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 - Neuhaus, Winfried
A1 - Burek, Malgorzata
A1 - Djuzenova, Cholpon C
A1 - Thal, Serge C
A1 - Koepsell, Hermann
A1 - Roewer, Norbert
A1 - Förster, Carola Y
T1 - Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the up-regulation of glucose uptake after subsequent reoxygenation in brain endothelial cells
N2 - During stroke the blood–brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non-competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7- fold after 6 h OGD, which was significantly reduced by 10 μM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907% after 6 h OGD and was still higher (210%) after the 20 h reoxygenation phase compared to normoxia. Ten micromolar MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells.
KW - Blut-Hirn-Schranke
KW - Schlaganfall
KW - Glucosetransportproteine
KW - NMDA-Antagonist
KW - NMDA-Rezeptor
KW - blood-brain barrier
KW - MK801
KW - NMDAR
KW - stroke
KW - glut1
KW - sglt1
Y1 - 2012
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67241
ER -
TY - JOUR
A1 - Gründemann, Dirk
A1 - Gorboulev, Valentin
A1 - Gambaryan, Stepan
A1 - Veyhl, Maike
A1 - Koepsell, Hermann
T1 - Drug excretion mediated by a new prototype of polyspecific transporter
N2 - CATIO~IC drugs of different types and structures (antihistaminics, antiarrhythmics, sedatives, opiates, cytostatics and antibiotics, for example) are excreted in mammals by epithelial cells of the renal proximal tubules and by hepatocytes in the liver1-4. In the proximal tubules, two functionally disparate transport systems are involved which are localized in the basolateral and luminal plasma membrane and are different from the previously identified neuronal monoamine transporters and A TP-dependent multidrug exporting proteins1-3,5-12. Here we report the isolation of a complementary DNA from rat kidney that encodes a 556-amino-acid membrane protein, OCT1, which has the functional characteristics of organic cation uptake over the basolateral membrane of renal proximal tubules and of organic cation uptake into hepatocytes. OCTl is not homologous to any other known protein and is found in kidney, liver and intestine. As OCTl translocates hydrophobic and hydrophilic organic cations of different structures, it is considered to be a new prolotype of polyspecific transporters that are important for drug elimination.
KW - Biologie
Y1 - 1994
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59327
ER -
TY - JOUR
A1 - Jaschke, Alexander
A1 - Chung, Bomee
A1 - Hesse, Deike
A1 - Kluge, Reinhart
A1 - Zahn, Claudia
A1 - Moser, Markus
A1 - Petzke, Klaus-Jürgen
A1 - Brigelius-Flohé, Regina
A1 - Puchkov, Dmytro
A1 - Koepsell, Hermann
A1 - Heeren, Joerg
A1 - Joost, Hans-Georg
A1 - Schürmann, Annette
T1 - The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium
JF - Human Molecular Genetics
N2 - The uptake and processing of dietary lipids by the small intestine is a multistep process that involves several steps including vesicular and protein transport. The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) controls the ARF-like 1 (ARL1)-mediated Golgi recruitment of GRIP domain proteins which in turn bind several Rab-GTPases. Here, we describe the essential role of ARFRP1 and its interaction with Rab2 in the assembly and lipidation of chylomicrons in the intestinal epithelium. Mice lacking Arfrp1 specifically in the intestine \((Arfrp1^{vil−/−})\) exhibit an early post-natal growth retardation with reduced plasma triacylglycerol and free fatty acid concentrations. \(Arfrp1^{vil−/−}\) enterocytes as well as Arfrp1 mRNA depleted Caco-2 cells absorbed fatty acids normally but secreted chylomicrons with a markedly reduced triacylglycerol content. In addition, the release of apolipoprotein A-I (ApoA-I) was dramatically decreased, and ApoA-I accumulated in the \(Arfrp1^{vil−/−}\) epithelium, where it predominantly co-localized with Rab2. The release of chylomicrons from Caco-2 was markedly reduced after the suppression of Rab2, ARL1 and Golgin-245. Thus, the GTPase ARFRP1 and its downstream proteins are required for the lipidation of chylomicrons and the assembly of ApoA-I to these particles in the Golgi of intestinal epithelial cells.
