Articles by Renate Haselgrübler in JoVE
An In Ovo Model for Testing Insulin-mimetic Compounds Renate Haselgrübler*1, Flora Stübl*1, Verena Stadlbauer1,2, Peter Lanzerstorfer1, Julian Weghuber1,2 1University of Applied Sciences Upper Austria, 2Austrian Competence Center for Feed and Food Quality, Safety and Innovation In this study, we describe an in-ovo system as a promising tool to test insulin-mimetic compounds in a living organism. The main advantages include adequate throughput rates and acceptable costs, which enable the identification of phytochemicals with insulin-mimetic properties.
Other articles by Renate Haselgrübler on PubMed
Identification of Novel Insulin Mimetic Drugs by Quantitative Total Internal Reflection Fluorescence (TIRF) Microscopy British Journal of Pharmacology. | Pubmed ID: 25039620 Insulin stimulates the transport of glucose in target tissues by triggering the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Resistance to insulin, the major abnormality in type 2 diabetes, results in a decreased GLUT4 translocation efficiency. Thus, special attention is being paid to search for compounds that are able to enhance this translocation process in the absence of insulin.
Biomolecular Characterization of Putative Antidiabetic Herbal Extracts PloS One. | Pubmed ID: 26820984 Induction of GLUT4 translocation in the absence of insulin is considered a key concept to decrease elevated blood glucose levels in diabetics. Due to the lack of pharmaceuticals that specifically increase the uptake of glucose from the blood circuit, application of natural compounds might be an alternative strategy. However, the effects and mechanisms of action remain unknown for many of those substances. For this study we investigated extracts prepared from seven different plants, which have been reported to exhibit anti-diabetic effects, for their GLUT4 translocation inducing properties. Quantitation of GLUT4 translocation was determined by total internal reflection fluorescence (TIRF) microscopy in insulin sensitive CHO-K1 cells and adipocytes. Two extracts prepared from purslane (Portulaca oleracea) and tindora (Coccinia grandis) were found to induce GLUT4 translocation, accompanied by an increase of intracellular glucose concentrations. Our results indicate that the PI3K pathway is mainly responsible for the respective translocation process. Atomic force microscopy was used to prove complete plasma membrane insertion. Furthermore, this approach suggested a compound mediated distribution of GLUT4 molecules in the plasma membrane similar to insulin stimulated conditions. Utilizing a fluorescent actin marker, TIRF measurements indicated an impact of purslane and tindora on actin remodeling as observed in insulin treated cells. Finally, in-ovo experiments suggested a significant reduction of blood glucose levels under tindora and purslane treated conditions in a living organism. In conclusion, this study confirms the anti-diabetic properties of tindora and purslane, which stimulate GLUT4 translocation in an insulin-like manner.
Gluc-HET, a Complementary Chick Embryo Model for the Characterization of Antidiabetic Compounds PloS One. | Pubmed ID: 28777818 Insulin resistance and β cell failure are the main causes of elevated blood glucose levels in Type 2 diabetes mellitus (T2DM), a complex and multifactorial metabolic disease. Several medications to treat or reduce the symptoms of T2DM are used, including the injection of insulin and the application of insulin sensitizing or glucose production reducing drugs. Furthermore, the use of phytochemicals has attracted increasing attention for the therapy and prevention of T2DM. In order to identify and characterize antidiabetic compounds, efficient test systems are required. Here we present a modified chick embryo model (hens egg test, HET), which has originally been developed to determine the potential irritancy of chemicals, as a versatile tool for the characterization of phytochemicals with antidiabetic properties. We termed this modified assay variation Gluc-HET. More precisely, we determined the influence of variations in the incubation time of the fertilized eggs and studied the effects of different buffer parameters, such as the temperature, composition and volume, used for drug application. In addition, we tested several putative antidiabetic plant extracts, which have been identified in an in-vitro primary screening procedure, for their effectiveness in reducing blood glucose levels in-ovo. Taken together, our Gluc-HET model has proven to be a reliable and manageable system for the characterization of antidiabetic compounds.