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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Bibliographic Details
Published in:Diabetic medicine Vol. 25; no. 2; pp. 157 - 164
Main Authors: 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.
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01.02.2008
Blackwell
Subjects:
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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Summary: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.
Bibliography: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.
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ISSN:0742-3071
1464-5491
1464-5491
DOI:10.1111/j.1464-5491.2007.02348.x