Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans

Aims Type 2 diabetes is frequently associated with infectious complications. Swift activation of leucocytes is important for an adequate immune response. We determined the selective effects of hyperglycaemia and hyperinsulinaemia on lipopolysaccharide (LPS)‐induced proinflammatory gene expression a...

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Vydáno v:	Diabetic medicine Ročník 25; číslo 2; s. 157 - 164
Hlavní autoři:	Stegenga, M. E., Crabben, S. N. van der, Dessing, M. C., Pater, J. M., Van Den Pangaart, P. S., De Vos, A. F., Tanck, M. W., Roos, D., Sauerwein, H. P., Van Der Poll, T.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Oxford, UK Blackwell Publishing Ltd 01.02.2008 Blackwell
Témata:	Adult Biological and medical sciences cytokines Diabetes Mellitus, Type 2 - metabolism DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Endocrinopathies Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Gene Expression - genetics Glucose Clamp Technique Humans hyperglycaemia Hyperglycemia - metabolism hyperinsulinaemia Hyperinsulinism - metabolism I-kappa B Proteins Interleukin-1alpha - genetics Interleukin-1alpha - metabolism Male Medical sciences mRNA neutrophils Neutrophils - metabolism NF-KappaB Inhibitor alpha Original : Treatment RNA, Messenger - genetics RNA, Messenger - metabolism Vertebrates: anatomy and physiology, studies on body, several organs or systems Vertebrates: endocrinology Endocrinopathy Human Hyperinsulinemia Obesity Nutrition Acute Nutrition disorder Cytokine Granulocyte Metabolic diseases Biosynthesis Inflammation mRNA Gene expression Hyperglycemia Messenger RNA Production hyperglycaemia hyperinsulinaemia cytokines Neutrophil neutrophils Endocrinology Nutritional status
ISSN:	0742-3071, 1464-5491, 1464-5491
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Shrnutí:	Aims Type 2 diabetes is frequently associated with infectious complications. Swift activation of leucocytes is important for an adequate immune response. We determined the selective effects of hyperglycaemia and hyperinsulinaemia on lipopolysaccharide (LPS)‐induced proinflammatory gene expression and cytokine production in leucocytes and on neutrophil functions. Methods Six healthy humans were studied on four occasions for 6 h during: (i) lower insulinaemic euglycaemic clamp, (ii) lower insulinaemic hyperglycaemic clamp, (iii) hyperinsulinaemic euglycaemic clamp, and (iv) hyperinsulinaemic hyperglycaemic clamp. Target levels of plasma glucose were 12.0 mmol/l (hyperglycaemic clamps) or 5.0 mmol/l (euglycaemic clamps). Target plasma insulin levels were 400 pmol/l (hyperinsulinaemic clamps) or 100 pmol/l (lower insulinaemic clamps). Results Hyperglycaemia reduced LPS‐induced mRNA expression of nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor alpha (NFKBIA), interleukin‐1 alpha (IL1A) and chemokine (C‐C motif) ligand 3 (CCL3), whereas during hyperinsulinaemia enhanced mRNA levels occurred in six out of eight measured inflammation‐related genes, irrespective of plasma glucose levels. Combined hyperglycaemia and hyperinsulinaemia led to enhanced IL1A, interleukin‐1 beta (IL1B) and CCL3 mRNA levels upon LPS stimulation. Neither hyperglycaemia nor hyperinsulinaemia altered cytokine protein production, neutrophil migration, phagocytic capacity or oxidative burst activity. Conclusions These results suggest that short‐term hyperglycaemia and hyperinsulinaemia influence the expression of several inflammatory genes in an opposite direction, that the acute effects of hyperinsulinaemia on inflammatory mRNA levels may be stronger than those of hyperglycaemia, and that the effects of insulin, in particular, may be relevant in the concurrent presence of hyperglycaemia.
Bibliografie:	ark:/67375/WNG-DB0K1G35-D ArticleID:DME2348 istex:A74D6680B7C65ECF7171AFDAD352DD54B081683C Re‐use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0742-3071 1464-5491 1464-5491
DOI:	10.1111/j.1464-5491.2007.02348.x