Intestinal hormone study to pave way for future interventions in treatment of obesity and type 2 diabetes
The hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like polypeptide-1 (GLP-1), which are produced and secreted after a meal, have proven to have a positive effect on glycaemic control and on body weight in patients with type 2 diabetes.
However, more needs to be learnt about the mechanisms underlying the effect of GIP and GLP-1, as recent research has been generating debate as to whether increased or decreased GIP receptor (GIPR) activity is more effective in the treatment of type 2 diabetes in combination with GLP-1 receptor agonists.
In her PhD project, which will be based at the University of Copenhagen’s Department of Biomedical Sciences, Hüsün Sheyma Kizilkaya - who completed her Master’s in Human Biology in 2017 – will try to provide better insight into GIPR. The Danish Diabetes Academy has awarded DKK 1.1 million to the project.
Great expectations: new knowledge and insight
More than 20 naturally occurring GIPR variants have been identified in a cohort of Danes living with type 2 diabetes, but only a few variants have so far been characterized. The aim of the PhD project is therefore to characterize these variants with reference to ligand binding, receptor signalling and internalization, and also to investigate phenotypic properties such as BMI, insulin resistance and type 2 diabetes in people with these variations. Hüsün Sheyma Kizilkaya will then use different cell lines to study the link between the GIPR and GLP-1R systems and to investigate the synergistic effect between them in the treatment of type 2 diabetes.
‘We expect the project to provide new knowledge concerning naturally occurring GIPR mutations and their importance in metabolic diseases, and thereby to enhance understanding of the GIP system in these diseases. At the same time, the project will shed light on the interaction between the GIP and GLP-1 systems, and pave the way for future development of GIP and GLP-1 interventions in the treatment of obesity and type 2 diabetes’, says Hüsün Sheyma Kizilkaya.
Six months in the USA
The principal supervisor of the project is Professor Mette M. Rosenkilde. She and Hüsün Sheyma Kizilkaya are already acquainted, as Hüsün Sheyma Kizilkaya has been a research assistant at the University of Copenhagen’s Department of Biomedical Sciences since May 2019. In recent months, the two have been planning the project and making initial preparations in collaboration with Associate Professor Niels Grarup of the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, who will also step in with supervision along the way.
There will be an interesting international element to the project in the form of a six-month visit to Duke University in Durham, USA, where Hüsün Sheyma Kizilkaya will work under the supervision of Professor Christopher B. Newgard at Duke Molecular Physiology Institute.
‘After completing my PhD, I would like to continue my career with a postdoc abroad, where I can carry on working on metabolic disease and translational medicine’, says Hüsün Sheyma Kizilkaya.
By Pernille Fløjstrup Andersen, Communications Officer, DDA
Hüsün Sheyma Kizilkaya, born 1989
Has been awarded DKK 1.1 million by the Danish Diabetes Academy.
PhD project title: Impact of naturally occurring GIPR variants for GIPR function and interplay with GLP-1R
Research centres: Department of Biomedical Sciences, University of Copenhagen / Duke University Medical Center, Durham, USA
Contact +45 4050 2056
Contact Danish Diabetes Academy
Managing Director Tore Christiansen
Phone: +45 2964 6764