title: Intramyocellular lipid levels are associated with peripheral, but not hepatic, insulin sensitivity in normal healthy subjects.
abstract: Increased levels of IMCL (intramyocellular lipid) have been shown to be associated with reduced steady-state glucose infusion rates during a hyperinsulinaemic-euglycaemic clamp (M-value). The aim of the present study was to explore how IMCL levels relate to the insulin-mediated suppression of endogenous glucose production [hepatic SI (insulin sensitivity)] and increase in glucose disposal (peripheral SI). In the present study, 11 healthy young adults (7 male, 4 female; aged 21-31 years) undertook, in random order, an hyperinsulinaemic-euglycaemic clamp combined with stable glucose isotope enrichment to measure peripheral and hepatic SI, a 1H-MRS (proton-magnetic resonance spectroscopy) scan to determine IMCL levels and a DXA (dual-energy X-ray absorptiometry) scan to assess body composition. 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 percentage of central fat mass (r=0.694, P=0.02), but were not related to whole-body FFM (fat-free mass; r=-0.472, P=0.1). IMCL levels correlated closely with the M-value (r=-0.727, P=0.01) and FFM-corrected peripheral SI (r=-0.675, P=0.02), but were not related to hepatic SI adjusted for body weight (r=0.08, P=0.8). The results of the present study suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral, but not hepatic, SI in normal populations. Given the close relationship 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.
authors.affiliation: University Department of Paediatrics, University of Cambridge, Cambridge, U.K. burak@cantab.net
authors.forename: Burak
authors.initials: B
authors.lastname: Salgin
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Sleigh
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Williams
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Jackson
authors.forename: Les J
authors.initials: LJ
authors.lastname: Bluck
authors.forename: Peter R
authors.initials: PR
authors.lastname: Murgatroyd
authors.forename: Sandy M
authors.initials: SM
authors.lastname: Humphreys
authors.forename: Sally
authors.initials: S
authors.lastname: Harding
authors.forename: T Adrian
authors.initials: TA
authors.lastname: Carpenter
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000096:biosynthesis*; D001823:Body Composition; D015992:Body Mass Index; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin