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Short‐term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated
Author(s) -
Johnson N. A.,
Stannard S. R.,
Rowlands D. S.,
Chapman P. G.,
Thompson C. H.,
Sachinwalla T.,
Thompson M. W.
Publication year - 2006
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2006.01952.x
Subject(s) - medicine , insulin sensitivity , endocrinology , term (time) , insulin resistance , diabetes mellitus , physics , quantum mechanics
Aims Metabolic responses to manipulation of the plasma free fatty acid (FFA) concentration were assessed in six healthy men via cross‐over design to determine whether FFAs independently influence insulin sensitivity. Methods Intramyocellular lipid (IMCL) was measured by proton magnetic resonance spectroscopy and insulin sensitivity via frequently sampled intravenous glucose tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC) diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion. Results Vastus lateralis IMCL was significantly elevated in LC (13.3 ± 1.1 × 10 −3 ) and LC + NA (13.5 ± 1.1 × 10 −3 ) ( P < 0.01 for both), but was not different between conditions ( P > 0.05). Plasma FFAs were raised in LC (0.79 ± 0.08 mmol/l) and LC + NA (0.80 ± 0.11 mmol/l) ( P < 0.01 for both) and were significantly reduced by NA ingestion prior to (0.36 ± 0.05 mmol/l, P < 0.01) and during IVGTT ( P < 0.05) in LC + NA. Despite marked differences in plasma FFA availability, insulin sensitivity and glucose tolerance were not different between LC and LC + NA ( P > 0.05 for both). Conclusions Plasma FFAs appear to exert no immediate effect on insulin sensitivity/glucose tolerance independent of their action on intracellular lipid moieties. Further research is required to elucidate the duration of FFA suppression required to restore insulin sensitivity following lipid‐induced insulin resistance.