Nav: Home

Type 2 diabetes is not just about insulin

September 11, 2019

In Switzerland, more than 400,000 people suffer from type 2 diabetes, a serious metabolic disorder that is constantly increasing. Obesity, by promoting the resistance to the action of insulin - one of the hormones that regulate blood sugar levels - is a major risk factor. However, insulin imbalance may not be the only cause of the onset of diabetes. Indeed, researchers at the University of Geneva (UNIGE) have highlighted another mechanism: indeed, the liver appears to have the ability to produce a significant amount of glucose outside of any hormonal signal. In patients with excess liver fat, this overproduction of glucose could lead to type 2 diabetes, regardless of hormonal circuits. These results, published by the Journal of Biological Chemistry, highlight a novel re-reading of the origin of diabetes in overweight patients.

Blood sugar levels are mainly regulated by two antagonistic hormones: insulin, which lowers blood glucose level, and glucagon, which increases it. The liver plays an essential role in regulating blood glucose levels by producing and redistributing glucose under the influence of these two hormones. Overweight people therefore face two threats: on the one hand, the risk of developing insulin resistance, which is a precursor to type 2 diabetes, and on the other hand, an accumulation of fat in liver cells, which is known as "fatty liver" syndrome. This accumulation of lipids indeed induces an alteration in the morphology and structure of mitochondria, the cells energy plants.

"Do these alterations have an effect on mitochondrial function? Is there a link between liver cell mitochondria, obesity and diabetes? To find out, we focused on a protein called OPA1 which, in its "long" form, in other words its non-degraded form, has the function of maintaining the structure of mitochondria," explains Pierre Maechler, professor at the Department of Cell Physiology and Metabolism and at the Diabetes Faculty Centre of the UNIGE Faculty of Medicine, who led this work.

No glucose production without OPA1 protein

Scientists inactivated the OPA1 function in mice to be able to analyze the exact role of mitochondria. "The liver of mice that do not have the long form of OPA1 loses its ability to produce sugar in just a few weeks," says Lingzi Li, a doctoral student in Professor Maechler's laboratory and the first author of the study. "Liver cell mitochondria then show an altered morphology, confirming their importance in sugar metabolism."

An unexpected discovery on the liver

To refine their analysis, Pierre Maechler and colleagues reintroduced a functional OPA1 protein in mice in which it had previously been deleted. "And the mitochondria have regained their normal morphology, but not their activity," the scientists say. "In this area too, shape does not dictate function! It is not enough for mitochondria to appear normal for them to function properly."

However, the greatest surprise was yet to come. "By observing controls, i.e. healthy mice in which OPA1 had been introduced in its long form, we discovered that, when equipped with these "super-mitochondria", they generated more glucose than necessary, and their liver produced sugar without any hormonal call," enthuses Pierre Maechler. This study therefore undermines the long-held belief that the production of glucose by the liver necessarily depends on external stimuli.

This is the first time that glucose production by the liver has been observed independently of an external signal, and particularly hormonal. This finding may explain the development of type 2 diabetes in patients with a "fatty liver" syndrome, apart from any apparent insulin imbalance. To confirm this, UNIGE researchers are now considering modifying the morphology of liver cell mitochondria in overweight mice to see if this overproduction of glucose can trigger abnormally high blood sugar levels and therefore diabetes
-end-


Université de Genève

Related Diabetes Articles:

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.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.