Intramyocellular lipid levels are associated with peripheral but not hepatic insulin sensitivity in normal healthy subjects

Burak Salgin (1) , Alison J Sleigh , Rachel M Williams , Sarah J Jackson , Les J Bluck , Peter R Murgatroyd , Sandy M Humphreys , Sally Harding , Adrian Carpenter , David B. Dunger

1 University Department of Paediatrics

Aims: Increased levels of intra-myocellular lipid (IMCL) have been shown to be associated with reduced steady state glucose infusion rates during a hyperinsulinaemic euglycaemic clamp (M-value). Our aim was to explore how IMCL levels relate to the insulin-mediated suppression of endogenous glucose production (hepatic SI) and increase in glucose disposal (peripheral SI). Methods: 11 healthy young adults (7 male, 4 female) aged 21-31 years undertook, in random order, a hyperinsulinaemic euglycaemic clamp combined with stable glucose isotope enrichment to measure peripheral and hepatic SI, a 1H-magnetic resonance spectroscopy (1H-MRS) scan to determine IMCL levels and a dual energy X-ray absorptiometry (DXA) scan to assess body composition. Results: IMCL levels (range: 3.2-10.7) were associated with whole-body fat mass (r=0.787, p=0.004), fat mass corrected for height (r=0.822, p=0.002) and % central fat mass (r=0.694, p=0.02), but were not related to whole-body fat-free mass (FFM) (r=-0.472, p=0.1). IMCL levels correlated closely with the M-value (r=-0.727, p=0.01), FFM-corrected peripheral SI (r=-0.644, p=0.03), but were not related to hepatic SI adjusted for body weight (r=0.147, p=0.7). Conclusion: Our data suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral but not hepatic SI in normal populations. Given the close relation of IMCL levels to whole-body and central abdominal fat mass, relative increases in the flux of lipids from adipose tissue to the intramyocellular compartment may be an integral part of the mechanisms underlying reductions in SI.

Mots clés: Medicine

Burak Salgin, Alison J Sleigh, Rachel M Williams, Sarah J Jackson, Les J Bluck, et al.. Intramyocellular lipid levels are associated with peripheral but not hepatic insulin sensitivity in normal healthy subjects. Clinical Science, 2009, 117 (3), pp.111-118. ⟨10.1042/CS20080563⟩. ⟨hal-00496947⟩