Prof. Peter Bergsten, Department of Medical Cell Biology, Uppsala University and adjunct professor at Uppsala University Children´s Hospital, Sweden and Dr. Hjalti Kristinsson, Department of Medical Cell Biology, Uppsala University, Sweden
Title: Mechanisms of type-2-diabetes development during childhood and adolescent obesity
ABSTRACT: Every fourth to fifth Icelandic and Swedish child has overweight or obesity, which puts them at risk of developing type 2 diabetes mellitus (T2DM) and other complications early in life. With these comorbidities already present in children the consequences for the affected individuals and society are considerable. So far no strategy to combat childhood obesity has proven to be effective and sustainable. To address this challenge we used a translational approach with a childhood obesity cohort and isolated islets of Langerhans. We identified insulin hypersecretion in children with obesity as a risk factor for developing T2DM and attempts to normalize insulin secretion were made. Strategies to identify ways of normalizing insulin hypersecretion, first studied in the isolated islet of Langerhans, involved both targeted approaches (role of free fatty acids, mitochondrial respiration, pharmacological substances used for treatment of T2DM and/or obesity) and un-targeted approaches (lipidomics, transcriptomics and proteomics). Promising novel strategies to normalize insulin hypersecretion were then translated into the children with obesity in a RCT format with the aim of increasing treatment alternatives for this patient group, where pharmacological alternatives are scarce. A community-based approach to improve childhood health has also been initiated, the Ending ChildHood Obesity (ECHO) zone. In the ECHO zone focus is on changing the environment of the child into one which promotes healthy lifestyle with regard to physical activity, eating and sleep, i.e. making it easy for the child to make healthy choices. In order to be sustainable ECHO zones require long-term (>10 years) commitment from (local) government. After such decisions have been made, the intervention is detailed and also data collecting. Data, which are collected at societal, family and individual level, will enable to create evidence for what components of the intervention are necessary for effective and sustainable improvement in childhood health.
The focus in Peter Bergsten´s talk will be on “Insulin hypersecretion during childhood obesity - role of free fatty acids - plausible ways of intervention”
The focus in Hjalti Kristinsson´s talk will be on “Free fatty acid palmitate and its effects on pancreatic islet cell hormone secretion, function and metabolism - cells that secrete or die trying”.
Time: Thursday, October 4th, 11.00-12.00
Location: Fróði auditorium, Sturlugata 8
BIOSKETCH: Peter Bergsten obtained his medical training at Uppsala University, Sweden. In parallel he conducted research addressing how secretory mechanisms of the islet of Langerhans are affected in type 2 diabetes. After receiving his PhD in 1987 he was an International Fogarty Fellow at the NIH, USA, and also spent a postdoctoral stay in Cambridge, UK. In 2008 he was appointed full professor at Uppsala University. At this time he had started to combine mechanistic cellular work with clinical studies in a childhood obesity cohort at the Uppsala University Children’s Hospital, where he is also adjunct professor. His translational research addressing obesity and obesity-related complications in children with obesity and isolated human islets has focused on several aspects including insulin and glucagon secretion, circulating fatty acid levels and incretin GLP-1. The incretin was also the focus of a clinical trial led by him. In recent years he has started community-based preventive work addressing childhood health by initiating the intervention strategy Ending ChildHood obesity (ECHO) zone. He has published over 100 original articles and received several research awards. He is scientific coordinator of the multidisciplinary European Commission project “Beta-cell function in juvenile type 2 diabetes and obesity” (Beta-JUDO), and board member of several scientific societies, journals and funding organizations.
Hjalti Kristinsson has a MSc. in pharmacy from the University of Iceland in 2008. His master project in the pharmacy program was done at ORF genetics where he studied glycosylation of human proteins transgenically expressed in barley. He then spent over three years at the Icelandic Medicines Agency. In 2012 he graduated from Uppsala University with a MSc. degree in Biomedicine. In his master project he was supervised by Professor Peter Bergsten and focused on the effect of Free fatty acid receptor 1 antagonism during lipotoxicity in beta-cells, a collaborative project with Astra Zeneca. He graduated in 2017 with a Ph.D. from the faculty of medicine, department of medical cell biology, with the thesis name of Effects of free fatty acids on insulin and glucagon secretion. During his PhD thesis work Hjalti worked within the European project BetaJUDO (beta-cell function in juvenile diabetes and obesity, FP7). During this time his research was on pancreatic islet cell models of obesity and Type-2 diabetes development as well plasma samples from the Uppsala longitudinal study of childhood obesity (ULSCO). His focus has been on the role of FFAR1 in insulin and glucagon secretion in the obese state where fatty acid levels are elevated. Part of his research within this scope has involved combining different "omics" analysis from cell studies. He has also published findings from beta-cell studies on how the fatty acid sensing G-protein coupled receptor FFAR1 signals to enhance mitochondrial respiration and insulin secretion demonstrating how long-chain fatty acids act both as signaling molecules for enhanced metabolism and as fuel substrates. Hjalti currently holds a position in Professor Bergsten’s group as a researcher at the Department of Medical Cell biology at Uppsala University.