Peter Bergsten

Mechanisms of lipotoxicity in beta cells

The major focus of Peter Bergsten’s research group is mechanisms of lipotoxicity in beta cells. The aim is addressed in in vitro studies by using various cell and molecular biology techniques but also in in vivo studies by measuring the level of circulating free fatty acids, hormones and inflammatory markers.

Bild på medlemmar i forskargruppen

Cells & Islets

At the cell level, we work to further the understanding of the function of beta cells and alpha cells in human pancreatic islets. Free fatty acids (FFAs) function as the main energy source for most of the tissues in the body except for the brain. A certain level of FFAs is essential for glucose stimulated insulin secretion (GSIS). Our work addresses the relationship between FFAs and islet function. At the beta cell level, our findings suggest that long chain FFAs acutely induce insulin secretion from human islets at physiologically fasting glucose concentrations, with monounsaturated fatty acids (MUFAs) being more potent than saturated fatty acids (SFAs). In vitro short exposure of alpha cells and islets to elevated FFA levels stimulate glucagon secretion, while prolonged exposure inhibits the secretion of glucagon. Based on our experimental results we create models for FFA-induced hyperinsulinemia and hyperglucagonemia in human islets and various cell lines.

Metformin is the first-line treatment for patients with T2DM, recently increasingly introduced for treatment of obese children and adolescents. We investigate whether metformin has beneficial effects on FFA-treated islets, preventing them from early hypersecretion and later decrease both insulin and glucagon secretion through normalizing oxygen consumption rate (OCR) and other mechanisms.

Clinical & Patient

At the clinical level, we are working to increase the understanding of risk factors and treatments of childhood obesity. In 2010 the recruitment for the ULSCO (Uppsala Longitudinal Study of Childhood Obesity) cohort began The cohort includes obese patients and lean controls, aged under 18. This cohort is followed via yearly functional tests, such as glucose tolerance tests. ULSCO serves as an important resource in defining and understanding factors contributing to childhood obesity.

GLP-1 is an incretin hormone secreted in response to a meal; it increases satiety and stimulates insulin secretion. GLP-1 analogs are used for the treatment of type 2 diabetes. Because of their effects on satiety, they are also increasingly being used in the treatment of obesity. The Combat-JUDO study was a six-month, double-blind, multi-center randomized controlled trial performed between September 2015 and September 2016. Eligible children and adolescents with obesity were recruited and randomly assigned to receive weekly injections of either exenatide (a GLP-1 analog) or placebo. The study found that exenatide was well tolerated and led to a reduction of BMI. We are still exploring the beneficial effects of GLP-1 analogs in the treatment of obesity.

Clinically, we have noticed beneficial effects on obesity from the anti-diabetes drug metformin. Currently, we are starting up a randomized clinical trial at Akademiska Children’s Hospital investigating the treatment potential of metformin for obesity. This study is registered as the MINT study.

Society & Prevention

At the societal level, we are working with several projects to prevent childhood obesity in communities. The first project which UU is a formal part of is Swelife’s strategic innovation project ”Ending CHildhood Obesity” (ECHO)( website: https://swelife.se/pbf/ ). Beginning in the summer of 2021, Peter Bergsten will be head project manager and lead the project towards the goal of zero childhood obesity at school start by 2030. ECHO is a national project aiming to prevent overweight and obesity among children 0-6 years old, thus improving their physical and mental wellbeing and halting the current increase of type 2 diabetes and cardiovascular diseases. ECHO wants to shift society’s focus to health rather than disease through a system transformation with a healthy-risk-disease perspective. The project has 24 official partners and a broad network of actors working with the individuals, health care, academia and the business sector to secure every child’s right to have an equal and healthy upbringing. The solutions provided by the project are intended to be nationally scalable.

To achieve a sustainable solutions in society the project will initiate a collaboration with five Swedish municipalities and their regions in 2021. Further, this will be expanded to 50 municipalities in 3 years, and lastly all 290 municipalities and 21 regions.

During the spring of 2021, the group contributed to two innovation competitions, so called Hackathons. A global one run by SAS Institute and one that was part of ECHO’s Grand Challenge. The contribution from Peter Bergsten’s group was an idea to design a digital city twin of a Swedish municipality and its region to drive society towards prevention of disease, and thus improving child health. A digital twin is a virtual replica used to follow trends and developments in society by collecting data and using analytical methods such as artificial intelligence and machine learning. In the global competition, the digital twin got a shared first place in the category Health / Childhood obesity together with the team "Tupã Fit" from Brazil. In the national competition, digital twin came in the top 5 and thus advanced to the next stage of the ongoing competition.

For more information about team digital city twin ://communities.sas.com/t5/Hacker-s-Hub-library/Digital-Community-Twin-Community-Twins-Improving-Health/ta-p/730336

The group works in close collaboration with the Finnish city Seinäjoki and the Finnish Health and Welfare Institute to evaluate the intervention to reduce childhood obesity in Seinäjoki.

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