Yao Wang1, Aiping Wang2, Hana Alkhalidy3, Jing Luo1, Elizabeth Moomaw1, Andrew P Neilson4, Dongmin Liu1. 1. Department of Human Nutrition, Foods, and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA, 24060, USA. 2. College of Life Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China. 3. Department of Nutrition and Food Technology, Jordan University of Science and Technology, Irbid, 22110, Jordan. 4. Plants for Human Health Institution, North Carolina State University, Kannapolis, NC, 28081, USA.
Abstract
SCOPE: Loss of functional β-cell mass is central for the deterioration of glycemic control in diabetes. The incretin hormone glucagon-like peptide-1 (GLP-1) plays a critical role in maintaining glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell mass. Agents that can directly promote GLP-1 secretion, thereby increasing insulin secretion and preserving β-cell mass, hold great potential for the treatment of T2D. METHODS AND RESULTS: GluTag L-cells, INS832/13 cells, and mouse ileum crypts and islets are cultured for examining the effects of flavone hispidulin on GLP-1 and insulin secretion. Mouse livers and isolated hepatocytes are used for gluconeogenesis. Streptozotocin-induced diabetic mice are treated with hispidulin (20 mg kg-1 day-1 , oral gavage) for 6 weeks to evaluate its anti-diabetic potential. Hispidulin stimulates GLP-1 secretion from the L-cell line, ileum crypts, and in vivo. This hispidulin action is mediated via activation of cyclic adenosine monophosphate/protein kinase A signaling. Hispidulin significantly improves glycemic control in diabetic mice, concomitant with improved insulin release, and β-cell survival. Additionally, hispidulin decreases hepatic pyruvate carboxylase expression in diabetic mice and suppresses gluconeogenesis in hepatocytes. Furthermore, hispidulin stimulates insulin secretion from β-cells. CONCLUSION: These findings suggest that Hispidulin may be a novel dual-action anti-diabetic compound via stimulating GLP-1 secretion and suppressing hepatic glucose production.
SCOPE: Loss of functional β-cell mass is central for the deterioration of glycemic control in diabetes. The incretin hormone glucagon-like peptide-1 (GLP-1) plays a critical role in maintaining glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell mass. Agents that can directly promote GLP-1 secretion, thereby increasing insulin secretion and preserving β-cell mass, hold great potential for the treatment of T2D. METHODS AND RESULTS: GluTag L-cells, INS832/13 cells, and mouse ileum crypts and islets are cultured for examining the effects of flavone hispidulin on GLP-1 and insulin secretion. Mouse livers and isolated hepatocytes are used for gluconeogenesis. Streptozotocin-induced diabeticmice are treated with hispidulin (20 mg kg-1 day-1 , oral gavage) for 6 weeks to evaluate its anti-diabetic potential. Hispidulin stimulates GLP-1 secretion from the L-cell line, ileum crypts, and in vivo. This hispidulin action is mediated via activation of cyclic adenosine monophosphate/protein kinase A signaling. Hispidulin significantly improves glycemic control in diabeticmice, concomitant with improved insulin release, and β-cell survival. Additionally, hispidulin decreases hepatic pyruvate carboxylase expression in diabeticmice and suppresses gluconeogenesis in hepatocytes. Furthermore, hispidulin stimulates insulin secretion from β-cells. CONCLUSION: These findings suggest that Hispidulin may be a novel dual-action anti-diabetic compound via stimulating GLP-1 secretion and suppressing hepatic glucose production.
Authors: Gregory Hostetler; Ken Riedl; Horacio Cardenas; Mayra Diosa-Toro; Daniel Arango; Steven Schwartz; Andrea I Doseff Journal: Mol Nutr Food Res Date: 2012-02-20 Impact factor: 5.914