Hormone secretion

Head: Bo Ahrén

Group members

Bo Ahrén, PI, MD, Professor
Lena Ohlsson, Research scientist
Bilal Omar, Research scientist
Wathik Alsalim, MD, PhD student
Linda Ahlqvist, PhD student
Ola Lindgren, MD, PhD student
Johan Fargren, MD
Kristina Andersson, BMA
Catarina Blennow, BMA
Gustav Dahl, Research Nurse

Type 2 diabetes is a commom disease predisposing to a number of associated conditions, such as cardiovascular diseases. It is caused by a combination of insulin resistance and defective islet function. The aim of this project is to characterise the regulation of islet function, both insulin and glucagon secretion, how it is compensatorily adapted to insulin resistance, and how this regulation fails during development of diabetes. The project also develops new treatment for type 2 diabetes by a combination of techniques, and is at present focused on the use of GLP−1 (glucagon−like peptide−1) in the treatment. Particularly, the project studies the target of inhibiting the inactivation of GLP−1 by inhibiting the activity of the enzyme dipeptidyl peptidase 4 (DPP 4).

The project examines the regulation of insulin secretion in relation to insulin resistance and development of type 2 diabetes. It studies subjects with diabetes or obesity, healthy subjects, diabetes models in mice, isolated islets and insulin−producing cell lines. Insulin and glucagon secretion and insulin sensitivity are studied by iv tests and hyperinsulinemic, euglycemic clamp technique. Islet mechanisms are explored by studying cellular signaling pathways. Current results show a hyperbolic relation between insulin sensitivity and insulin secretion both in humans and in mice and that failure to adequately increase insulin secretion in insulin resistance is due to altered muscarinic sensitivity in the islets, adverse effects induced by free fatty acids, leptin and ghrelin, and impaired beta cell translocation of GLUT−2 and transcription factors, such as PDX−1. Results also show that type 2 diabetes can be treated by glucagon−like peptide−1 (GLP−1) or by inhibiting the degradation of GLP−1 by using inhibitors of dipeptidyl peptidase−4 (DPP−4).

The project generates knowledge for the understanding of metabolic perturbations in obesity and for the development of type 2 diabetes. It also provides knowledge for targeting diabetes treatment.