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

作者：Michiel E. Stegenga, Saskia N. van der Crabben, Mark C. Dessing, Jennie M. Pater, Petra S. van den Pangaart, Alex F. de Vos, Michael W.T. Tanck, Dirk Roos, H. P. Sauerwein, Tom van der Poll · 发表于：Diabetic Medicine · 年份：2008 · DOI：10.1111/j.1464-5491.2007.02348.x · 被引用次数：118 · 研究领域：Hyperglycemia and glycemic control in critically ill and hospitalized patients、Adipokines, Inflammation, and Metabolic Diseases、Diabetes and associated disorders

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 kappa 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 oxidat...