These data demonstrate that corticosteroid treatment increases chromium losses and that steroid-induced diabetes can be reversed by chromium supplementation. Follow-up, double-blind studies are needed to confirm these observations.

In search for an effective oral treatment for diabetes, we examined the capacity of glucose tolerance factor (GTF) extracted from yeast and administered orally to reduce hyperglycaemia in rat models exhibiting insulin deficiency. The cellular effect of GTF on the insulin signalling pathway was investigated in vitro. GTF (oral bolus), insulin (intraperitoneal) or their combination was administered to streptozotocindiabetic (STZ) or hyperglycaemic Cohen diabetic-sensitive (hyp-CDs) rats. Blood glucose (BG) and insulin levels were measured in the postprandial (PP) state and during an oral glucose tolerance test. Deoxy-glucose transport and insulin signal transduction were assessed in 3T3-L1 adipocytes and myoblasts incubated with the GTF. Low dose of insulin produced a 34 and 12·5 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. GTF induced a 33 and 17 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. When combined with insulin, a respective decrease (58 and 42 %) in BG levels was observed, suggesting a partially additive (hyp-CDs) or synergistic (STZ rats) effect of the GTF and insulin. GTF did not induce insulin secretion in hyp-CDs rats, yet it lowered their BG levels, proposing an effect on glucose clearance by peripheral tissues. GTF induced a dose-dependent increase in deoxy-glucose transport into myoblasts and fat cells similar to insulin, while the combined treatment resulted in augmented transport rate. GTF induced a dose-and timedependent phosphorylation of insulin receptor substrate 1, Akt and mitogen-activated protein kinase independent of insulin receptor phosphorylation. GTF exerts remarkable insulin-mimetic and insulin-potentiating effects, both in vivo and in vitro. It produces an insulin-like effect by acting on cellular signals downstream of the insulin receptor. These results demonstrate a potential source for a novel oral medication for diabetes.Key words: Diabetes: Yeast: Glucose tolerance factor: Glucose-lowering effect: Insulin signalling Drug treatment options for diabetes mellitus are many and diverse. Despite the use of intensive regimens combining several anti-diabetic drugs and insulin, glycaemic control declines over time in most diabetic patients, reflecting ongoing deterioration of b-cell function. As a consequence, much research has focused on identifying new therapeutic targets and pharmacological compounds that might correct impaired glucose homeostasis via novel pathways.

The effect of low energy laser (He-Ne) irradiation (LELI) on the process of angiogenesis in the infarcted rat heart and in the chick chorioallantoic membrane (CAM), as well as the proliferation of endothelial cells in tissue culture, was investigated. Formation of new blood vessels in the infarcted rat heart was monitored by counting proliferating endothelial cells in blood vessels. In the CAM model, defined areas were laser-irradiated or nonirradiated and blood vessel density was recorded in each site in the CAM at various time intervals. Laser irradiation caused a 3.1-fold significant increase in newly formed blood vessels 6 days post infarction, as compared with nonirradiated rats. In the CAM model, a slight inhibition of angiogenesis up to 2 days post irradiation and a significant enhancement of angiogenesis in the laser-irradiated foci as compared with control nonirradiated spots were evident. The LELI caused a 1.8-fold significant increase in the rate of proliferation in endothelial cells in culture over nonirradiated cells. It is concluded that LELI can promote the proliferation of endothelial cells in culture, which may partially explain the augmentation of angiogenesis in the CAM model and in the infarcted heart. These results may have clinical significance by offering therapeutic options to ameliorate angiogenesis in ischemic conditions.

l " desert plants l " steppic plants l " antidiabetic l " oxidative stress l " reactive oxygen species (ROS) l " hypoglycemic effect

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...