Scientific findings

1. Find new genetic risk factors for diabetes and its complications
We have found that:

• Homeobox transcription factor genes are key players in genetic predisposition to type 2 diabetes (Claussnitzer et al., Cell, 2014)
• The SLC30A8 gene can protect against development of type 2 diabetes (Flannick et al., Nature Genetics, 2014)
• Mutations in PIK3R1 (p85) cause diabetes, lipodystrophy and growth retardation (Chudasama et al., American J Human Genetics, 2013)
• A substantial proportion of individuals in the general population carry low-frequency, nonsynonymous variants in the MODY genes (Flannick et al., Nature Genetics, 2013)

2. Uncover novel disease mechanisms involved in diabetes development
We have uncovered that:

• Novel cell surface markers for white, beige and brown adipocytes may serve asdiagnostically and therapeutically targets in different adipose tissue cell types (Ussar et al., Science Translational Medicine, 2014)
• Protein destabilization, aggregation and degradation are new mechanisms for development of GCK-MODY (Negahdar et al., Molecular Cell Endocrinology, 2014)
• SUMOylation is a novel mechanism for regulation of the diabetes-associated enzyme and glucose sensor glucokinase (Aukrust et al., J Biological Chemistry, 2013)
• Clock genes in adipose tissue play a role in metabolic adaptation to a history of weight cycling and increased fat mass (Dankel et al., American J Physiology, 2013)
• Urinary betaine can act as a marker of diabetes in cardiovascular patients (Schartum-Hansen et al., PLoS One, 2013)
• Transcriptional co-regulators are important regulators of systems metabolism (York et al., Molecular Endocrinology, 2013)

3. Develop and implement targeted and improved treatment of diabetes
We have:

• Found that 1.1% of patients in the Norwegian Childhood Diabetes Registry actually have monogenic diabetes (Irgens et al, Diabetologia, 2013)
• Made human induced pluripotent stem cells (hiPSCs) for several MODY forms (Teo et al., J Biological Chemistry, 2013)
• Discovered that the rare variant E508K in HNF1A causes a phenotype in Mexicans that can be misdiagnosed as type 2 diabetes (Estrada, Aukrust, Bjørkhaug et al., JAMA, 2014)

The latter finding is an example of the way our KG Jebsen Center works:
Identify a gene variant ‒ find the mechanism of action ‒ provide the possibility of
targeted and improved treatment.