Abstract
Aims We investigated the changes of renal structure and its function in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in OLETF rats and explored the role of the INS/IRS-1/PI3-K/Akt signaling pathway. Methods OLETF rats were assigned into four groups on the basis of OGTT results and 24 h urinary microalbumin: NGT, IGT, DM, and DKD groups. The changes of renal structure and function and the corresponding pathological changes were observed. The absorption of albumin and the expression of megalin, cubilin, IRS-1, PI3-K, and Akt in NRK-52E cells were measured after being stimulated by different concentrations of insulin. Results In the IGT group, the index which reflects the function of renal tubule-like N-acetyl-β-glucosaminidase, neutrophil gelatinase-associated lipocalin, retinol-binding protein, and cystatin C was higher than those in the control group and the NGT group (P < 0.05). Significant renal structure damages, especially in renal tubules, were observed in the IGT group. In the presence of insulin at a high concentration, the IRS-1/PI3-K/Akt signaling pathway in renal tubular epithelial cells was inhibited, and the expression of megalin and cubilin was significantly downregulated which was accompanied by a minimum uptake of albumin. Conclusions In contrast to DKD, the renal structural damage and functional changes in the IGT stage, in which we propose the term “IGT kidney disease,” mainly manifest as renal tubular injury. Insulin resistance and compensatory hyperinsulinemia may be involved in its pathogenesis.
Highlights
With a rapid increase in the morbidity rate of diabetes mellitus (DM), diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease (ESRD) [1]
After 24 h, we found that the mRNA levels of megalin and cubilin were the highest in cells treated with 5 ng/mL insulin, which was different pSer IRS-1
OLETF rat, which manifests by obese, insulin resistance, spontaneous hyperglycemia, and proteinuria after 30 weeks, is an ideal animal model of DKD in human [11]
Summary
With a rapid increase in the morbidity rate of diabetes mellitus (DM), diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease (ESRD) [1]. We have found that a series of pathophysiological changes has occurred long before MAU in patients with type 2 diabetes leading to renal hypertrophy, abnormal blood pressure, and renal tubular dysfunction [4]. It is important to further dynamically study the alteration of kidney structure and function during the onset and progression of type 2 DM in different phases: normal glucose tolerance (NGT), IGT, DM, and DKD. Hyperinsulinemia impairs insulin activity and metabolic signaling pathways and affects the structure and function of the tissues and organs including the kidney. We dynamically studied the changes of the structure and function of renal tissue in different stages of type 2 DM (NGT, IGT, DM, and DKD stages) using OLETF rats. We studied the effects of different concentrations of the insulin and IRS-1/PI3-K/Akt pathway on albumin reabsorption in a rat proximal renal tubular epithelial cell line (NRK-52E)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
