Study decodes gene function that protects against type 2 diabetes

November 04, 2019

Type 2 diabetes affects almost 400 million people across the world. It is caused by a combination of lifestyle as well as genetic factors which together result in high blood sugar levels.

One such genetic factor is a variation in a gene called SLC30A8, which encodes a protein which carries zinc. This protein is important, because zinc is essential for ensuring that insulin, (the only hormone that can reduce blood sugar levels) has the right shape in the beta-cells of the pancreas.

Researchers have known for almost ten years that changes in this gene can reduce the risk of getting type 2 diabetes, but not how this happened. They now recruited new members from families with a rare mutation in the SLC30A8 gene to study how they responded to sugar in a meal.

"A definite strength of our study is we could study families. We could compare people with the mutation with their relatives who do not have the mutation, but who have similar genetic background and life-style", said Departmental chief doctor Tiinamaija Tuomi from the Helsinki University Hospital, who co-led the study.

"This way, we could make sure that the effects we were seeing were definitely because of this gene, and not because of another genetic or life-style factor."

The results showed that people with the mutation have higher insulin and lower blood sugar levels, reducing their risk for diabetes.

An international collaboration of 50 researchers also studied pancreatic cells with and without the mutation in the lab, and carried out experiments in mice and human cellular material to understand exactly what was happening when the function of the SLC30A8 gene changed.

"The work is a collaborative effort bringing pharma and academia together and researchers from multiple European Countries. It is a tour de force, since we were able to measure the impact of the mutation in many different systems, including human beta-cells", said Professor Anna Gloyn, who co-led the study, from the Wellcome Centre for Human Genetics, University of Oxford.

"We found that this mutation had collateral consequences on key functions of pancreatic beta cells and during their development. Importantly, this study exposes the extraordinary molecular complexity behind a specific gene variation conferring risk or protection from type 2 diabetes", said Dr Benoit Hastoy, co-first author from the Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford.

"Taken together, the human and model system data show enhanced glucose-stimulated insulin secretion combined with enhanced conversion of the prehormone proinsulin to insulin as the most likely explanation for protection against type 2 diabetes", said Om Prakash Dwidedi, the co- first author of the study from the Institute for Molecular Medicine Finland (FIMM), University of Helsinki.

Better understanding of the genetic and pathological mechanism behind diabetes can open up new ways of preventing or treating type 2 diabetes.

"Our results position this zinc transporter as an appealing and safe target for antidiabetic therapies. If a drug can be developed that mimics the protective effect of this mutation, beta-cell function could be preserved and the insulin secretion capacity in diabetic patients maintained", said Professor Leif Groop from the University of Helsinki and the Lund University who directed the study.
-end-
The study was done in collaboration with researchers from the University of Helsinki, Helsinki University Hospital, Folkhälsan Research Center, Lund University, University of Oxford, Imperial College London as well as Pfizer Inc. and Regeneron Pharmaceuticals.

University of Helsinki

Related Diabetes Articles from Brightsurf:

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.