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Acute Suppression of Circulating sCD40L During Hyperglycemia and Euglycemic-Hyperinsulinemia in Healthy Young Males
  1. Stacy R. Oliver,
  2. Rebecca L. Flores,
  3. Andria M. Pontello,
  4. Jaime S. Rosa,
  5. Frank P. Zaldivar,
  6. Pietro R. Galassetti
  1. From the *Institute for Clinical Translational Science Center, Department of Pediatrics, University of California, Irvine, Orange; †Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA.
  1. This research was supported by NIH grants M01-RR00827-28 and JDRF grant #1-2006-76.
  2. Reprints: Stacy R. Oliver, MS, UCI ICTS, Bldg 25, 2nd Floor, 101 The City Drive, Orange, CA 92868. E-mail: soliver{at}uci.edu.

Abstract

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 ∼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]-1α, IL-4, IL-6, IL-9, IL-10, TNF-α, 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.

Key Words
  • sCD40L
  • cytokines
  • insulin
  • healthy
  • young males

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