IGF-1 Induction by Acylated Steryl β-Glucosides Found in a Pre-Germinated Brown Rice Diet Reduces Oxidative Stress in Streptozotocin-Induced Diabetes

Abstract

BackgroundThe pathology of diabetic neuropathy involves oxidative stress on pancreatic β-cells, and is related to decreased levels of Insulin-like growth factor 1 (IGF-1). Acylated steryl β-glucoside (PR-ASG) found in pre-germiated brown rice is a bioactive substance exhibiting properties that enhance activity of homocysteine-thiolactonase (HTase), reducing oxidative stress in diabetic neuropathy. The biological importance of PR-ASG in pancreatic β-cells remains unknown.Here we examined the effects of PR-ASG on IGF-1 and glucose metabolism in β-cells exposed to oxidative stress.Methodology/Principal FindingsIn the present study, a pre-germinated brown rice (PR)-diet was tested in streptozotocin (STZ)-induced diabetic rats. Compared with diabetic rats fed control diets, the PR-diet fed rats showed an improvement of serum metabolic and neurophysiological parameters. In addition, IGF-1 levels were found to be increased in the serum, liver, and pancreas of diabetic rats fed the PR-diet. The increased IGF-1 level in the pancreas led us to hypothesize that PR-ASG is protective for islet β-cells against the extensive injury of advanced or severe diabetes. Thus we examined PR-ASG to determine whether it showed anti-apoptotic, pro-proliferative effects on the insulin-secreting β-cells line, INS-1; and additionally, whether PR-ASG stimulated IGF-1 autocrine secretion/IGF-1-dependent glucose metabolism. We have demonstrated for the first time that PR-ASG increases IGF-1 production and secretion from pancreatic β-cells.Conclusion/SignificanceThese findings suggest that PR-ASG may affect pancreatic β-cells through the activation of an IGF-1-dependent mechanism in the diabetic condition. Thus, intake of pre-germinated brown rice may have a beneficial effect in the treatment of diabetes, in particular diabetic neuropathy.

Nutrigenomic effects of germinated brown rice and its bioactives on hepatic gluconeogenic genes in type 2 diabetic rats and HEPG2 cells

“…GBR also improved adiponectin insufficiency, suggesting that it could lessen inflammatory changes and improve insulin insufficiency. Similar findings , like the data from the current study, in diabetic rats have largely corroborated findings of antihyperglycemic effects of GBR. Findings in human studies have also mirrored those of chemically induced diabetes, suggesting that GBR does indeed produce similar antihyperglycemic effects in humans as in animal studies.…”

Antidiabetic Properties of Germinated Brown Rice: A Systematic Review

“…ASG has been shown to regenerate sodium potassium adenosine triphosphatase and homocysteine thiolactonase enzymes with potential to reverse diabetic neuropathy and oxidative changes on biomolecules [50]. It has also been reported to improve the overall metabolic condition in diabetes as a result of induction of insulin-like growth factor-1 and reduced oxidative stress [58], which is a problem in type 2 diabetes. Several improvements in metabolic indices have also been directly linked to certain bioactive compounds in GBR [48, 54, 55, 57].…”

“…Metabolic improvements due to GBR that may be beneficial in the management of type 2 diabetes include better glycemic control [13, 44–48, 51, 52, 55, 56], correction of dyslipidemia [46, 49, 51, 52, 54, 55, 57], amelioration of oxidative stress [40, 58], reduced type 1 tissue plasminogen activator inhibitor (PAI-1) [45, 56], and increased sodium potassium adenosine triphosphatase and homocysteine thiolactonase activities [50, 58]. Of the studies reported to date, only one has shown that GBR does not improve any metabolic indices in type 2 diabetes [44].…”

“…In addition, Usuki et al [58] showed that reduction of oxidative stress by GBR may be due to its acylated steryl glycoside (ASG) content. Using a diabetic rat model (fasting blood glucose of ≥400 mg/dL following injection of 65 mg/kg streptozotocin dissolved in 100 mmol/L sodium citrate buffer, pH 4.5), they demonstrated that ASG could increase activities of sodium potassium adenosine triphosphatase and homocysteine thiolactonase enzymes, whose impairment is linked to oxidative stress in diabetic neuropathy and cardiovascular complications.…”

Cell-based assays for IGF-I bioactivity measurement: overview, limitations and current trends

“…Recently, the water-soluble tetrazolium salt WST-8 was used to demonstrate a functional role of IGF-IGFBP-vibronectin complex in the proliferation of porcine enamel organ-derived epithelial cells (Shinohara et al, 2012) and to examine the effects of acylated steryl b-glucoside on IGF-I and glucose metabolism in b-cells exposed to oxidative stress (Usuki et al, 2011), while INT was used to determine the effect of IGF-I on Glioma (Safdie et al, 2012). The MTT assay has been recently employed to evaluate the effects of IGF-I, basic-fibroblast growth factor and neuregulin on the survival and morphogenesis on mammary epithelial and cancer cells (Accornero et al, 2012) and to measure the effect of IGF-I on the apoptosis of CHO cells (Piroozmand et al, 2013), while the MTS assay has found application in several assays to determine the effect of IGF-I on cell viability and proliferation (Hou et al, 2011;Sivaramakrishnan et al, 2013;Volkova et al, 2014;Wojtalla et al, 2012).…”