Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na\(^+\)-D-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-230654
- In enterocytes, protein RS1 (RSC1A1) mediates an increase of glucose absorption after ingestion of glucose-rich food via upregulation of Na+-D-glucose cotransporter SGLT1 in the brush-border membrane (BBM). Whereas RS1 decelerates the exocytotic pathway of vesicles containing SGLT1 at low glucose levels between meals, RS1-mediated deceleration is relieved after ingestion of glucose-rich food. Regulation of SGLT1 is mediated by RS1 domain RS1-Reg, in which Gln-Ser-Pro (QSP) is effective. In contrast to QSP and RS1-Reg, Gln-Glu-Pro (QEP) andIn enterocytes, protein RS1 (RSC1A1) mediates an increase of glucose absorption after ingestion of glucose-rich food via upregulation of Na+-D-glucose cotransporter SGLT1 in the brush-border membrane (BBM). Whereas RS1 decelerates the exocytotic pathway of vesicles containing SGLT1 at low glucose levels between meals, RS1-mediated deceleration is relieved after ingestion of glucose-rich food. Regulation of SGLT1 is mediated by RS1 domain RS1-Reg, in which Gln-Ser-Pro (QSP) is effective. In contrast to QSP and RS1-Reg, Gln-Glu-Pro (QEP) and RS1-Reg with a serine to glutamate exchange in the QSP motif downregulate the abundance of SGLT1 in the BBM at high intracellular glucose concentrations by about 50%. We investigated whether oral application of QEP improves diabetes in db/db mice and affects the induction of diabetes in New Zealand obese (NZO) mice under glucolipotoxic conditions. After 6-day administration of drinking water containing 5 mM QEP to db/db mice, fasting glucose was decreased, increase of blood glucose in the oral glucose tolerance test was blunted, and insulin sensitivity was increased. When QEP was added for several days to a high fat/high carbohydrate diet that induced diabetes in NZO mice, the increase of random plasma glucose was prevented, accompanied by lower plasma insulin levels. QEP is considered a lead compound for development of new antidiabetic drugs with more rapid cellular uptake. In contrast to SGLT1 inhibitors, QEP-based drugs may be applied in combination with insulin for the treatment of type 1 and type 2 diabetes, decreasing the required insulin amount, and thereby may reduce the risk of hypoglycemia.…
Autor(en): | Christoph Otto, Alexandra Friedrich, Ivana Vrhovac Madunić, Christian Baumeier, Robert W. Schwenk, Dean Karaica, Christoph-Thomas Germer, Annette Schürmann, Ivan Sabolić, Hermann Koepsell, Hermann |
---|---|
URN: | urn:nbn:de:bvb:20-opus-230654 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) |
Medizinische Fakultät / Institut für Anatomie und Zellbiologie | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | ACS Omega |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 5 |
Heft / Ausgabe: | 45 |
Seitenangabe: | 29127-29139 |
Originalveröffentlichung / Quelle: | ACS Omega 2020, 5, 29127−29139. DOI:10.1021/acsomega.0c03844 |
DOI: | https://doi.org/10.1021/acsomega.0c03844 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | chemistry |
Datum der Freischaltung: | 22.04.2021 |
Sammlungen: | Open-Access-Publikationsfonds / Förderzeitraum 2020 |
Anmerkungen: | Lizenz: https://pubs.acs.org/page/policy/authorchoice_termsofuse.html |