Insulin infusion suppresses while glucose infusion induces Toll-like receptors and high-mobility group-B1 protein expression in mononuclear cells of type 1 diabetes patients

American Journal of Physiology - Endocrinology and Metabolism - Tập 304 Số 8 - Trang E810-E818 - 2013
Paresh Dandona1, Husam Ghanim1, Kelly Green1, Chang Ling Sia1, Sanaa Abuaysheh1, Nitesh Kuhadiya1, Manav Batra1, Sandeep Dhindsa1, Ajay Chaudhuri1
1Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York.

Tóm tắt

The purpose of this study was to determine whether an insulin infusion exerts an anti-inflammatory effect and whether the infusion of small amounts of glucose results in oxidative and inflammatory stress in patients with type 1 diabetes. Ten patients with type 1 diabetes were infused with either 2 U/h of insulin with 100 ml 5% dextrose/h to or just dextrose (100 ml/h) or physiological saline (100 ml/h) for 4 h after an overnight fast on three separate days. Blood samples were collected at 0, 2, 4, and 6 h. Insulin with glucose infusion led to the maintenance of euglycemia and a significant suppression of reactive oxygen species (ROS) generation, p47phox expression, Toll-like receptor (TLR)-4, TLR-2, TLR-1, CD14, high-mobility group-B1 (HMGB1), p38 mitogen-activated protein (MAP) kinase, c-Jun NH2-terminal kinase (JNK)-1, and platelet/endothelial cell adhesion molecule expression and a fall in serum concentrations of C-reactive protein, HMGB1, and rapid upon activation T cell expressed and secreted. Glucose infusion led to an increase in plasma glucose concentration from 115 (fasting) to 215 (at 4 and 6 h) mg/dl and to an increase in ROS generation, the expression of TLR-4, TLR-2, TLR-1, HMGB1, p38 MAP kinase, and JNK-1, and plasma concentrations of HMGB1. While insulin reduces indexes of oxidative and inflammatory stress in patients with type 1 diabetes, even small amounts of glucose (20 g over 4 h) induce oxidative and inflammatory stress. These effects are reflected in TLR, p38 MAP kinase, and HMGB1 expression. The induction of significant oxidative and inflammatory stress by small amounts of glucose in patients with type 1 diabetes may have important pathophysiological and therapeutic implications.

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Thông tin xuất bản

American Journal of Physiology - Endocrinology and Metabolism

Tập 304 Số 8

E810-E818

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