Eur J Endocrinol
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DOI: 10.1530/EJE-09-0643
European Journal of Endocrinology, Vol 161, Issue 5, 715-722
Copyright © 2009 by European Society of Endocrinology
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CLINICAL STUDY

Role of insulin as a negative regulator of plasma endocannabinoid levels in obese and nonobese subjects

Vincenzo Di Marzo, An Verrijken1, Antti Hakkarainen2, Stefania Petrosino, Ilse Mertens1, Nina Lundbom2, Fabiana Piscitelli, Jukka Westerbacka3, Aino Soro-Paavonen3, Isabel Matias, Luc Van Gaal1 and Marja-Riitta Taskinen3

Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei, 34, Comprensorio Olivetti, 80078 Pozzuoli (NA), Italy1 Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, UA, B-2650 Antwerp, Belgium2 , Medical Imaging Center3 Department of Medicine, Helsinki University Hospital, Biomedicum, Haartmaninkatu 8, PO Box 700, 00029 Helsinki, Finland

(Correspondence should be addressed to V Di Marzo; Email: vdimarzo{at}icmib.na.cnr.it)

Objective: Endocannabinoids (ECs) control metabolism via cannabinoid receptors type 1 (CB1). Their plasma levels are elevated in overweight type 2 diabetes (T2D) and in obese patients, and decrease postprandially in normoweight individuals. We investigated in two different cohorts of nonobese or obese volunteers whether oral glucose in glucose tolerance tests (OGTT) or acute insulin infusion during euglycemic hyperinsulinemic clamp affect plasma EC levels.

Design and methods: OGTT was performed in ten obese hyperinsulinemic patients (body mass index (BMI)=35.8 kg/m2, fasting insulin=14.83 mU/l), and ten normoweight normoinsulinemic volunteers (BMI=21.9 kg/m2, fasting insulin=7.2 mU/l). Insulin clamp was performed in 19 mostly nonobese men (BMI=25.8 kg/m2) with varying degrees of liver fat and plasma triglycerides (TGs), with (n=7) or without T2D. Plasma levels of ECs (anandamide and 2-arachidonoylglycerol (2-AG)) were measured by liquid chromatography–mass spectrometry, before and 60 and 180 min after OGTT, and before and 240 and 480 min after insulin or saline infusion.

Results: Oral glucose load decreased anandamide plasma levels to an extent inversely correlated with BMI, waist circumference, subcutaneous fat, fasting insulin and total glucose, and insulin areas under the curve during the OGTT, and nonsignificantly in obese volunteers. Insulin infusion decreased anandamide levels to an extent that weakly, but significantly, correlated negatively with TGs, liver fat and fasting insulin, and positively with high density lipoprotein cholesterol. OGTT decreased 2-AG levels to a lower extent and in a way weakly inversely correlated with fasting insulin.

Conclusions: We suggest that insulin reduces EC levels in a way inversely related to anthropometric and metabolic predictors of insulin resistance and dyslipidemia.






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