ABSTRACT
Ronald Ma1, Keiji Isshiki2 and George L. King3 1Department of Medicine and Therapeutics, Prince Of Wales Hospital, Hong Kong, 2Department of Medicine, Shiga University of Medical Science, Seta, Otsu Shiga 520-2192, Japan, 3Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA
INTRODUCTION
The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) reported that the strict maintenance of euglycemia by intensive insulin treatment can delay the onset and slow the progression of diabetic nephropathy, respectively, in patients with type 1 and type 2 diabetes mellitus [1, 2]. These studies suggested that the adverse effects of hyperglycemia on metabolic pathways are the main causes of long-term complications in diabetes such as kidney disease. The importance of excessive glucose in the development of diabetic renal glomerular abnormalities is supported by the results of Heilig et al., who found that the overexpression of glucose transporter 1 (GLUT1) into glomerular mesangial cells enhanced the production of extracellular matrix components which may contribute to mesangial expansion [3]. Multiple biochemical mechanisms have been proposed to explain the adverse effects of hyperglycemia. Activation of diacylglycerol (DAG)-protein kinase C (PKC) pathway [4, 5], enhanced polyol pathway related with myo-inositol depletion [6], altered redox state [7], overproduction of advanced glycation end products [8], and enhanced growth factor and cytokine production [9, 10] have all been proposed as potential
cellular mechanisms by which hyperglycemia induces the chronic diabetic complications.
