Yumi Imai1,2, Ryan S Cousins3, Siming Liu1,2, Brian M Phelps3, Joseph A Promes1,2. 1. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa. 2. Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa. 3. Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, Virginia.
Abstract
Obesity is the major contributing factor for the increased prevalence of type 2 diabetes (T2D) in recent years. Sustained positive influx of lipids is considered to be a precipitating factor for beta cell dysfunction and serves as a connection between obesity and T2D. Importantly, fatty acids (FA), a key building block of lipids, are a double-edged sword for beta cells. FA acutely increase glucose-stimulated insulin secretion through cell-surface receptor and intracellular pathways. However, chronic exposure to FA, combined with elevated glucose, impair the viability and function of beta cells in vitro and in animal models of obesity (glucolipotoxicity), providing an experimental basis for the propensity of beta cell demise under obesity in humans. To better understand the two-sided relationship between lipids and beta cells, we present a current view of acute and chronic handling of lipids by beta cells and implications for beta cell function and health. We also discuss an emerging role for lipid droplets (LD) in the dynamic regulation of lipid metabolism in beta cells and insulin secretion, along with a potential role for LD under nutritional stress in beta cells, and incorporate recent advancement in the field of lipid droplet biology.
pan class="Disease">Obesity is the major contributing factor for the increased prevalence of pan class="Disease">type 2 diabetes (T2D) in recent years. Sustained positive influx of lipids is considered to be a precipitating factor for beta cell dysfunction and serves as a connection between obesity and T2D. Importantly, fatty acids (FA), a key building block of lipids, are a double-edged sword for beta cells. FA acutely increase glucose-stimulated insulin secretion through cell-surface receptor and intracellular pathways. However, chronic exposure to FA, combined with elevated glucose, impair the viability and function of beta cells in vitro and in animal models of obesity (glucolipotoxicity), providing an experimental basis for the propensity of beta cell demise under obesity in humans. To better understand the two-sided relationship between lipids and beta cells, we present a current view of acute and chronic handling of lipids by beta cells and implications for beta cell function and health. We also discuss an emerging role for lipid droplets (LD) in the dynamic regulation of lipid metabolism in beta cells and insulin secretion, along with a potential role for LD under nutritional stress in beta cells, and incorporate recent advancement in the field of lipid droplet biology.
Authors: Alice Marmugi; Julia Parnis; Xi Chen; LeAnne Carmichael; Julie Hardy; Naila Mannan; Piero Marchetti; Lorenzo Piemonti; Domenico Bosco; Paul Johnson; James A M Shapiro; Céline Cruciani-Guglielmacci; Christophe Magnan; Mark Ibberson; Bernard Thorens; Héctor H Valdivia; Guy A Rutter; Isabelle Leclerc Journal: Diabetes Date: 2016-01-28 Impact factor: 9.461
Authors: Camille Attané; Marie-Line Peyot; Roxane Lussier; Pegah Poursharifi; Shangang Zhao; Dongwei Zhang; Johane Morin; Marco Pineda; Shupei Wang; Olivier Dumortier; Neil B Ruderman; Grant A Mitchell; Brigitte Simons; S R Murthy Madiraju; Erik Joly; Marc Prentki Journal: Diabetologia Date: 2016-09-27 Impact factor: 10.122
Authors: Akansha Mishra; Siming Liu; Joseph Promes; Mikako Harata; William Sivitz; Brian Fink; Gourav Bhardwaj; Brian T O'Neill; Chen Kang; Rajan Sah; Stefan Strack; Samuel Stephens; Timothy King; Laura Jackson; Andrew S Greenberg; Frederick Anokye-Danso; Rexford S Ahima; James Ankrum; Yumi Imai Journal: JCI Insight Date: 2021-05-10
Authors: Siming Liu; Joseph A Promes; Mikako Harata; Akansha Mishra; Samuel B Stephens; Eric B Taylor; Anthony J Burand; William I Sivitz; Brian D Fink; James A Ankrum; Yumi Imai Journal: Diabetes Date: 2020-04-20 Impact factor: 9.461
Authors: Barbara J Olack; Michael Alexander; Carol J Swanson; Julie Kilburn; Nicole Corrales; Antonio Flores; Jennifer Heng; Jayagowri Arulmoli; Keiko Omori; Peter J Chlebeck; Laura Zitur; Mayra Salgado; Jonathan R T Lakey; Joyce C Niland Journal: Cell Transplant Date: 2020 Jan-Dec Impact factor: 4.064
Authors: Anna B Osipovich; Jennifer S Stancill; Jean-Philippe Cartailler; Karrie D Dudek; Mark A Magnuson Journal: Diabetes Date: 2020-04-24 Impact factor: 9.337