A5067689472- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Liver Disease Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- FOXO transcription factor regulation
- RNA modifications and cancer
- Diet, Metabolism, and Disease
- Mechanisms of cancer metastasis
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- Wnt/β-catenin signaling in development and cancer
- Sirtuins and Resveratrol in Medicine
- Genomics and Rare Diseases
- Hedgehog Signaling Pathway Studies
- Diabetes Treatment and Management
- Genetic Associations and Epidemiology
- Heat shock proteins research
University of Bergen
2013-2024
Max Planck Institute for Metabolism Research
2022-2023
Joslin Diabetes Center
2016-2023
Harvard University
2016-2023
Haukeland University Hospital
2013-2017
Ectopic lipid accumulation in the liver is an almost universal feature of human and rodent models generalized lipodystrophy also a common type 2 diabetes, obesity, metabolic syndrome. Here we explore progression fatty disease using mouse model created by fat-specific knockout insulin receptor (F-IRKO) or both IR insulin-like growth factor 1 (F-IR/IGFRKO). These mice develop severe lipodystrophy, hyperlipidemia, within first weeks life. By 12 age, demonstrated increased reactive oxygen...
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is central to the action of insulin and many growth factors. Heterozygous mutations in gene encoding p85α regulatory subunit PI3K (PIK3R1) have been identified patients with SHORT syndrome — a disorder characterized by short stature, partial lipodystrophy, resistance. Here, we evaluated whether syndrome–associated PIK3R1 account for pathophysiology that underlies abnormalities generating knockin mice are heterozygous Pik3r1Arg649Trp...
The CEL gene encodes the digestive enzyme carboxyl ester lipase. CEL-HYB1, a hybrid allele of and its adjacent pseudogene CELP, is genetic variant suggested to increase risk chronic pancreatitis (CP). Our aim was develop mouse model for CEL-HYB1 that enables studies pancreatic disease mechanisms.
Abstract Hepatocyte nuclear factor-4 alpha (HNF-4A) regulates genes with roles in glucose metabolism and β-cell development. Although pathogenic HNF4A variants are commonly associated maturity-onset diabetes of the young (MODY1; HNF4A-MODY), rare phenotypes also include hyperinsulinemic hypoglycemia, renal Fanconi syndrome liver disease. While association functionally damaging HNF1A HNF1A-MODY type 2 is well established owing to robust functional assays, impact on HNF-4A transactivation...
Phosphatidylinositol 3-kinase (PI3K) plays a central role in insulin signaling, glucose metabolism, cell growth, development, and apoptosis. A heterozygous missense mutation (R649W) the p85α regulatory subunit gene of PI3K (PIK3R1) has been identified patients with SHORT (Short stature, Hyperextensibility/Hernia, Ocular depression, Rieger anomaly, Teething delay) syndrome, disorder characterized by postnatal growth retardation, resistance, partial lipodystrophy. Knock-in mice same mirror...
The genetic disease architecture of Inuit includes a large number common high-impact variants. Identification such variants contributes to our understanding the aetiology diseases and improves global equity in genomic personalised medicine. We aimed identify characterise novel genes associated with Maturity Onset Diabetes Young (MODY) Greenlandic population.Using combined data from population cohorts 4497 individuals, including 448 whole genome sequenced we screened 14 known MODY for...
To determine the ocular consequences of a dominant-negative mutation in p85α subunit phosphatidylinositol 3-kinase (PIK3R1) using knock-in mouse model SHORT syndrome, syndrome associated with short stature, lipodystrophy, diabetes, and Rieger anomaly humans.We investigated mice heterozygous for changing arginine 649 to tryptophan physical examination, optical coherence tomography (OCT), tonometry, histopathologic sections from paraffin-embedded eyes, compared findings similar investigations...
The transcription factor hepatocyte nuclear factor-1α (HNF-1A) is involved in normal pancreas development and function. Rare variants the HNF1A gene can cause monogenic diabetes, while common confer type 2 diabetes risk. precise mechanisms for regulation of HNF-1A, including role function post-translational modifications, are still largely unknown. Here, we present first evidence HNF-1A being a substrate SUMOylation cellulo identify two lysine (K) residues (K205 K273) as sites....
Class Ia phosphoinositide 3-kinases (PI3K) are critical mediators of insulin and growth factor action. We have demonstrated that the p85α regulatory subunit PI3K modulates unfolded protein response (UPR) by interacting with regulating nuclear translocation XBP-1s, a transcription essential for UPR. now show activity is required full activation Pharmacological inhibition in cells blunts ER stress-dependent phosphorylation IRE1α PERK, decreases induction ATF4, CHOP, XBP-1 upregulates UPR...
Non-alcoholic fatty liver disease (NAFLD) is a manifestation of metabolic syndrome, and estimated to affect one billion individuals worldwide. An increased intake high-fat diet (HFD) sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined promotes progression more severe form injury unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform increases endoplasmic reticulum (ER) stress in dose dependent fashion, so when coupled with HFD...
Correctly diagnosing MODY is important, as individuals with this diagnosis can discontinue insulin injections; however, many people are misdiagnosed. We aimed to develop a robust approach for determining the pathogenicity of variants uncertain significance in hepatocyte nuclear factor-1 alpha (HNF1A)-MODY and obtain an accurate estimate prevalence HNF1A-MODY paediatric cases diabetes.We extended our previous screening Norwegian Childhood Diabetes Registry by 830 additional samples...
The transcription factor Hepatocyte nuclear factor-1α (HNF1A) is important for normal pancreas development and function. Some HNF1A genetic variants are associated with type 2 diabetes, others can cause Maturity-Onset Diabetes of the Young (MODY3). Since variations in gene give different clinical consequences, novel sequence require thorough functional analysis. Here we investigate, vitro, consequence rare non-coding intronic from Norwegian MODY registry. To evaluate effect four potential...