Min Jeong Kwon1, Yong Jae Lee2, Hye Sook Jung3, Hyun Mi Shin3, Tae Nyun Kim4, Soon Hee Lee4, Byoung Doo Rhee4, Mi-Kyung Kim5, Jeong Hyun Park6. 1. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea. 2. CKD Research Institute, Yongin, Gyeonggi-do, Republic of Korea. 3. Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea. 4. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea. 5. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea. Electronic address: kmkdoc@paik.ac.kr. 6. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Inje University, Busan, Republic of Korea; Paik Institute for Clinical Research, Molecular Therapy Lab, Inje University, Busan, Republic of Korea. Electronic address: pjhdoc@chol.com.
Abstract
AIMS: The direct effects of thiazolidinediones (TZDs) on pancreatic beta cells have been controversial. The aim of this study was to find out whether a novel TZD, lobeglitazone, has beneficial effects on pancreatic beta cells and db/db mice compared to those of other TZDs. METHODS: INS-1 cells were incubated at a high-glucose concentration with various concentrations of troglitazone, rosiglitazone, pioglitazone, and lobeglitazone. Apoptosis and proliferation of beta cells, markers for ER stress and glucose-stimulated insulin secretion (GSIS) were assessed. In addition, C57BL/6 db/db mice were treated with pioglitazone or lobeglitazone for 4 weeks, and metabolic parameters and the configuration of pancreatic islets were also examined. RESULTS: Lobeglitazone and other TZDs decreased INS-1 cell apoptosis in high-glucose conditions. Lobeglitazone and other TZDs significantly decreased hyperglycemia-induced increases in ER stress markers and increased GSIS. Metabolic parameters showed greater improvement in db/db mice treated with pioglitazone and lobeglitazone than in control mice. Islet size, cell proliferation, and beta cell mass were increased, and collagen surrounding the islets was decreased in treated mice. CONCLUSIONS: Lobeglitazone showed beneficial effects on beta cell survival and function against hyperglycemia. The prosurvival and profunction effects of lobeglitazone were comparable to those of other TZDs.
AIMS: The direct effects of thiazolidinediones (TZDs) on pancreatic beta cells have been controversial. The aim of this study was to find out whether a novel TZD, lobeglitazone, has beneficial effects on pancreatic beta cells and db/db mice compared to those of other TZDs. METHODS: INS-1 cells were incubated at a high-glucose concentration with various concentrations of troglitazone, rosiglitazone, pioglitazone, and lobeglitazone. Apoptosis and proliferation of beta cells, markers for ER stress and glucose-stimulated insulin secretion (GSIS) were assessed. In addition, C57BL/6 db/db mice were treated with pioglitazone or lobeglitazone for 4 weeks, and metabolic parameters and the configuration of pancreatic islets were also examined. RESULTS:Lobeglitazone and other TZDs decreased INS-1 cell apoptosis in high-glucose conditions. Lobeglitazone and other TZDs significantly decreased hyperglycemia-induced increases in ER stress markers and increased GSIS. Metabolic parameters showed greater improvement in db/db mice treated with pioglitazone and lobeglitazone than in control mice. Islet size, cell proliferation, and beta cell mass were increased, and collagen surrounding the islets was decreased in treated mice. CONCLUSIONS:Lobeglitazone showed beneficial effects on beta cell survival and function against hyperglycemia. The prosurvival and profunction effects of lobeglitazone were comparable to those of other TZDs.
Authors: Soree Ryang; Sang Soo Kim; Ji Cheol Bae; Ji Min Han; Su Kyoung Kwon; Young Il Kim; Il Seong Nam-Goong; Eun Sook Kim; Mi-Kyung Kim; Chang Won Lee; Soyeon Yoo; Gwanpyo Koh; Min Jeong Kwon; Jeong Hyun Park; In Joo Kim Journal: Diabetes Obes Metab Date: 2022-06-09 Impact factor: 6.408