@article{DjelićBorozanDimitrijevićSrećkovićetal.2022,
  author    = {Djelić, Ninoslav and Borozan, Sunčica and Dimitrijević-Srećković, Vesna and Pajović, Nevena and Mirilović, Milorad and Stopper, Helga and Stanimirović, Zoran},
  title     = {Oxidative stress and DNA damage in peripheral blood mononuclear cells from normal, obese, prediabetic and diabetic persons exposed to thyroid hormone in vitro},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {16},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23169072},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285988},
  year      = {2022},
  abstract  = {Diabetes, a chronic group of medical disorders characterized byhyperglycemia, has become a global pandemic. Some hormones may influence the course and outcome of diabetes, especially if they potentiate the formation of reactive oxygen species (ROS). There is a close relationship between thyroid disorders and diabetes. The main objective of this investigation was to find out whether peripheral blood mononuclear cells (PBMCs) are more prone to DNA damage by triiodothyronine (T\(_3\)) (0.1, 1 and 10 μM) at various stages of progression through diabetes (obese, prediabetics, and type 2 diabetes mellitus—T2DM persons). In addition, some biochemical parameters of oxidative stress (catalase-CAT, thiobarbituric acid reactive substances—TBARS) and lactate dehydrogenase (LDH) were evaluated. PBMCs from prediabetic and diabetic patients exhibited increased sensitivity for T\(_3\) regarding elevated level of DNA damage, inhibition of catalase, and increase of TBARS and LDH. PBMCs from obese patients reacted in the same manner, except for DNA damage. The results of this study should contribute to a better understanding of the role of thyroid hormones in the progression of T2DM.},
  language  = {en}
}
@article{MatsusakaChenAriasLozaetal.2022,
  author    = {Matsusaka, Yohji and Chen, Xinyu and Arias-Loza, Paula and Werner, Rudolf A. and Nose, Naoko and Sasaki, Takanori and Rowe, Steven P. and Pomper, Martin G. and Lapa, Constantin and Higuchi, Takahiro},
  title     = {In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [\(^{18}\)F]Me4FDG PET in Rats},
  series = {Molecular Imaging},
  volume    = {2022},
  journal   = {Molecular Imaging},
  doi       = {10.1155/2022/4635171},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300708},
  year      = {2022},
  abstract  = {Background. Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[\(^{18}\)F]fluoro-D-glucopyranoside ([\(^{18}\)F]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport. Methods. We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose ([\(^{18}\)F]FDG), or the SGLT-targeting agent, [\(^{18}\)F]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [18F]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV). Results. Serving as reference, intestinal administration of [\(^{18}\)F]FDG led to slow absorption with retention of \% of administered radioactivity at 15 min. [\(^{18}\)F]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of \% (). Intraintestinal phlorizin led to marked increase of [\(^{18}\)F]Me4FDG uptake (15 min, \%; vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [\(^{18}\)F]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (\%ID/g at 60 min, vs. untreated controls, ; ). Conclusion. As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [\(^{18}\)F]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [\(^{18}\)F]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies.},
  language  = {en}
}
@article{OckermannHeadleyLizioetal.2021,
  author    = {Ockermann, Philipp and Headley, Laura and Lizio, Rosario and Hansmann, Jan},
  title     = {A Review of the Properties of Anthocyanins and Their Influence on Factors Affecting Cardiometabolic and Cognitive Health},
  series = {Nutrients},
  volume    = {13},
  journal   = {Nutrients},
  number    = {8},
  issn      = {2072-6643},
  doi       = {10.3390/nu13082831},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245116},
  year      = {2021},
  abstract  = {The incidence of cardiovascular and metabolic diseases has increased over the last decades and is an important cause of death worldwide. An upcoming ingredient on the nutraceutical market are anthocyanins, a flavonoid subgroup, abundant mostly in berries and fruits. Epidemiological studies have suggested an association between anthocyanin intake and improved cardiovascular risk, type 2 diabetes and myocardial infarct. Clinical studies using anthocyanins have shown a significant decrease in inflammation markers and oxidative stress, a beneficial effect on vascular function and hyperlipidemia by decreasing low-density lipoprotein and increasing high-density lipoprotein. They have also shown a potential effect on glucose homeostasis and cognitive decline. This review summarizes the effects of anthocyanins in in-vitro, animal and human studies to give an overview of their application in medical prevention or as a dietary supplement.},
