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Incretin and Islet Biology

Department of Clinical Sciences Lund
Head: Bo Ahrén

Group members

Bo Ahrén, PI, MD, Professor

Bilal Omar, Research scientist
Siri Malmgren, Postdoc
Wathik Alsalim, MD, PhD student
Linda Ahlkvist, PhD student
Johan Farngren, MD
Kristina Andersson, BMA
Bertil Nilsson, Research Nurse

Introduction

The goal of the project is to understand the role of incretin hormones in islet physiology and islet dysfunction in T2D with special focus on GLP-1, to guide the further development of incretin-based treatment strategies. This is achieved by an interdisciplinary approach, involving subjects with T2D and obesity, healthy volunteers, experimental animals and isolated islets.

The goals of the project are to understand:

  1. the contribution of GLP-1 to islet adaptation to insulin resistance and development of T2D
  2. how GLP-1 secretion is regulated in vivo, to develop a novel therapy of T2D based on stimulation of GLP-1 secretion together with DPP-4 inhibition
  3. the hybrid combination of GLP-1 plus glucagon in the treatment of obesity and T2D
  4. the physiological “non-classical” (non-incretin) islet actions of GLP-1.

The project will have impact on diabetes research in general since it establishes the physiology of incretin hormones in relation to islet function with special emphases on pathophysiology (mainly the key islet dysfunction). The project will also have impact on diabetes care since it will guide the future development of incretin-based therapy. 

Highlights

  1. B Omar, B Andersen, J Hald, K Raun, E Nishimura, B Ahrén: Fibroblast growth factor 21 (FGF21) and glucagon-like peptide 1 contribute to diabetes resistance in glucagon recepor deficient mice. Diabetes 63:101-110 (2014)
  2. O Lindgren, G Pacini, A Tura, JJ Holst, CF Deacon, B Ahrén: Incretin effect after oral amino acid ingestion in humans. J Clin Endocrinol Metab 100:1172-1176 (2015)
  3. S Malmgren, B Ahrén: DPP-4 inhibition contributes to the prevention of hypoglycaemia through a GIP-glucagon counterregulatory axis in mice. Diabetologia 58:1091-1099 (2015)
  4. W Alsalim, A Tura, G Pacini, B Omar, R Bizzotto, A Mari, B Ahrén: Mixed meal ingesation diminishes glucose excursion in comparison with glucose ingestion via several adaptive mechanisms in people with and without type 2 diabetes. Diabet Obes Metab 18:24-33 (2016)
  5. J Farngren, M Persson, B Ahrén: Effect of the GLP-1 receptor agonist lixisenatide on counter-regulatory responses to hypoglycemia in subjects with insulin-treated type 2 diabetes Diabetes Care 39:242-249 (2016)

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00