TY - JOUR
T1 - Streptozotocin-induced β-cell damage, high fat diet, and metformin administration regulate Hes3 expression in the adult mouse brain
AU - German Mouse Clinic Consortium
AU - Nikolakopoulou, Polyxeni
AU - Chatzigeorgiou, Antonios
AU - Kourtzelis, Ioannis
AU - Toutouna, Louiza
AU - Masjkur, Jimmy
AU - Arps-Forker, Carina
AU - Poser, Steven W
AU - Rozman, Jan
AU - Rathkolb, Birgit
AU - Aguilar-Pimentel, Juan Antonio
AU - Wolf, Eckhard
AU - Klingenspor, Martin
AU - Ollert, Markus
AU - Schmidt-Weber, Carsten
AU - Fuchs, Helmut
AU - Gailus-Durner, Valerie
AU - Hrabe de Angelis, Martin
AU - Tsata, Vasiliki
AU - Monasor, Laura Sebastian
AU - Troullinaki, Maria
AU - Witt, Anke
AU - Anastasiou, Vivian
AU - Chrousos, George
AU - Yi, Chun-Xia
AU - García-Cáceres, Cristina
AU - Tschöp, Matthias H
AU - Bornstein, Stefan R
AU - Androutsellis-Theotokis, Andreas
PY - 2018/7/27
Y1 - 2018/7/27
N2 - Diabetes mellitus is a group of disorders characterized by prolonged high levels of circulating blood glucose. Type 1 diabetes is caused by decreased insulin production in the pancreas whereas type 2 diabetes may develop due to obesity and lack of exercise; it begins with insulin resistance whereby cells fail to respond properly to insulin and it may also progress to decreased insulin levels. The brain is an important target for insulin, and there is great interest in understanding how diabetes affects the brain. In addition to the direct effects of insulin on the brain, diabetes may also impact the brain through modulation of the inflammatory system. Here we investigate how perturbation of circulating insulin levels affects the expression of Hes3, a transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. Our data show that streptozotocin-induced β-cell damage, high fat diet, as well as metformin, a common type 2 diabetes medication, regulate Hes3 levels in the brain. This work suggests that Hes3 is a valuable biomarker helping to monitor the state of endogenous neural stem and progenitor cells in the context of diabetes mellitus.
AB - Diabetes mellitus is a group of disorders characterized by prolonged high levels of circulating blood glucose. Type 1 diabetes is caused by decreased insulin production in the pancreas whereas type 2 diabetes may develop due to obesity and lack of exercise; it begins with insulin resistance whereby cells fail to respond properly to insulin and it may also progress to decreased insulin levels. The brain is an important target for insulin, and there is great interest in understanding how diabetes affects the brain. In addition to the direct effects of insulin on the brain, diabetes may also impact the brain through modulation of the inflammatory system. Here we investigate how perturbation of circulating insulin levels affects the expression of Hes3, a transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. Our data show that streptozotocin-induced β-cell damage, high fat diet, as well as metformin, a common type 2 diabetes medication, regulate Hes3 levels in the brain. This work suggests that Hes3 is a valuable biomarker helping to monitor the state of endogenous neural stem and progenitor cells in the context of diabetes mellitus.
KW - Aging/metabolism
KW - Animals
KW - Basic Helix-Loop-Helix Transcription Factors/deficiency
KW - Brain/metabolism
KW - Diet, High-Fat
KW - Gene Expression Regulation/drug effects
KW - Insulin-Secreting Cells/drug effects
KW - Male
KW - Metformin/administration & dosage
KW - Mice, Inbred C57BL
KW - Nerve Tissue Proteins/deficiency
KW - Phenotype
KW - Streptozocin/toxicity
U2 - 10.1038/s41598-018-29434-2
DO - 10.1038/s41598-018-29434-2
M3 - Article
C2 - 30054579
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 11335
ER -