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Papers In Press, published online ahead of print December 1, 2004
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Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden 2300 RC
Corresponding Author: a.c.heijboer{at}lumc.nl
Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with hepatic insulin resistance. The purpose of the present study was to document the effects of 16 hours fasting in wildtype mice on insulin sensitivity in liver and skeletal muscle in relation to 1) tissue accumulation of triglycerides and 2) changes in mRNA expression of metabolically relevant genes. Sixteen hours of fasting did not show an effect on hepatic insulin sensitivity in terms of glucose production in the presence of increased hepatic triglyceride content (71+/-19 versus 12+/-7 µg/mg protein, p<0.01). In muscle, however, fasting resulted in increased insulin sensitivity with increased muscle glucose uptake (4.0+/-2.6 versus 1.3+/-0.3 % glucose uptake/ g tissue, p<0.01) without changes in muscle triglyceride content (25+/-7 versus 29+/-13 µg/mg protein, ns). In liver, fasting resulted in increased mRNA expression of genes promoting gluconeogenesis (PGC1 and PEPCK) and triglyceride synthesis (PPARgamma, DGAT1 and DGAT2), but in decreased mRNA expression of genes involved in glycogenolysis (GP) and fatty acid synthesis (SREBP1c, FAS and ACC1). In muscle, increased mRNA expression of genes promoting glucose uptake (PGC1 and GLUT-4), as well as lipogenesis (PPARgamma, FAS, ACC1, DGAT-1 and -2) and beta-oxidation (PPARalpha) was found. In conclusion, 16 hours fasting does not induce hepatic insulin resistance although it causes liver steatosis, whereas muscle insulin sensitivity increases without changes in muscle triglyceride content. Therefore, fasting induces differential changes in tissue-specific insulin sensitivity and liver and muscle TG content are unlikely to be involved in these changes.
Revised on November 26, 2004
Accepted on November 30, 2004
Sixteen hours fasting differentially affects hepatic and muscle insulin sensitivity in mice
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