An Inhibition of Urinary Albumin Excretion by Protease Inhibitor in Streptozotocin-Diabetic Rats

Abstract

To evaluate the protecting effect of camostat mesylate, NN-dimethylcarba-moylmethyl-p-(p-guanidinobenzoyloxy)phenylacetate methanesulfonate, one of the synthetic trypsin inhibitors, on diabetic nephropathy, urinary albumin excretion was measured in streptozotocin-induced (50 mg/kg, i.p.) diabetic rats treated with oral camostat mesylate for 12 weeks. The rats were divided into three groups: (1) nondiabetic control rats; (2) diabetic rats, and (3) diabetic rats received rat chow containing 0.1% camostat mesylate (PI rats). After induction of diabetes, the ratio of kidney weight to body weight and urinary albumin excretion (UAE) were significantly increased. However, the ratio of kidney weight to body weight in PI rats was significantly lower than that in diabetic rats, and UAE in PI rats was also significantly lower than that in diabetic rats at 4, 8 and 12 weeks. Kidney tissue insulin-like growth factor I (IGF-I) contents were significantly reduced in diabetic rats, and there were no significant differences in kidney tissue IGF-I contents between diabetic and PI rats. These results suggest that camostat mesylate reduces the UAE probably through an inhibitory effect on initial diabetic renal hypertrophy and that camostat mesylate is available for diabetic nephropathy.

Evaluation of the components of insulin‐like growth factor (IGF)‐IGF binding protein (IGFBP) system in adolescents with type 1 diabetes and persistent microalbuminuria: relationship with increased urinary excretion of IGFBP‐3 18 kD N‐terminal fragment

“…In these conditions, IGFBP‐3 proteolysis results in the formation of IGFBP‐3 fragments that have decreased affinity for IGF‐I, therefore facilitating the hypoglycaemic activity of IGF‐I and countering the relative insulin deficiency. Interestingly, an increase of thrombin, a potential IGFBP‐3 protease (Booth et al ., 1996), has been reported in sera from patients with diabetes associated with MA (Leurs et al ., 1997), and in diabetic rats, treatment with a protease inhibitor reduced urinary albumin excretion (Ikeda & Hoshino, 1996). Whether IGFBP‐3 proteolyis, with production of low affinity IGFBP‐3 fragments, facilitates the development of diabetic nephropathy, remains to be investigated.…”

High Fructose‐Fed Rats: A Model of Glomerulosclerosis Involving The Renin‐Angiotensin System and Renal Gelatinases

“…In preliminary experiments, fructose‐fed and control animals were infused for 1 to 4 hours with angiotensin II (50 ng/ml/hr) using jugular catheters. Urinary albumin excretion rate, kidney and isolated glomeruli metalloprotease content 2 (quantitative normalized zymography), and renal histology were compared to baseline levels in animals submitted to acute angiotensin infusion either with or without angiotensin II type 1 receptor blockade (valsartan 40 mg/d in drinking water) during the 24 hr preceding the angiotensin infusion. Sacrifice was performed in all animals after 11 to 17 months of continuous diet in order to evaluate organomegaly, target tissue histology, and protein content.…”