  language  = {en}
}
@article{SchneiderGutjahrLengsfeldRitzetal.2014,
  author    = {Schneider, Andreas and Gutjahr-Lengsfeld, Lena and Ritz, Eberhard and Scharnagl, Hubert and Gelbrich, G{\"o}tz and Pilz, Stefan and Macdougall, Iain C. and Wanner, Christoph and Drechsler, Christiane},
  title     = {Longitudinal Assessments of Erythropoietin-Stimulating Agent Responsiveness and the Association with Specific Clinical Outcomes in Dialysis Patients},
  series = {Nephron Clinical Practice},
  volume    = {128},
  journal   = {Nephron Clinical Practice},
  number    = {1-2},
  issn      = {1660-2110},
  doi       = {10.1159/000367975},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196511},
  pages     = {147-152},
  year      = {2014},
  abstract  = {Background: Dose requirements of erythropoietin-stimulating agents (ESAs) can vary considerably over time and may be associated with cardiovascular outcomes. We aimed to longitudinally assess ESA responsiveness over time and to investigate its association with specific clinical end points in a time-dependent approach. Methods: The German Diabetes and Dialysis study (4D study) included 1,255 diabetic dialysis patients, of whom 1,161 were receiving ESA treatment. In those patients, the erythropoietin resistance index (ERI) was assessed every 6 months during a median follow-up of 4 years. The association between the ERI and cardiovascular end points was analyzed by time-dependent Cox regression analyses with repeated ERI measures. Results: Patients had a mean age of 66 ± 8.2 years; 53\% were male. During follow-up, a total of 495 patients died, of whom 136 died of sudden death and 102 of infectious death. The adjusted and time-dependent risk for sudden death was increased by 19\% per 5-unit increase in the ERI (hazard ratio, HR = 1.19, 95\% confidence interval, CI = 1.07-1.33). Similarly, mortality increased by 25\% (HR = 1.25, 95\% CI = 1.18-1.32) and infectious death increased by 27\% (HR = 1.27, 95\% CI = 1.13-1.42). Further analysis revealed that lower 25-hydroxyvitamin D levels were associated with lower ESA responsiveness (p = 0.046). Conclusions: In diabetic dialysis patients, we observed that time-varying erythropoietin resistance is associated with sudden death, infectious complications and all-cause mortality. Low 25-hydroxyvitamin D levels may contribute to a lower ESA responsiveness.},
  language  = {en}
}
@article{Koepsell2020,
  author    = {Koepsell, Hermann},
  title     = {Glucose transporters in brain in health and disease},
  series = {Pfl{\"u}gers Archiv - European Journal of Physiology},
  volume    = {472},
  journal   = {Pfl{\"u}gers Archiv - European Journal of Physiology},
  issn      = {0031-6768},
  doi       = {10.1007/s00424-020-02441-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232746},
  pages     = {1299-1343},
  year      = {2020},
  abstract  = {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},
  language  = {en}
}
@article{Koepsell2020,
  author    = {Koepsell, Hermann},
  title     = {Glucose transporters in the small intestine in health and disease},
  series = {Pfl{\"u}gers Archiv - European Journal of Physiology},
  volume    = {472},
  journal   = {Pfl{\"u}gers Archiv - European Journal of Physiology},
  issn      = {0031-6768},
  doi       = {10.1007/s00424-020-02439-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232552},
  pages     = {1207-1248},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}
@article{PerkovicAgarwalFiorettoetal.2016,
  author    = {Perkovic, Vlado and Agarwal, Rajiv and Fioretto, Paola and Hemmelgarn, Brenda R. and Levin, Adeera and Thomas, Merlin C. and Wanner, Christoph and Kasiske, Bertram L. and Wheeler, David C. and Groop, Per-Henrik},
  title     = {Management of patients with diabetes and CKD: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) controversies conference},
  series = {Kidney International},
  volume    = {90},
  journal   = {Kidney International},
  number    = {6},
  doi       = {10.1016/j.kint.2016.09.010},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186599},
  pages     = {1175-1183},
  year      = {2016},
