TY  - JOUR
A1  - Salker, Madhuri S.
A1  - Singh, Yogesh
A1  - Zeng, Ni
A1  - Chen, Hong
A1  - Zhang, Shaqiu
A1  - Umbach, Anja T.
A1  - Fakhri, Hajar
A1  - Kohlhofer, Ursula
A1  - Quintanilla-Martinez, Leticia
A1  - Durairaj, Ruban R. Peter
A1  - Barros, Flavio S. V.
A1  - Vrljicak, Pavle
A1  - Ott, Sascha
A1  - Brucker, Sara Y.
A1  - Wallwiener, Diethelm
A1  - Madunić, Ivana Vrhovac
A1  - Breljak, Davorka
A1  - Sabolić, Ivan
A1  - Koepsell, Hermann
A1  - Brosens, Jan J.
A1  - Lang, Florian
T1  - Loss of endometrial sodium glucose cotransporter SGLT1 is detrimental to embryo survival and fetal growth in pregnancy
JF  - Scientific Reports
N2  - Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na\(^+\)-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (\(Slc5a1^{+/+}\)) but not in SGLT1 defcient (\(Slc5a1^{−/−}\)) mice. Endometrial glycogen content, litter size and weight of offspring at birth were signifcantly lower in \(Slc5a1^{−/−}\) mice. In humans, \(SLC5A1\) expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial \(SLC5A1\) expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our fndings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome.
KW  - biology
KW  - embryology
KW  - intrauterine growth
KW  - paediatric research
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173814
VL  - 7
ER  - 
TY  - JOUR
A1  - Otto, Christoph
A1  - Friedrich, Alexandra
A1  - Madunić, Ivana Vrhovac
A1  - Baumeier, Christian
A1  - Schwenk, Robert W.
A1  - Karaica, Dean
A1  - Germer, Christoph-Thomas
A1  - Schürmann, Annette
A1  - Sabolić, Ivan
A1  - Koepsell, Hermann, Hermann
T1  - Antidiabetic Effects of a Tripeptide That Decreases Abundance of Na\(^+\)-D-glucose Cotransporter SGLT1 in the Brush-Border Membrane of the Small Intestine
JF  - ACS Omega
N2  - 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) 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.
KW  - chemistry
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230654
N1  - Lizenz: https://pubs.acs.org/page/policy/authorchoice_termsofuse.html
VL  - 5
IS  - 45
ER  -