Soluble leptin receptor - Clinical and mechanistic studies to explore the relationship with insulin resistance and glucose metabolism

Plasma soluble leptin receptor (sOb-R) seems protective of gestational and type 2 diabetes in observational studies, but the mechanisms are unknown. sOb-R is formed by ectodomain shedding of membrane-bound leptin receptors (Ob-Rs), and evidence suggest that sOb-R reflect the amount of membrane bound leptin receptors, and thereby reflect efficient leptin signaling. We aim to understand the mechanisms linking sOb-R to insulin resistance and diabetes, and how sOb-R levels are affected by diabetes-releated traits, in order to improve prevention and treatment of type 2 diabetes.

We combine results from several observational, interventional, in vitro and Mendelian Randomization designs. We use mixed models regression to model sOb-R response to physical activity, a lunch meal, and hyperinsulinemia. Mixed models regression is also used for multilevel analysis of associations between sOb-R and diabetes-related traits across the different clinical studies.

In 2020, we have added two-sample Mendelian Randomization studies to substantiate our findings.

Primary Investigator: Christine Sommer

Co-investigators/participants
Kåre I. Birkeland
Cecilie Wium
Kjersti G. Vangberg
Hanne L. Gulseth
Ingvild Blom-Høgestøl
Anne-Karen Jenum
Line Sletner
Sindre Lee-Ødegård
Gunn-Helen Moen

External collaborators
Christian Drevon
Jørgen Jensen
Arild Rustan
Natasa Nikolic