Diabetes Type 2
The research group has a long tradition of diabetes research. The strength of the group is the integration of clinical and basic research.
Research group leader
Karolinska University Hospital Solna
SE-171 76 Stockholm
The project aims at elucidating the pathogenesis of type 2 diabetes and developing therapies for the disease. The main areas studied are:
1) Molecular mechanisms behind impaired islet hormone secretion.
2) The mechanism behind insulin resistance.
3) Genetic defects in type 2 diabetes.
4) Novel approaches to the treatment of type 2 diabetes.
5) Prevention of IGT (impaired glucose tolerance) and type 2 diabetes. In our studies we use well-defined groups of healthy subjects and patients, together with animal models of diabetes (ob/ob mice, GK rats etc.).
6) In studies of islet dysfunction in GK rats we have shown multiple defects in glucose metabolism.
7) We plan to study the role of islet tyrosine phosphatases and glucose-6-phosphatase in this context. Additional factors to be studied are impaired signalling through the adenyl cyclase(cAMP, PKA, AKAPs) and PKC pathways, as well as glucocorticoid receptors, gluco- and lipotoxicity. We will specifically focus on mechanisms regulating exocytosis of hormones.
8) Long-chain fatty acid CoA plays a key role in the development of insulin resistance. We are therefore investigating the regulation of free fatty acid oxidation in muscle by studying the expression and activities of malonyl-CoA, ACC2, AMP kinase, malonyl-CoA decarboxylase and UCP-3. To identify diabetes genes, we are investigating candidate genes selected from chromosomal regions linked to type 2 diabetes and genes that are relevant for the disease on the basis of biological functions. For each gene, we study at least one marker using PCR-DASH SNP genotyping assays.
9) Imidazoline BL11282 and GLP-1 stimulate glucose-induced but not basal insulin release, minimizing the risk of hypoglycaemia. To find novel treatment of diabetes, we are isolating and characterizing substances from extracts of traditional herbal drugs in collaboration with scientists in Vietnam and Malaysia.
10) Our ambition is to characterize the imidazoline receptor in B-cells to facilitate the clinical development of these compounds and introduce GLP-1 in the treatment of severely ill patients with hyperglycaemia.
11) A ten-year project aimed at population-based primary prevention of type 2 diabetes has been under way since 1995 in three municipalities of Stockholm County (Sigtuna, Upplands Väsby and Värmdö).
12) The prevention comprises lifestyle intervention, such as increasing physical activity and decreasing tobacco use and overweight among the adult population. In the initial phase, a cross-sectional baseline study of 8,000 men and women was carried out, and the cohort has been subjected to a follow-up study after a period of ten years, 2003-2006. In the baseline study, about 450 new cases of diabetes and IGT were detected, and odds ratios of risk factors such as diabetes heredity, overweight, low birth weight, tobacco and alcohol use, and psychosocial stress have been presented. The purpose of the follow-up study is both to evaluate the impact of the prevention and to further assess the significance of risk factors.
Members of the group
Inspirational lecture: Claes-Göran Östenson
Who is at risk of Type 2 Diabetes?
Claes-Göran Östenson, Professor of Endocrinology at the Department of Molecular Medicine and Surgery, from the seminar series for students 'Get inspired by a professor'