoid of SLC39A5 had reduced liver fat accumulation and markers of liver damage.
The team also probed the protective role of SLC39A5 absence against the progression of non-alcoholic fatty liver disease to the more severe non-alcoholic steatohepatitis (NASH). The results demonstrated reduced markers of liver damage, decreased fasting blood glucose levels, and improvement in liver inflammation and fibrosis in mice lacking SLC39A5.
A concern raised by public reviewers was the unclear metabolic differences observed in male and female mice upon inactivation of SLC39A5. Additional research is required to examine this further and to better understand the role of SLC39A5 in pancreatic cell function and glucose tolerance.
“In summary, our research offers first-time genetic evidence substantiating the protective influence of zinc in mitigating high blood sugar levels and reveals the underlying mechanistic foundation for this effect,” states Harikiran Nistala, currently Head of Functional Genomics at Alkermes Inc, Waltham, US. “Our findings indicate that inhibiting SLC39A5 could serve as a viable therapeutic approach for type 2 diabetes and other conditions where zinc supplementation is insufficient.”
Reference: “Genetic Inactivation of Zinc Transporter SLC39A5 Enhances Liver Function and Reduces Hyperglycemia in Obesogenic Environments” by Shek Man Chim, Kristen Howell, John Dronzek, Weizhen Wu, Cristopher Van Hout, Manuel Allen Revez Ferreira, Bin Ye, Alexander Li, Susannah Brydges, Vinayagam Arunachalam, Anthony Marcketta, Adam E Locke, Jonas Bovijn, Niek Verweij, Tanima De, Luca Lotta, Lyndon Mitnaul, Michelle G. LeBlanc, David Carey, Olle Melander, Alan Shuldiner, Katia Karalis, Aris N. Economides, and Harikiran Nistala, published on 18 September 2023 in eLife. DOI: 10.7554/eLife.90419.1.
Frequently Asked Questions (FAQs) about Zinc and Diabetes Link
What is the main focus of the research published in eLife?
The main focus of the research is to explore the relationship between zinc levels in humans and the reduced risk of type 2 diabetes and fatty liver disease. It particularly investigates the role of a zinc transporter protein called SLC39A5 as a potential therapeutic target for these conditions.
What is SLC39A5 and why is it important?
SLC39A5 is a zinc transporter protein. In this study, a specific loss-of-function mutation in SLC39A5 was found to be associated with elevated levels of zinc in the body. This elevation in zinc levels led to a reduced risk of type 2 diabetes and fatty liver disease, making SLC39A5 a potential target for future therapies.
Who conducted the research and who are the target audience?
The research was conducted by a team of scientists led by Shek Man Chim, Principal Scientist at Regeneron Pharmaceuticals, Inc., and Harikiran Nistala, Head of Functional Genomics at Alkermes Inc. The target audience includes researchers in the fields of metabolism, biology of trace elements, and clinicians focusing on type 2 diabetes and fatty liver disease.
How was the research carried out?
The research involved a large-scale genetic analysis of human participants, as well as comprehensive lab studies using genetically engineered mice. Further analysis also included meta-studies involving multi-ethnic European and U.S. samples.
What are the potential applications of this research?
The findings suggest that targeting the SLC39A5 protein could be a potential therapeutic strategy for treating type 2 diabetes and fatty liver disease. This could pave the way for new medications or treatment protocols that focus on zinc metabolism.
Are there any limitations or areas that require further investigation?
Yes, the study pointed out that the metabolic consequences of SLC39A5 inactivation between male and female mice remain unclear. Additionally, further research is required to fully understand the role of SLC39A5 in pancreatic cell function and glucose tolerance.
What are the key findings regarding the role of zinc?
The study found that zinc plays a crucial role in insulin production and glucose metabolism. Elevated levels of zinc, correlated with the loss-of-function mutation in the SLC39A5 protein, led to decreased susceptibility to diabetes and reduced insulin resistance.
What does the study conclude?
The study concludes that zinc has a protective role against high blood sugar levels and reveals the mechanistic basis for this effect. It suggests that inhibiting SLC39A5 could serve as a viable therapeutic approach for type 2 diabetes and related conditions.
More about Zinc and Diabetes Link
- eLife Journal Study on Zinc and Diabetes
- Regeneron Pharmaceuticals, Inc.
- Alkermes Inc Functional Genomics
- Type 2 Diabetes Overview
- Fatty Liver Disease Information
- Meta-Analysis in Medical Research
- Insulin Resistance: An Overview
- Genetic Analysis Techniques
- Role of Zinc in Human Health
