Shuang Wang1, Qian-qian Sun, Bing Xiang, Xiu-Jun Li. 1. Department of Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China, 610041. wangs0211@hotmail.com
Abstract
PURPOSE: Autophagy induces pancreatic β cell death. The purpose of the present study was to examine the hypothesis that the extent of pancreatic autophagy is associated with aging and age-related diabetes. METHODS: Pancreatic tissue and blood samples were collected from Sprague Dawley rats receiving a normal diet at 2 (the young group), 6 (the adult group), 12 (the middle-age group) and 20-24 (the aged group) months of age. Body weight and fasting blood glucose, serum lipid levels and serum insulin levels were determined. Pancreatic cell structure and autophagy were determined using transmission electron microscopy of rats at 6, 12 and 24 months of age. Lamp2 and LC3b protein expression levels were determined by both immunohistochemistry and Western blot analyses, and islet cell apoptosis was assessed using the TUNEL assay. RESULTS: Fasting blood glucose, triglyceride and FFA levels increased significantly with age (p < 0.05). Compared with levels seen in two-month-old rats, insulin secretion of islet cells in vitro was significantly reduced at 6, 12, and 20 months of age (p < 0.05). Autophagosomes were only observed in islet cells of 24 month-old rats. Increased expression of the autophagic markers, Lamp2 and LC3b, was observed with age. A significant increase in apoptotic index was observed between young rats (two-months-old) and older rats (six-, 12- and 24-months-old), but no differences were observed between rats six, 12 and 24 months of age. CONCLUSION: Appearance of autophagosomes and increased Lamp2 and LC3b expression in pancreatic islet cells coincided with a significant decrease in insulin secretion and elevation of fasting blood glucose in aged rats.
PURPOSE: Autophagy induces pancreatic β cell death. The purpose of the present study was to examine the hypothesis that the extent of pancreatic autophagy is associated with aging and age-related diabetes. METHODS:Pancreatic tissue and blood samples were collected from Sprague Dawley rats receiving a normal diet at 2 (the young group), 6 (the adult group), 12 (the middle-age group) and 20-24 (the aged group) months of age. Body weight and fasting blood glucose, serum lipid levels and serum insulin levels were determined. Pancreatic cell structure and autophagy were determined using transmission electron microscopy of rats at 6, 12 and 24 months of age. Lamp2 and LC3b protein expression levels were determined by both immunohistochemistry and Western blot analyses, and islet cell apoptosis was assessed using the TUNEL assay. RESULTS: Fasting blood glucose, triglyceride and FFA levels increased significantly with age (p < 0.05). Compared with levels seen in two-month-old rats, insulin secretion of islet cells in vitro was significantly reduced at 6, 12, and 20 months of age (p < 0.05). Autophagosomes were only observed in islet cells of 24 month-old rats. Increased expression of the autophagic markers, Lamp2 and LC3b, was observed with age. A significant increase in apoptotic index was observed between young rats (two-months-old) and older rats (six-, 12- and 24-months-old), but no differences were observed between rats six, 12 and 24 months of age. CONCLUSION: Appearance of autophagosomes and increased Lamp2 and LC3b expression in pancreatic islet cells coincided with a significant decrease in insulin secretion and elevation of fasting blood glucose in aged rats.
Authors: Katrina J Binger; Martin Neukam; Sudhir Gopal Tattikota; Fatimunnisa Qadri; Dmytro Puchkov; Diana M Willmes; Sabrina Wurmsee; Sabrina Geisberger; Ralf Dechend; Klemens Raile; Thomas Kurth; Genevieve Nguyen; Matthew N Poy; Michele Solimena; Dominik N Muller; Andreas L Birkenfeld Journal: Proc Natl Acad Sci U S A Date: 2019-09-16 Impact factor: 11.205