In 2014 the global prevalence of diabetes was estimated to be 9% among adults aged over 18 years and in 2012, an estimated 1.5 million deaths were directly caused by diabetes. The WHO projects that diabetes will be the 7th leading cause of death in 2030 and considers it as one of the major global health challenges. While there are several different forms of diabetes, type 2 is worldwide the most prevalent. Type 2 diabetes is the result of an interplay between insulin resistance which is often related to environmental factors, including decreased physical activity and obesity, and insulin deficiency as a results of betacell failure, often genetically determined.

Mitochondrial dysfunction plays a role in defective insulin secretion, in insulin resistance and in the pathogenesis of specific diabetic complications. Chronic subclinical inflammation links obesity to insulin resistance and drives vascular disease associated with diabetes. Fat tissue macrophages polarize to a more pro-inflammatory phenytype by switching metabolism from oxidative phosphorylation to glycolysis. This process seems enhanced under hyperglycemic conditions. Our research focuses on the delineation of the role of inflammation in obesity-associated insulin resistance and diabetes in general and on the role of mitochondrial function in particular.

Recent publications

  1. IL-37 protects against obesity-induced inflammation and insulin resistance. Ballak DB, van Diepen JA, Moschen AR, Jansen HJ, Hijmans A, Groenhof GJ, Leenders F, Bufler P, Boekschoten MV, Müller M, Kersten S, Li S, Kim S, Eini H, Lewis EC, Joosten LA, Tilg H, Netea MG, Tack CJ, Dinarello CA, Stienstra R. Nat Commun. 2014 Sep 3;5:4711.

  2. Mannose-binding lectin is required for the effective clearance of apoptotic cells by adipose tissue macrophages during obesity. Stienstra R, Dijk W, van Beek L, Jansen H, Heemskerk M, Houtkooper RH, Denis S, van Harmelen V, Willems van Dijk K, Tack CJ, Kersten S. Diabetes. 2014 Dec;63(12):4143-53.

  3. PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism. van Diepen JA, Jansen PA, Ballak DB, Hijmans A, Hooiveld GJ, Rommelaere S, Galland F, Naquet P, Rutjes FP, Mensink RP, Schrauwen P, Tack CJ, Netea MG, Kersten S, Schalkwijk J, Stienstra R. J Hepatol. 2014 Aug;61(2):366-72.

  4. MAP3K8 (TPL2/COT) affects obesity-induced adipose tissue inflammation without systemic effects in humans and in mice. Ballak DB, van Essen P, van Diepen JA, Jansen H, Hijmans A, Matsuguchi T, Sparrer H, Tack CJ, Netea MG, Joosten LA, Stienstra R. PLoS One. 2014 Feb 24;9(2):e89615.