Low circulating levels of IGF-1 in healthy adults are associated with reduced β-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting

J Clin Endocrinol Metab. 2014 Jun;99(6):2198-207. doi: 10.1210/jc.2013-4542. Epub 2014 Mar 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Fasting / metabolism*
  • Glucose / metabolism
  • Health
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Secreting Cells / physiology*
  • Lipid Metabolism*
  • Lipids / analysis
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / chemistry
  • Muscle Fibers, Skeletal / metabolism*
  • Young Adult

Substances

  • Lipids
  • Insulin-Like Growth Factor I
  • Glucose