Insulin induces monocytic CXCL8 secretion by the mitogenic signalling pathway.
Oral glucose uptake alters the function of immune cells and an elevation of systemic CXCL8 was described. Monocytes secrete high amounts of CXCL8 and therefore it was analyzed whether glucose or insulin upregulate monocytic CXCL8 release. Incubation of monocytes with insulin for 2h induced CXCL8 mRNA and secretion whereas glucose had no effect. Inhibition of the phosphatidylinositol 3-kinase by wortmannin or the mammalian target of rapamycin by rapamycin did not influence insulin-mediated CXCL8 induction. In contrast, blockage of the ERK-specific MAP kinase MEK with PD98059, that prevents phosphorylation of ERK1/ERK2, abrogated insulin-induced CXCL8 release in primary monocytes. To investigate the in vivo effect of oral glucose uptake, monocytes of healthy probands were isolated in the fasted state and 2h after glucose ingestion and CXCL8 mRNA and protein were increased in the latter. CXCL8 was also higher when determined in the cell lysate of leukocytes 2h after glucose uptake whereas plasma CXCL8 levels were significantly reduced. In summary, these data indicate that oral glucose uptake in insulin-sensitive adults is associated with elevated monocytic and reduced systemic CXCL8.
Wurm
Sylvia
S
Department of Internal Medicine I, Regensburg University Hospital, Franz Josef Strauss Allee 11, D-93042 Regensburg, Germany.
Neumeier
Markus
M
Weigert
Johanna
J
Wanninger
Josef
J
Gerl
Melanie
M
Gindner
Antonia
A
Schäffler
Andreas
A
Aslanidis
Charalampos
C
Schölmerich
Jürgen
J
Buechler
Christa
C
D000730:Androstadienes / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin; D055815:Young Adult
D000730:Androstadienes; D001786:Blood Glucose; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005419:Flavonoids; D005947:Glucose; D007328:Insulin; D016209:Interleukin-8; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin; C508606:CXCL8 protein, human; C546842:MTOR protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one