Inhibition of Diabetic Nephropathy in Rats by an Oral Antidiabetic Material Extracted from Yeast

Abstract

Diabetic nephropathy is one of the major complications of diabetes. The glucose tolerance factor (GTF) is a dietary agent extracted from several natural sources; the richest among them is brewer's yeast. Extraction and purification of an active and stable GTF preparation from brewer's yeast previously was successful, and a remarkable decrease in plasma glucose and lipids from administration of GTF to animals with type 1 diabetes was demonstrated. The purpose of the present study was to examine whether GTF affects nephropathy in diabetic rats. The average urinary volume and protein excretion throughout the collection period in diabetic rats was 56.95 ؎ 2.2 ml/d and 5.42 ؎ 0.95 mg/d, respectively. These values were significantly (P < 0.001 versus baseline values) higher compared with healthy controls (average urine volume 15.12 ؎ 0.5 ml/d; average protein excretion 0.15 ؎ 0.08 mg/d). Treatment with GTF reduced average urine volume and protein excretion to 29.1 ؎ 1.94 ml/d (P < 0.01) and 1.55 ؎ 1.17 mg/d (P < 0.05), respectively. Kidney weight, which was elevated in diabetic rats, slightly decreased in diabetic animals that were treated with GTF, in association with reduction of lipid peroxidation levels in the renal cortex and the heart. Endothelial nitric oxide immunoreactivity in the renal cortex of both healthy and diabetic rats that were treated with GTF was remarkably lower than that found in renal cortex of untreated diabetic animals. This study demonstrates that yeast-derived material, GTF, can inhibit the development of nephropathy that is induced by diabetes.J Am Soc Nephrol 17: S127-S131, 2006. doi: 10.1681/ASN.2005121333 D iabetes is the leading cause of ESRD. Approximately 30% of patients with diabetes experience diabetic nephropathy, which gradually develops to final renal failure (1). Fifty percent of the patients who need dialysis treatment in Western countries have diabetes, and the number is constantly growing (2). Large-scale studies have established that hyperglycemia, the defining metabolic abnormality, increases the risk for diabetic renal disease (3,4).Although the complete mechanism of hyperglycemia that causes diabetic complications is not fully known, several biochemical pathways are involved in the pathogenesis, including increased formation of glucose-derived glycated end products, increased formation of reactive oxygen species (5-7), activation of aldose reductase pathway, and glucose-induced activation of protein kinase C. Reactive oxygen species exert their cytotoxic effects on membranes and cellular lipids, resulting in the formation of malondialdehyde (7,8). Oxidation of lipids in plasma lipoproteins and in cellular membranes is associated with the increased incidence of vascular disease in diabetes (9,10). Normally, protective mechanisms are present in the cell to prevent damage by free radicals (11). Enzymes such as superoxide dismutase, glutathione peroxidase, and catalase provide the detoxification steps for the oxidative products. It was shown that the activity of the antioxida...

Glucose Tolerance Factor – Insulin Mimetic and Potentiating Agent – A Source for a Novel Anti Diabetic Medication

“…We examined GTF effects in animal models for both types of diabetes, and found high and rapid anti diabetic, hypolipidemic and antioxidant activity. We also found a remarkable reduction in the complications of diabetes: nephropathy and retinopathy, by treating the diabetic animals with oral doses of GTF [81].…”

“…Fig. 9 presents the urine volume and Fig 10 presents urine protein of the different groups, indicating a significant reduction both in urine volume and in urine protein of diabetic rats treated with GTF (from Nakhoul et al, [81]). …”

“…Moreover, GTF is also stable to proteolytic enzymes. This finding enables an oral treatment with GTF, in contrast to insulin, which is a protein and has to be injected [49,80,81].…”

“…Different letters above bars indicate significant differences between groups. (From Nakhoul et al, [81].…”

“…The levels of lipid peroxidation products, TBARS, in the kidneys and hearts removed from healthy, diabetic, and diabetic rats treated with GTF are shown in figures 6 & 7 (From Nakhoul et al, [81] Figure 6 presents the level of lipid peroxidation products determined in the hearts of the various experimental groups. The value of lipid peroxides in untreated diabetic rats was significantly higher than the value detected for healthy animals.…”