Acute suppression of circulating sCD40L during hyperglycemia and euglycemic-hyperinsulinemia in healthy young males.
sCD40L is a proatherogenic cytokine, part of the tumor necrosis factor (TNF) superfamily and consistently associated with obesity, diabetes, and increased cardiovascular risk. Although the role of sCD40L in the onset/progression of cardiovascular complications of dysmetabolic diseases may be modulated by acute and/or chronic fluctuations of plasma insulin and glucose, very little has been done to clarify this interaction. The kinetic profile of sCD40L (and, in an exploratory manner, of several immunomodulatory factors), were measured during hyperglycemia and euglycemic-hyperinsulinemia in a group of 10 healthy young males (26.8 +/- 1.4 years). After an overnight fast, intravenous (iv) catheters were placed in antecubital veins of both arms for blood drawing and dextrose/insulin iv infusions. Procedures lasted 240 minutes including baseline (t = 0-60), hyperglycemia (t = 60-150; plasma glucose approximately 220 mg/dL via iv dextrose infusion), and euglycemic-hyperinsulinemia (t = 150-240; glucose infusion continued to clamp glycemic levels between 80 and 110 mg/dL; constant insulin infusion at 1.5 mU/kg/minute).Plasma for cytokine assays was sampled at 12 separate time-points. Plasma levels of sCD40L were significantly reduced (P < 0.01) during hyperglycemia and euglycemic-hyperinsulinemia, paralleling the kinetic profiles of free fatty acids and ketone bodies. This pattern was also observed in other immunomodulatory factors (notably cortisol and epidermal growth factor), while (interleukin [IL]-1alpha, IL-4, IL-6, IL-9, IL-10, TNF-alpha, Eotaxin) did not change significantly. Significant reductions of the proatherogenic cytokine sCD40L were observed during endogenous and exogenous hyperinsulinemia, independent of prevailing glucose concentration, in young healthy males. Our data suggest a mechanism by which correct insulin action may exert a beneficial protective role against inflammation, independent of its immediate glucose-lowering effect.
Oliver
Stacy R
SR
Institute for Clinical Translational Science Center, Department of Pediatrics, University of California-Irvine, 101 The City Drive, Orange, CA 92868, USA. soliver@uci.edu
Flores
Rebecca L
RL
Pontello
Andria M
AM
Rosa
Jaime S
JS
Zaldivar
Frank P
FP
Galassetti
Pietro R
PR
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood*; D016207:Cytokines / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000276:immunology*; D006946:Hyperinsulinism / Q000097:blood* / Q000276:immunology*; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male
D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D008055:Lipids; D023201:CD40 Ligand
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