TY - JOUR
T1 - Prolonged fasting induces peripheral insulin resistance, which is not ameliorated by high-dose salicylate
AU - van der Crabben, Saskia N.
AU - Allick, Gideon
AU - Ackermans, Mariette T.
AU - Endert, Erik
AU - Romijn, Johannes A.
AU - Sauerwein, Hans P.
PY - 2008
Y1 - 2008
N2 - CONTEXT: 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. DESIGN: Glucose and glutathione (GHS) metabolism was studied after 12 and 60 h of fasting on two occasions: with and without aspirin (6 g/d). SETTING: The study took place at the Academic Medical Center, Metabolic Research Unit. PARTICIPANTS: Six healthy lean men participated. INTERVENTION: Intervention included 60 h of fasting with or without aspirin ( approximately 6 g/d). MAIN OUTCOME MEASURE: 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. CONCLUSION: Prolonged fasting induces profound peripheral IR. In contrast to type 2 diabetes mellitus, high-dose salicylate does not affect fasting-induced peripheral IR
AB - CONTEXT: 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. DESIGN: Glucose and glutathione (GHS) metabolism was studied after 12 and 60 h of fasting on two occasions: with and without aspirin (6 g/d). SETTING: The study took place at the Academic Medical Center, Metabolic Research Unit. PARTICIPANTS: Six healthy lean men participated. INTERVENTION: Intervention included 60 h of fasting with or without aspirin ( approximately 6 g/d). MAIN OUTCOME MEASURE: 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. CONCLUSION: Prolonged fasting induces profound peripheral IR. In contrast to type 2 diabetes mellitus, high-dose salicylate does not affect fasting-induced peripheral IR
U2 - https://doi.org/10.1210/jc.2006-2491
DO - https://doi.org/10.1210/jc.2006-2491
M3 - Article
C2 - 18056775
SN - 0021-972X
VL - 93
SP - 638
EP - 641
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 2
ER -