Gangliosides modulate insulin secretion by pancreatic beta cells under glucose stress
| Autor: | Hermann-Josef Gröne, Martina Volz, Silke Herzer, Richard Jennemann, Roger Sandhoff, Sylvia Kaden, Viola Nordström |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
endocrine system
medicine.medical_specialty Glucose uptake medicine.medical_treatment Mice Transgenic 030209 endocrinology & metabolism Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Gangliosides Insulin-Secreting Cells Internal medicine Diabetes mellitus medicine Animals Insulin Beta (finance) 030304 developmental biology 0303 health sciences biology Chemistry Pancreatic islets medicine.disease Mice Inbred C57BL Glucose Endocrinology medicine.anatomical_structure Membrane protein Apoptosis biology.protein GLUT2 lipids (amino acids peptides and proteins) |
| Zdroj: | Glycobiology. 30:722-734 |
| ISSN: | 1460-2423 |
| DOI: | 10.1093/glycob/cwaa022 |
| Popis: | 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 ultrastructure. Their insulin content, size and number were 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|