1365-P: Intermittent Fasting Modifies Pancreatic Glucosensor Mechanism In Diabetic Mice

• Published in: Diabetes (New York, N.Y.) Vol. 71; no. Supplement_1
• Main Authors: VILCHES-FLORES, ALONSO, PADILLA-ROMERO, YAZMIN
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2022
• Subjects: Beta cells; Body weight loss; Diabetes; Diabetes mellitus; Enzymatic activity; Fasting; Gene expression; Glucokinase; Glucose; Glucose tolerance; Glucose transporter; High fat diet; Immunohistochemistry; Insulin; Insulin secretion; Localization; Pancreas; Transcription factors
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db22-1365-P

Background: A specific feature in type-2 diabetes is beta-cell dysfunction, associated to reduction in glucose-stimulated insulin secretion. This function is high-regulated by the glucose sensor mechanism, conformed by GLUT2 and glucokinase, and their expresión is decreased in type-2 diabetes. Intermittent fasting is a recent option in diet control, with alternate cycles of fasting and feeding. In this study we evaluated intermittent fasting in diabetic mice, and its long-term effect in pancreatic GLUT2 and glucokinase expression. Methods: C57BL6 mice were fed with high fat diet for eight weeks, and then intermittent fasting cycles among four weeks. Weight, total caloric intake, fasting and glucose tolerance were determinated. Changes in insulin and glucokinase expression were evatualed by immunohistochemistry assays. Glucose-stimulated insulin secretion, and PDX1, insulin, GLUT2 and glucokinase mRNAs were analyzed in isolated islets. Results: Intermittent fasting caused weight loss, reduction in total caloric intake decrease and enhanced glucose tolerance. In diabetic mice, glucose-stimulated insulin secretion was restored after intermittent fasting, without significant changes in hormone content. Treated groups with fasting increased gene expression of PDX1, insulin and GLUT2, but decreased glucokinase mRNA and localization in beta-cells, but enhanced alpha-cell possitive presence. Conclusion: Intermittent fasting modifies glucosensor mechanism in pancreatic islets from diabetic mice, through GLUT2, PDX1 and insulin expression, but glucokinase. On future studies we will determine changes glucokinase enzymatic activity, and another transcription factors involved in these effects. Disclosure A.Vilches-flores: None. Y.Padilla-romero: None. Funding UNAM PAPIIT IN225819