Endocrinology 2

Diabetes, endocrine pathofysiology and endocrine tumors

Principal investigators

Prof.Dr J.A. Romijn, Prof.Dr L.M. Havekes, Prof.Dr H. Pijl, Dr P.C.N. Rensen, Dr K. Willems van Dijk, Prof.Dr J.W. Smit

Aim and focus

The first objective of this research line is to investigate the underlying regulatory mechanisms involved in disturbances of glucose and lipid metabolism and their complications, including atherosclerosis, steatosis, and obesity. The results of these clinical and experimental studies are important for the development of new targets for the treatment of type 2 diabetes mellitus and atherosclerosis. Specifically, we evaluate the roles of the central nervous system, the gut-brain axis, and of tissue specific lipid metabolism in the modulation of insulin sensitivity of glucose metabolism.

The second objective is on pathophysiology and treatment of endocrine tumors (thyroid carcinoma, pituitary tumors). The strategy of this research line is to combine top-reference clinical care of these low-prevalent diseases with clinical and fundamental research. Research aims at the dissection of the molecular pathogenesis of these disorders and the development of novel diagnostic and therapeutic strategies. In addition, these disorders, that are usually accompanied by controlled changes in hormone systems, are also studied as models for endocrine regulation (e.g. effects of hypothyroidism on metabolism etc.

Position in international context

The research is performed within the context of a network within the LUMC (Endocrinology/AIG, Nephrology, Pathology, Cardiology, Surgery, Otolaryngology, Molecular Cell Biology) and outside the LUMC (Wageningen University, UMC Groningen, Netherlands Brain Institute, Columbia University).

Content / highlights / achievements

• The innervation of adipose tissue by parasympathetic nerves was elucidated. In addition, the function of this system was described.
• The effects of the gut-brain axis on insulin sensitivity were discovered.
• The modulation of fat mass by hepatic apolipoproteins was elucidated.
• A new method was described to study fatty acid and triglyceride kinetics in mice in vivo
• The long term consequences of protocollised medical, surgical and radiotherapeutical treatment of pituitary adenomas and thyroid carcinomas on morbidity and quality of life were described for very large, single center cohorts.
• The development of a designer single chain TSH molecule with superior biological activity

Future themes

• Elucidation of the tissue specific molecular mechanisms involved in the interaction between the central nervous system and insulin sensitivity
• Identification of the molecular mechanisms involved in the interaction between inflammatory pathways, fat metabolism and insulin resistance
• Development of a large cohort of subjects with obesity to study the pathophysiology of obesity and its complications.
• The consequences of long term follow up of protocollised surgical and radiotherapeutical treatment of nonfunctioning pituitary adenomas on morbidity and quality of life will be assessed.
• The development of molecular diagnostic and therapeutic anti TSH receptor strategies for thyroid carcinoma

Cohesion within the LUMC

This research is conducted through a collaboration between the Departments of Endocrinology, AIG, Molecular Cell Biology, TNO, Nephrology, and Clinical Epidemiology.

Key publications

van der Meer RW, Rijzewijk LJ, de Jong HW, Lamb HJ, Lubberink M, Romijn JA, Bax JJ, de Roos A, Kamp O, Paulus WJ, Heine RJ, Lammertsma AA, Smit JW, Diamant M. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation. 2009 Apr 21;119(15):2069-77.
IF 12.8

Hammer S, Snel M, Lamb HJ, Jazet IM, van der Meer RW, Pijl H, Meinders EA, Romijn JA, de Roos A, Smit JW. Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function. J Am Coll Cardiol. 2008 Sep 16;52(12):1006-12
IF 11.5

Rijzewijk LJ, van der Meer RW, Smit JW, Diamant M, Bax JJ, Hammer S, Romijn JA, de Roos A, Lamb HJ. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol. 2008 Nov 25;52(22):1793-9.
IF 11.5

van den Hoek AM, van Heijningen C, Schröder-van der Elst JP, Ouwens DM, Havekes LM, Romijn JA, Kalsbeek A, Pijl H. Intracerebroventricular administration of neuropeptide Y induces hepatic insulin resistance via sympathetic innervation. Diabetes. 2008 Sep;57(9):2304-10.
IF 9.02

de Haan W, de Vries-van der Weij J, van der Hoorn JW, Gautier T, van der Hoogt CC, Westerterp M, Romijn JA, Jukema JW, Havekes LM, Princen HM, Rensen PC. Torcetrapib does not reduce atherosclerosis beyond atorvastatin and induces more proinflammatory lesions than atorvastatin. Circulation. 2008 May 13;117(19):2515-22.
IF 12.8

Westerterp M, Berbée JF, Pires NM, van Mierlo GJ, Kleemann R, Romijn JA, Havekes LM, Rensen PC. Apolipoprotein C-I is crucially involved in lipopolysaccharide-induced atherosclerosis development in apolipoprotein E-knockout mice. Circulation. 2007 Nov 6;116(19):2173-81.
IF 12.8

Vidarsdottir S, Smeets PA, Eichelsheim DL, van Osch MJ, Viergever MA, Romijn JA, van der Grond J, Pijl H. Glucose ingestion fails to inhibit hypothalamic neuronal activity in patients with type 2 diabetes. Diabetes. 2007 Oct;56(10):2547-50.
IF 9.02