Prolonged fasting induces peripheral insulin resistance, which is not ameliorated by high-dose salicylate.
BACKGROUND
Elevated plasma free fatty acids, excess reactive oxygen species, inflammation, and gluco-counterregulatory hormones induce insulin resistance (IR) through activation of Jun NH(2)-terminal kinase and nuclear factor-kappaB inhibitor kappaB kinase, which leads to hyperphosphorylation of the insulin receptor substrate type 1. Aspirin blocks nuclear factor-kappaB inhibitor kappaB kinase and improves IR in type 2 diabetes mellitus.


OBJECTIVE
We hypothesized that high-dose aspirin would also attenuate fasting-induced IR in healthy lean subjects.


METHODS
Glucose and glutathione (GHS) metabolism was studied after 12 and 60 h of fasting on two occasions: with and without aspirin (6 g/d).


METHODS
The study took place at the Academic Medical Center, Metabolic Research Unit.


METHODS
Six healthy lean men participated.


METHODS
Intervention included 60 h of fasting with or without aspirin ( approximately 6 g/d).


METHODS
Main outcome measures included glucose and GSH metabolism.


RESULTS
Fasting decreased insulin-mediated peripheral glucose uptake by 46% after 60 h (P = 0.03). Aspirin did not alter this effect of 60 h of fasting on insulin sensitivity (P = 0.03). GSH concentration decreased during fasting, but the fractional synthetic rate of GSH was unaffected either with or without aspirin. Fasting did not affect inflammatory parameters, although aspirin increased soluble TNF receptors I and II.


CONCLUSIONS
Prolonged fasting induces profound peripheral IR. In contrast to type 2 diabetes mellitus, high-dose salicylate does not affect fasting-induced peripheral IR.
Department of Endocrinology and Metabolism, Laboratory of Endocrinology, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherland. saskiananette@hotmail.com
Saskia N
SN
van der Crabben
Gideon
G
Allick
Mariette T
MT
Ackermans
Erik
E
Endert
Johannes A
JA
Romijn
Hans P
HP
Sauerwein
D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005215:Fasting / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D007328:Insulin; D005978:Glutathione; D005947:Glucose; D001241:Aspirin