Effects of C-peptide on glomerular and renal size and renal function in diabetic rats (original) (raw)

2001, Kidney International

Effects of C-peptide on glomerular and renal size and renal glomerular hyperfiltration, which can be observed soon function in diabetic rats. after diabetes onset [1, 2]. Glomerular hyperfiltration is Background. Strict glycemic control and antihypertensive often accompanied by a loss of renal functional reserve treatment may decrease but not eliminate the risk of progres-(RFR) [3]. After some years, microalbuminuria (30 to sive nephropathy in diabetic patients. C-peptide has been shown to exert beneficial effects on complications, including 300 mg/day) may occur [4] as well as morphological incipient nephropathy, in type 1 diabetes. changes such as thickening of the glomerular basement Methods. Renal effects of 14 days of intravenous infusion membrane and mesangial expansion [5]. The albumin of C-peptide or NaCl (placebo) were studied in three groups leakage may subsequently become aggravated and overt of rats: one nondiabetic NaCl-treated (normal, N ϭ 7), one nephropathy with albuminuria (Ͼ300 mg/day) may destreptozotocin diabetic NaCl-treated (D-placebo, N ϭ 7), and one streptozotocin diabetic C-peptide-treated group (D-C-p, velop, usually 10 to 20 years after the onset of diabetes. N ϭ 7). Metabolic data and albuminuria were measured in meta-At this time, hypertension becomes more common. Nebolic cages every fourth day. After 14 days, the glomerular filtraphrotic syndrome may occur, and glomerular filtration tion rate (GFR) was measured by inulin clearance and available rate declines. The most important therapeutic measures renal functional reserve (RFR) by glycine infusion, whereupon one kidney was perfusion fixed for morphological studies. undertaken to avoid, or retard, the progress of nephropa-Results. Glucose levels were 36.7 Ϯ 1.3 and 34.0 Ϯ 1.7 mmol/L thy aim to improve glycemic control [6-8] and normalize in the D-placebo and D-C-p groups, respectively. The D-plablood pressure [9-11]. Angiotensin-converting enzyme cebo group presented a 32% (P Ͻ 0.001) larger glomerular inhibitors have proven effective in the latter respect and volume than the D-C-p group. The D-placebo group also prealso are beneficial in normotensive type 1 diabetic pasented a significantly larger renal weight than the normal group in contrast to the D-C-p group. Urinary albumin excretion tients [11, 12]. However, despite these efforts, progresincreased in the D-placebo group in contrast to the other sive nephropathy is seen often, in some cases leading to groups. GFR was 1.72 Ϯ 0.12 mL/min (normal), 3.73 Ϯ 0.19 mL/ end-stage renal disease. Thus, additional factors are min (D-placebo, P Ͻ 0.001 vs. normal) and 2.16 Ϯ 0.16 mL/ likely involved in this process. A lack of C-peptide may min (D-C-p, nonsignificant vs. normal). Available RFR was 93 Ϯ 25% (normal), 10 Ϯ 4% (D-placebo, P Ͻ 0.05 vs. normal) be one such factor. and 57 Ϯ 13% (D-C-p, nonsignificant vs. normal) of basal GFR. Earlier, C-peptide was considered to be without any Conclusions. Physiological doses of homologous C-peptide biological activity [13, 14] other than to facilitate the prevent the development of glomerular hypertrophy, albuminfolding of the proinsulin molecule in the proper way to uria, and glomerular hyperfiltration in rats with experimentally permit formation of disulfide bridges between the ␣and induced diabetes.