title: Acute suppression of circulating sCD40L during hyperglycemia and euglycemic-hyperinsulinemia in healthy young males.
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 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.
authors.affiliation: Institute for Clinical Translational Science Center, Department of Pediatrics, University of California-Irvine, 101 The City Drive, Orange, CA 92868, USA. soliver@uci.edu
authors.forename: Stacy R
authors.initials: SR
authors.lastname: Oliver
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Flores
authors.forename: Andria M
authors.initials: AM
authors.lastname: Pontello
authors.forename: Jaime S
authors.initials: JS
authors.lastname: Rosa
authors.forename: Frank P
authors.initials: FP
authors.lastname: Zaldivar
authors.forename: Pietro R
authors.initials: PR
authors.lastname: Galassetti
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D008055:Lipids; D023201:CD40 Ligand
references.citation: Metabolism. 2006 Feb;55(2):237-42
references.pmid: 16423632
references.citation: Circulation. 2001 Nov 6;104(19):2266-8
references.pmid: 11696462
references.citation: Ann Pharmacother. 2004 Sep;38(9):1500-8
references.pmid: 15280513
references.citation: Ann Plast Surg. 2006 Apr;56(4):394-8; discussion 399-400
references.pmid: 16557070
references.citation: Am J Med Sci. 2005 Nov;330(5):227-32
references.pmid: 16284482
references.citation: Eur J Clin Invest. 2006 Jun;36(6):395-401
references.pmid: 16684123
references.citation: Platelets. 2006 Dec;17(8):577-85
references.pmid: 17127486
references.citation: Diabetes. 2005 Sep;54(9):2596-601
references.pmid: 16123347
references.citation: Diabetes. 2006 Dec;55(12):3299-308
references.pmid: 17130473
references.citation: Nature. 2006 Dec 14;444(7121):860-7
references.pmid: 17167474
references.citation: Circulation. 2002 Oct 15;106(16):2067-72
references.pmid: 12379575
references.citation: BJOG. 2006 Oct;113(10):1141-7
references.pmid: 16903845
references.citation: J Pediatr Endocrinol Metab. 2007 Dec;20(12):1293-305
references.pmid: 18341089
references.citation: Klin Med (Mosk). 2006;84(8):40-3
references.pmid: 17087190
references.citation: J Investig Med. 2008 Apr;56(4):701-13
references.pmid: 18382266
references.citation: J Hypertens. 2002 Jun;20(6):1215-21
references.pmid: 12023694
references.citation: Diabetes Care. 2002 Mar;25(3):537-41
references.pmid: 11874943
references.citation: Am J Physiol Endocrinol Metab. 2006 May;290(5):E833-9
references.pmid: 16332921
references.citation: J Am Coll Cardiol. 2006 Jan 17;47(2):391-7
references.pmid: 16412866
references.citation: Diab Vasc Dis Res. 2005 May;2(2):81-7
references.pmid: 16308911
references.citation: Endocrinology. 2007 Jan;148(1):346-53
references.pmid: 17008395
references.citation: Arch Med Res. 2005 Jul-Aug;36(4):376-81
references.pmid: 15950078
references.citation: J Immunol. 1997 Dec 1;159(11):5640-7
references.pmid: 9548507
references.citation: Nature. 2006 Dec 14;444(7121):875-80
references.pmid: 17167476
references.citation: Mediators Inflamm. 2006;2006(1):39062
references.pmid: 16864902
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2000 Apr;62(4):209-16
references.pmid: 10882184
references.citation: Am J Hypertens. 2003 May;16(5 Pt 1):331-6
references.pmid: 12745192
references.citation: Diabetologia. 2006 Jul;49(7):1670-6
references.pmid: 16752185
references.citation: Metabolism. 2006 May;55(5):691-5
references.pmid: 16631447
references.citation: Circulation. 2004 Jun 1;109(21):2524-8
references.pmid: 15136493
references.citation: J Clin Endocrinol Metab. 2003 Mar;88(3):1082-8
references.pmid: 12629088
references.citation: Endocr Rev. 2002 Oct;23(5):599-622
references.pmid: 12372842
references.citation: Diabetologia. 2004 Mar;47(3):537-540
references.pmid: 14963650
references.citation: Clin Chim Acta. 2004 Jan;339(1-2):85-90
references.pmid: 14687897
references.citation: Metabolism. 2006 Aug;55(8):1029-34
references.pmid: 16839837
references.citation: Clin Chem. 2007 Jul;53(7):1231-4
references.pmid: 17495016
references.citation: Thromb Haemost. 1998 May;79(5):1025-8
references.pmid: 9609241
references.citation: Nature. 1998 Feb 5;391(6667):591-4
references.pmid: 9468137
references.citation: N Engl J Med. 2003 Mar 20;348(12):1104-11
references.pmid: 12646667
references.citation: Thromb Haemost. 2003 Sep;90(3):377-84
references.pmid: 12958605
references.citation: Metabolism. 2006 Nov;55(11):1495-9
references.pmid: 17046552
references.citation: Diabetes. 2006 Jan;55(1):202-8
references.pmid: 16380494
references.citation: Clin Cardiol. 2007 Feb;30(2):86-91
references.pmid: 17326063
references.citation: J Clin Endocrinol Metab. 2001 Jan;86(1):450-3
references.pmid: 11232040
references.citation: Thromb Res. 2007;119(1):79-84
references.pmid: 16476470
references.citation: Circulation. 2005 Mar 22;111(11):1448-54
references.pmid: 15781756
references.citation: Am J Clin Nutr. 2006 Sep;84(3):505-12
references.pmid: 16960163
references.citation: Atherosclerosis. 2004 Oct;176(2):321-5
references.pmid: 15380455
references.citation: Int J Obes (Lond). 2006 Mar;30(3):400-18
references.pmid: 16302012
references.citation: Thromb Haemost. 1998 Dec;80(6):1008-14
references.pmid: 9869175
references.citation: Diabetes. 2005 Jan;54(1):85-91
references.pmid: 15616014
references.citation: Diabetologia. 1970 Feb;6(1):27-33
references.pmid: 5434734
references.citation: Atherosclerosis. 2006 Jul;187(1):18-25
references.pmid: 16360159
references.citation: Diabetes. 2006 Mar;55(3):774-9
references.pmid: 16505242
references.citation: Eur J Clin Invest. 2007 Aug;37(8):623-8
references.pmid: 17635572