  abstract  = {The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population.},
  language  = {en}
}
@article{DirimanovHoegger2019,
  author    = {Dirimanov, Stoyan and H{\"o}gger, Petra},
  title     = {Screening of inhibitory effects of polyphenols on Akt-phosphorylation in endothelial cells and determination of structure-activity features},
  series = {Biomolecules},
  volume    = {9},
  journal   = {Biomolecules},
  number    = {6},
  issn      = {2218-273X},
  doi       = {10.3390/biom9060219},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197333},
  pages     = {219},
  year      = {2019},
  abstract  = {Polyphenols exert beneficial effects in type 2 diabetes mellitus (T2DM). However, their mechanism of action remains largely unknown. Endothelial Akt-kinase plays a key role in the pathogenesis of cardiovascular complications in T2DM and therefore the modulation of its activity is of interest. This work aimed to characterize effects of structurally different polyphenols on Akt-phosphorylation (pAkt) in endothelial cells (Ea.hy926) and to describe structure-activity features. A comprehensive screening via ELISA quantified the effects of 44 polyphenols (10 µM) on pAkt Ser473. The most pronounced inhibitors were luteolin (44 ± 18\%), quercetin (36 ± 8\%), urolithin A (35 ± 12\%), apigenin, fisetin, and resveratrol; (p < 0.01). The results were confirmed by Western blotting and complemented with corresponding experiments in HUVEC cells. A strong positive and statistically significant correlation between the mean inhibitory effects of the tested polyphenols on both Akt-residues Ser473 and Thr308 (r = 0.9478, p = 0.0003) was determined by immunoblotting. Interestingly, the structural characteristics favoring pAkt inhibition partially differed from structural features enhancing the compounds' antioxidant activity. The present study is the first to quantitatively compare the influence of polyphenols from nine different structural subclasses on pAkt in endothelial cells. These effects might be advantageous in certain T2DM-complications involving over-activation of the Akt-pathway. The suggested molecular mode of action of polyphenols involving Akt-inhibition contributes to understanding their effects on the cellular level.},
  language  = {en}
}
@article{WernerEisslerHayakawaetal.2018,
  author    = {Werner, Rudolf A. and Eissler, Christoph and Hayakawa, Nobuyuki and Arias-Loza, Paula and Wakabayashi, Hiroshi and Javadi, Mehrbod S. and Chen, Xinyu and Shinaji, Tetsuya and Lapa, Constantin and Pelzer, Theo and Higuchi, Takahiro},
  title     = {Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {17631},
  doi       = {10.1038/s41598-018-35986-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171765},
  year      = {2018},
  abstract  = {In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5\%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.},
  language  = {en}
}
@article{StraussMoskalenkoTiurbeetal.2012,
  author    = {Strauss, Armin and Moskalenko, Vasily and Tiurbe, Christian and Chodnevskaja, Irina and Timm, Stephan and Wiegering, Verena A. and Germer, Chrioph Thomas and Ulrichs, Karin},
  title     = {Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing Diabetes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75119},
  year      = {2012},
  abstract  = {Purpose: Preclinical experiments on large animals are indispensable for evaluating the effectiveness of diabetes therapies. Miniature swine are well suited for such studies due to their physiological and pathophysiological responses. Methods: We compare two methods for inducing diabetes in Goettingen minipigs (GMP), in five with the beta cell toxin streptozotocin (STZ) and in five other GMP by total pancreatectomy (PE). Glucose homeostasis was assessed with the intravenous glucose-tolerance test (IVGTT) and continual monitoring of interstitial glucose levels. At conclusion of the observation period, the pancreata were examined histologically. Three non-diabetic GMP served as control group. Results: The IVGTT revealed markedly diabetic profiles in both GMP groups. STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive cells in the pancreas. PE-GMP survived the total pancreatectomy only with intensive postoperative care. Conclusions: Although both methods reliably induced diabetes in GMP, the PE-GMP clearly had more health problems and required a greater expenditure of time and resources. The PE-GMP model, however, was better at eliminating endogenous insulin and C-peptide than the STZ-GMP model.},
  subject      = {G{\"o}ttingen},
  language  = {en}
}