Effects of Growth Hormone on Glucose and Fat Metabolism in Human Subjects Jens O.L. Jørgensen, MD, DMSc a, * , Louise Møller, MD a , Morten Krag, MD a , Nils Billestrup, PhD b , Jens S. Christiansen, MD, DMSc a a Medical Department M (Endocrinology and Diabetes) and Institute of Experimental Clinical Research, Aarhus University Hospital, Norrebrogade 44, DK-800C, Aarhus, Denmark b Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark A link between the pituitary gland and glucose metabolism was originally observed by Houssay [1], who recorded increased sensitivity to insulin in hy- pophysectomized animals that was reversed by administration of anterior pituitary extracts. Forty years ago Rabinowitz and colleagues [2] showed that infusion of high-dose growth hormone (GH) into the brachial artery of healthy adults reduced forearm glucose uptake in both muscle and adi- pose tissue. This reduction is paralleled by increased muscular uptake and oxidation of free fatty acids (FFA). Moreover, GH completely blocked the effects of insulin when the two hormones were administered together. Despite years of subsequent research, the mechanisms whereby GH causes insulin resistance and stimulates lipolysis remain unclear. Several lines of ev- idence, however, suggest a close link between these two important effects of GH. This article focuses on in vivo data from tests performed in normal sub- jects and in patients who had abnormal GH status. The effect of GH on pro- tein metabolism is discussed elsewhere in this issue. Effects of growth hormone on glucose and fat metabolism Healthy subjects Using the human forearm as an experimental model, Rabinowitz and col- leagues [2] performed several classic studies on the effects of insulin and GH, * Corresponding author. E-mail address: jolj@dadlnet.dk (J.O.L. Jørgensen). 0889-8529/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ecl.2006.11.005 endo.theclinics.com Endocrinol Metab Clin N Am 36 (2007) 75–87