KW - ARF
Y1 - 2012
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125658
VL - 21
IS - 14
ER -
TY - JOUR
A1 - Koepsell, Hermann
T1 - Glucose transporters in brain in health and disease
JF - Pflügers Archiv - European Journal of Physiology
N2 - Energy demand of neurons in brain that is covered by glucose supply from the blood is ensured by glucose transporters incapillaries and brain cells. In brain, the facilitative diffusion glucose transporters GLUT1-6 and GLUT8, and the Na+-D-glucosecotransporters SGLT1 are expressed. The glucose transporters mediate uptake of D-glucose across the blood-brain barrier anddelivery of D-glucose to astrocytes and neurons. They are critically involved in regulatory adaptations to varying energy demandsin response to differing neuronal activities and glucose supply. In this review, a comprehensive overview about verified andproposed roles of cerebral glucose transporters during health and diseases is presented. Our current knowledge is mainly based onexperiments performed in rodents. First, the functional properties of human glucose transporters expressed in brain and theircerebral locations are described. Thereafter, proposed physiological functions of GLUT1, GLUT2, GLUT3, GLUT4, andSGLT1 for energy supply to neurons, glucose sensing, central regulation of glucohomeostasis, and feeding behavior are compiled, and their roles in learning and memory formation are discussed. In addition, diseases are described in which functionalchanges of cerebral glucose transporters are relevant. These are GLUT1 deficiency syndrome (GLUT1-SD), diabetes mellitus, Alzheimer’s disease (AD), stroke, and traumatic brain injury (TBI). GLUT1-SD is caused by defect mutations in GLUT1. Diabetes and AD are associated with changed expression of glucose transporters in brain, and transporter-related energy defi-ciency of neurons may contribute to pathogenesis of AD. Stroke and TBI are associated with changes of glucose transporter expression that influence clinical outcome
KW - glucosetransporter
KW - brain
KW - GLUT1
KW - GLUT2
KW - GLUT3
KW - GLUT4
KW - SGLT1
KW - diabetes
KW - Parkinson’s disease
KW - stroke
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232746
SN - 0031-6768
VL - 472
ER -
TY - JOUR
A1 - Koepsell, Hermann
T1 - Glucose transporters in the small intestine in health and disease
JF - Pflügers Archiv - European Journal of Physiology
N2 - Absorption of monosaccharides is mainly mediated by Na\(^+\)-d-glucose cotransporter SGLT1 and the facititative transporters GLUT2 and GLUT5. SGLT1 and GLUT2 are relevant for absorption of d-glucose and d-galactose while GLUT5 is relevant for d-fructose absorption. SGLT1 and GLUT5 are constantly localized in the brush border membrane (BBM) of enterocytes, whereas GLUT2 is localized in the basolateral membrane (BLM) or the BBM plus BLM at low and high luminal d-glucose concentrations, respectively. At high luminal d-glucose, the abundance SGLT1 in the BBM is increased. Hence, d-glucose absorption at low luminal glucose is mediated via SGLT1 in the BBM and GLUT2 in the BLM whereas high-capacity d-glucose absorption at high luminal glucose is mediated by SGLT1 plus GLUT2 in the BBM and GLUT2 in the BLM. The review describes functions and regulations of SGLT1, GLUT2, and GLUT5 in the small intestine including diurnal variations and carbohydrate-dependent regulations. Also, the roles of SGLT1 and GLUT2 for secretion of enterohormones are discussed. Furthermore, diseases are described that are caused by malfunctions of small intestinal monosaccharide transporters, such as glucose-galactose malabsorption, Fanconi syndrome, and fructose intolerance. Moreover, it is reported how diabetes, small intestinal inflammation, parental nutrition, bariatric surgery, and metformin treatment affect expression of monosaccharide transporters in the small intestine. Finally, food components that decrease d-glucose absorption and drugs in development that inhibit or downregulate SGLT1 in the small intestine are compiled. Models for regulations and combined functions of glucose transporters, and for interplay between d-fructose transport and metabolism, are discussed.
KW - glucose transporter
KW - small intestine
KW - regulation
KW - SGLT1
KW - GLUT2
KW - GLUT5
KW - glucose-galactose malabsorption
KW - fructose intolerance
KW - diabetes
KW - bariatric surgery
Y1 - 2020
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232552
SN - 0031-6768
VL - 472
ER -