Thankamony, Ajay2; Capalbo, Donatella2; Marcovecchio, M Loredana2; Sleigh, Alison2; Jørgensen, Sine Wanda2; Hill, Nathan R2; Mooslehner, Katrin2; Yeo, Giles S H2; Bluck, Les2; Juul, Anders4; Vaag, Allan5; Dunger, David B2
1 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet5 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
CONTEXT: Low serum IGF-1 levels have been linked to increased risk for development of type 2 diabetes. However, the physiological role of IGF-1 in glucose metabolism is not well characterized. OBJECTIVE: Our objective was to explore glucose and lipid metabolism associated with variations in serum IGF-1 levels. DESIGN, SETTING AND PARTICIPANTS: IGF-1 levels were measured in healthy, nonobese male volunteers aged 18 to 50 years from a biobank (n = 275) to select 24 subjects (age 34.8 ± 8.9 years), 12 each in the lowest (low-IGF) and highest (high-IGF) quartiles of age-specific IGF-1 SD scores. Evaluations were undertaken after a 24-hour fast and included glucose and glycerol turnover rates using tracers, iv glucose tolerance test to estimate peripheral insulin sensitivity (IS) and acute insulin and C-peptide responses (indices of insulin secretion), magnetic resonance spectroscopy to measure intramyocellular lipids (IMCLs), calorimetry, and gene expression studies in a muscle biopsy. MAIN OUTCOME MEASURES: Acute insulin and C-peptide responses, IS, and glucose and glycerol rate of appearance (Ra) were evaluated. RESULTS: Fasting insulin and C-peptide levels and glucose Ra were reduced (all P < .05) in low-IGF compared with high-IGF subjects, indicating increased hepatic IS. Acute insulin and C-peptide responses were lower (both P < .05), but similar peripheral IS resulted in reduced insulin secretion adjusted for IS in low-IGF subjects (P = 0.044). Low-IGF subjects had higher overnight levels of free fatty acids (P = .028) and β-hydroxybutyrate (P = .014), increased accumulation of IMCLs in tibialis anterior muscle (P = .008), and a tendency for elevated fat oxidation rates (P = .058); however, glycerol Ra values were similar. Gene expression of the fatty acid metabolism pathway (P = .0014) was upregulated, whereas the GLUT1 gene was downregulated (P = .005) in the skeletal muscle in low-IGF subjects. CONCLUSIONS: These data suggest that serum IGF-1 levels could be an important marker of β-cell function and glucose as well as lipid metabolic responses during fasting.
Endocrinology, 2014, Vol 99, Issue 6, p. 2198-2207