Liver-Derived IGF-I is of Importance for Normal Carbohydrate and Lipid Metabolism
- Klara Sjögren12,
- Kristina Wallenius1,
- Jun-Li Liu5,
- Mohammad Bohlooly-Y2,
- Giovanni Pacini6,
- Lennart Svensson3,
- Jan Törnell2,
- Olle G.P. Isaksson1,
- Bo Ahrén4,
- John-Olov Jansson1 and
- Claes Ohlsson1
- 1Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital
- 2Department of Physiology, University of Göteborg, Göteborg
- 3Astrazeneca R&D, Mölndal
- 4Department of Medicine, Lund University, Malmö, Sweden
- 5Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland
- 6Institute of Systems Science and Biomedical Engineering, National Research Council, Padua, Italy
Abstract
IGF-I is important for postnatal body growth and exhibits insulin-like effects on carbohydrate metabolism. The function of liver-derived IGF-I is still not established, although we previously demonstrated that liver-derived IGF-I is not required for postnatal body growth. Mice whose IGF-I gene in the liver was inactivated at 24 days of age were used to investigate the long-term role of liver-derived IGF-I for carbohydrate and lipid metabolism. Serum levels of leptin in these mice were increased by >100% at 3 months of age, whereas the fat mass of the mice was decreased by 25% at 13 months of age. The mice became markedly hyperinsulinemic and yet normoglycemic, indicating an adequately compensated insulin resistance. Furthermore, they had increased serum levels of cholesterol. We conclude that liver-derived IGF-I is of importance for carbohydrate and lipid metabolism.
Footnotes
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Address correspondence and reprint requests to Olle Isaksson, MD, Department of Internal Medicine, Division of Endocrinology, RCEM, Sahlgrenska Hospital, SE-413 45 Göteborg, Sweden. E-mail: olle.isaksson{at}medic.gu.se.
Received for publication 19 October 2000 and accepted in revised form 13 April 2001.
AIR, acute first phase insulin secretion response; AUCins, area under the curve for insulin; DXA, dual X-ray absorptiometry; ES, embryonic stem; FFA, free fatty acid; GDI, global disposition index; GH, growth hormone; GHD, GH- deficient; IGF-BP, IGF-binding protein; IFN, interferon; KG, glucose tolerance index; LDLr, LDL receptor; PCR, polymerase chain reaction; rhIGF-I, recombinant human IGF-I; RPA, RNase protection assay; SG, glucose effectiveness; SI, insulin sensitivity index
