Liver-Derived IGF-I is of Importance for Normal Carbohydrate and Lipid Metabolism

• Published in: Diabetes (New York, N.Y.) Vol. 50; no. 7; pp. 1539 - 1545
• Main Authors: SJÖGREN, Klara, WALLENIUS, Kristina, OHLSSON, Claes, LIU, Jun-Li, BOHLOOLY-Y, Mohammad, PACINI, Giovanni, SVENSSON, Lennart, TÖRNELL, Jan, ISAKSSON, Olle G. P, AHREN, Bo, JANSSON, John-Olov
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2001
• Subjects: Absorptiometry; Absorptiometry, Photon; Animals; Biological and medical sciences; blood; Blood Glucose; Blood Glucose - metabolism; Body Composition; Body Composition - genetics; Carbohydrates; chemistry; Chimera; Cholesterol; Cholesterol - blood; Diabetes; Diabetes research; Dietary Carbohydrates; Dietary Carbohydrates - metabolism; Dietary Fats; Dietary Fats - metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Silencing; genetics; Inbred C57BL; Insulin; Insulin - blood; Insulin Resistance; Insulin Resistance - genetics; Insulin-like growth factor 1; Insulin-Like Growth Factor I; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - physiology; Insulin-like growth factors; Lipid Metabolism; Lipids; Liver; Liver - chemistry; Liver. Bile. Biliary tracts; Male; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; Metabolism; Mice; Mice, Inbred C57BL; Photon; Physiological aspects; physiology; Vertebrates: digestive system; Sweden; Vertebrata; Mammalia; Targeting; Gene; Mouse; Digestive system; Liver; Rodentia; Lipids; Carbohydrate; Insulin like growth factor 1; Metabolism
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.50.7.1539

Liver-Derived IGF-I is of Importance for Normal Carbohydrate and Lipid Metabolism Klara Sjögren 1 2 , Kristina Wallenius 1 , Jun-Li Liu 5 , Mohammad Bohlooly-Y 2 , Giovanni Pacini 6 , Lennart Svensson 3 , Jan Törnell 2 , Olle G.P. Isaksson 1 , Bo Ahrén 4 , John-Olov Jansson 1 and Claes Ohlsson 1 1 Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital 2 Department of Physiology, University of Göteborg, Göteborg 3 Astrazeneca R&D, Mölndal 4 Department of Medicine, Lund University, Malmö, Sweden 5 Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 6 Institute 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 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; AUC ins , 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; K G , glucose tolerance index; LDLr, LDL receptor; PCR, polymerase chain reaction; rhIGF-I, recombinant human IGF-I; RPA, RNase protection assay; S G , glucose effectiveness; S I , insulin sensitivity index