TY  - JOUR
A1  - Jurowich, Christian Ferdinand
A1  - Otto, Christoph
A1  - Rikkala, Prashanth Reddy
A1  - Wagner, Nicole
A1  - Vrhovac, Ivana
A1  - Sabolić, Ivan
A1  - Germer, Christoph-Thomas
A1  - Koepsell, Hermann
T1  - Ileal interposition in rats with experimental type 2 like diabetes improves glycemic control independently of glucose absorption
JF  - Journal of Diabetes Research
N2  - Bariatric operations in obese patients with type 2 diabetes often improve diabetes before weight loss is observed. In patients mainly Roux-en-Y-gastric bypass with partial stomach resection is performed. Duodenojejunal bypass (DJB) and ileal interposition (IIP) are employed in animal experiments. Due to increased glucose exposition of L-cells located in distal ileum, all bariatric surgery procedures lead to higher secretion of antidiabetic glucagon like peptide-1 (GLP-1) after glucose gavage. After DJB also downregulation of Na\(^{+}\)-D-glucose cotransporter SGLT1 was observed. This suggested a direct contribution of decreased glucose absorption to the antidiabetic effect of bariatric surgery. To investigate whether glucose absorption is also decreased after IIP, we induced diabetes with decreased glucose tolerance and insulin sensitivity in male rats and investigated effects of IIP on diabetes and SGLT1. After IIP, we observed weight-independent improvement of glucose tolerance, increased insulin sensitivity, and increased plasma GLP-1 after glucose gavage. The interposed ileum was increased in diameter and showed increased length of villi, hyperplasia of the epithelial layer, and increased number of L-cells. The amount of SGLT1-mediated glucose uptake in interposed ileum was increased 2-fold reaching the same level as in jejunum. Thus, improvement of glycemic control by bariatric surgery does not require decreased glucose absorption.
KW  - glucagon like peptide-1
KW  - food intake
KW  - body weight
KW  - cotransporter SGLT1
KW  - bariatric surgery
KW  - biliopancreatic diversion
KW  - intestinal glucose
KW  - gut hormones
KW  - duodenal jejunal bypass
KW  - Y-gastric bypass
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149166
VL  - 2015
IS  - 490365
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  -