The effect of high-dose sodium salicylate on chronically elevated plasma nonesterified fatty acid-induced insulin resistance and β-cell dysfunction in overweight and obese nondiabetic men.
Prolonged elevation of plasma nonesterified fatty acids (NEFA) induces insulin resistance and impairs pancreatic β-cell adaptation to insulin resistance. Studies in rodents suggest that inflammation may play a role in this "lipotoxicity." We studied the effects of sodium salicylate, an anti-inflammatory agent, on lipid-induced alterations in β-cell function and insulin sensitivity in six overweight and obese nondiabetic men. Each subject underwent four separate studies, 4-6 wk apart, in random order: 1) SAL, 1-wk placebo followed by intravenous (iv) infusion of saline for 48 h; 2) IH, 1-wk placebo followed by iv infusion of intralipid plus heparin for 48 h to raise plasma NEFA approximately twofold; 3) IH + SS, 1-wk sodium salicylate (4.5 g/day) followed by 48-h IH infusion; and 4) SS, 1-wk oral sodium salicylate followed by 48-h saline infusion. After 48-h saline or lipid infusion, insulin secretion and sensitivity were assessed by hyperglycemic clamp and euglycemic hyperinsulinemic clamp, respectively, in sequential order. Insulin sensitivity was reduced by lipid infusion (IH = 67% of SAL) and was not improved by salicylate (IH + SS = 56% of SAL). Lipid infusion also reduced the disposition index (P < 0.05), which was not prevented by sodium salicylate. Salicylate reduced insulin clearance. These data suggest that oral sodium salicylate at this dose impairs insulin clearance but does not ameliorate lipid-induced insulin resistance and β-cell dysfunction in overweight and obese nondiabetic men.
Xiao
Changting
C
Departments of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada.
Giacca
Adria
A
Lewis
Gary F
GF
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology; D019540:Area Under Curve; D002096:C-Peptide / Q000378:metabolism; D004655:Emulsions / Q000008:administration & dosage / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000096:biosynthesis / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism*; D010743:Phospholipids / Q000008:administration & dosage / Q000494:pharmacology; D012980:Sodium Salicylate / Q000494:pharmacology*; D013024:Soybean Oil / Q000008:administration & dosage / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D002096:C-Peptide; D004655:Emulsions; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010743:Phospholipids; D014280:Triglycerides; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil; D006493:Heparin; D005947:Glucose; D012980:Sodium Salicylate