TY  - JOUR
AU  - Jennemann, Richard
AU  - Kaden, Sylvia
AU  - Volz, Martina
AU  - Nordström, Viola
AU  - Herzer, Silke
AU  - Sandhoff, Roger
AU  - Gröne, Hermann-Josef
TI  - Gangliosides Modulate Insulin Secretion by Pancreatic Beta-Cells under Glucose Stress.
JO  - Glycobiology
VL  - 30
IS  - 9
SN  - 1460-2423
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2020-00523
SP  - 722-734
PY  - 2020
N1  - 2020 Aug 20;30(9):722-734#EA:A411#LA:G130#
AB  - In pancreatic beta cells the entry of glucose and downstream signaling for insulin release is regulated by the glucose transporter 2 (Glut2) in rodents. Dysfunction of the insulin-signaling cascade may lead to diabetes mellitus. Gangliosides, sialic acid-containing glycosphingolipids (GSLs), have been reported to modulate the function of several membrane proteins. Murine islets express predominantly sialylated GSLs, particularly the simple gangliosides GM3 and GD3 having a potential modulatory role in Glut2 activity. Conditional, tamoxifen-inducible gene targeting in pancreatic islets has now shown that mice lacking the glucosylceramide synthase (Ugcg), which represents the rate-limiting enzyme in GSL-biosynthesis, displayed impaired glucose uptake and showed reduced insulin secretion. Consequently, mice with pancreatic GSL deficiency had higher blood glucose levels than respective controls after intraperitoneal glucose application. High fat diet feeding enhanced this effect. GSL-deficient islets did not show apoptosis or ER-stress and displayed a normal ultra-structure. Their insulin content, size and number was similar as in control islets. Isolated beta cells from GM3 synthase null mice unable to synthesize GM3 and GD3 also showed lower glucose uptake than respective control cells, corroborating the results obtained from the cell-specific model. We conclude that in particular the negatively charged gangliosides GM3 and GD3 of beta cells positively influence Glut2 function to adequately respond to high glucose loads.
LB  - PUB:(DE-HGF)16
C6  - pmid:32149357
DO  - DOI:10.1093/glycob/cwaa022
UR  - https://inrepo02.dkfz.de/record/153913
ER  -