Publications by authors named "Freyse E"

Cardiomyopathies such as idiopathic dilated cardiomyopathy (DCM), Chagas' cardiomyopathy and Peripartum cardiomyopathy present with autoantibodies against G-protein coupled receptors (GPCR-AABs) that agonistically activate their receptors. For the treatment of "agonistic autoantibody diseases" and in particular DCM, the removal of the GPCR-AABs by immunoadsorption (IA) has been studied with convincing patient benefit. To overcome cost and logistics problems of IA, the application of the aptamer BC007 for in vivo neutralization of GPCR-AABs could help.

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Secretory peptides and proteins are frequently modified by pyroglutamic acid (pE, pGlu) at their N-terminus. This modification is catalyzed by the glutaminyl cyclases QC and isoQC. Here, we decipher the roles of the isoenzymes by characterization of IsoQC-/- mice.

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Autoantibodies (AABs) against the second extracellular loop of the beta1-receptor (beta1(II)-AABs) are found as a pathogenic driver in patients with idiopathic dilated cardiomyopathy, Chagas cardiomyopathy, peripartum cardiomyopathy, and myocarditis, and have been increasingly seen as a treatment target. We recently identified an aptamer (single short DNA strand) that specifically binds and neutralizes beta1(II)-AABs. Via application of this aptamer, a new treatment strategy for diseases associated with the cardio-pathogenic beta1(II)-AABs could be developed.

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Background: Application of immunoapheresis to eliminate pathogenic autoantibodies targeting the second extracellular loop of the β1-receptor (β1-AABs) is currently investigated in patients with cardiomyopathy. Aptamers (single short DNA or RNA strands) are a new class of molecules that bind to a specific target molecule. This property qualifies aptamers for potential use in the apheresis technique.

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The importance of glycaemic variability (GV) as a factor in the pathophysiology of cellular dysfunction and late diabetes complications is currently a matter of debate. However, there is mounting evidence from in vivo and in vitro studies that GV has adverse effects on the cascade of physiological processes that result in chronic β-cell dysfunctions. Glucose fluctuations more than sustained chronic hyperglycaemia can induce excessive formation of reactive oxygen (ROS) and reactive nitrogen species (RNS), ultimately leading to apoptosis related to oxidative stress.

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Acute and chronic inflammatory disorders are characterized by detrimental cytokine and chemokine expression. Frequently, the chemotactic activity of cytokines depends on a modified N-terminus of the polypeptide. Among those, the N-terminus of monocyte chemoattractant protein 1 (CCL2 and MCP-1) is modified to a pyroglutamate (pE-) residue protecting against degradation in vivo.

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Glutaminyl cyclases (QCs) catalyze the formation of pyroglutamate (pGlu) residues at the N terminus of peptides and proteins. Hypothalamic pGlu hormones, such as thyrotropin-releasing hormone and gonadotropin-releasing hormone are essential for regulation of metabolism and fertility in the hypothalamic pituitary thyroid and gonadal axes, respectively. Here, we analyzed the consequences of constitutive genetic QC ablation on endocrine functions and on the behavior of adult mice.

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GIP metabolite [GIP (3-42)] and GLP-1 metabolite [GLP-1 (9-36) amide] have been reported to differ with regard to biological actions. Systemic DPP-4 inhibition can therefore reveal different actions of GIP and GLP-1. In catheter wearing Wistar rats, insulinotropic effects of equipotent doses of GIP (2.

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Objective: Glucose fluctuations trigger activation of oxidative stress, a main mechanism leading to secondary diabetes complications. We evaluated the relationship between glycemic variability and beta-cell dysfunction.

Research Design And Methods: We conducted a cross-sectional study in 59 patients with type 2 diabetes (aged 64.

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Given the importance of glucose variability in the development of diabetic complications, the present study used continuous glucose monitoring (CGM) to determine various indices of glucose variability and to investigate their relationships with conventional measures of chronic sustained hyperglycemia. We examined 53 women and 61 men, aged 36-79 years afflicted with type 2 diabetes for 1-24 years. The following indices of glycemic variability were computed from CGM data sets: mean amplitude of glycemic excursions (MAGE), CGM glucose range, interquartile range (IQR), SD-score, and average daily risk range (ADRR).

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Aim: Incretin enhancers are a new class of antidiabetic drugs with promising therapeutic potential for type 2 diabetes. Therapeutic intervention in prediabetes is an attractive strategy for preventing or delaying diabetes onset. The aim of the present study was to investigate the therapeutic effects of incretin enhancement on incipient impaired glucose tolerance (iIGT) and manifest IGT (mIGT) using the dipeptidyl peptidase IV (DPP-4) inhibitor P32/98- and fatty Zucker rat (ZR, fa/fa) as a model.

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Background: The Karlsburg Diabetes Management System (KADIS) was developed over almost two decades by modeling physiological glucose-insulin interactions. When combined with the telemedicine-based communication system TeleDIAB and a continuous glucose monitoring system (CGMS), KADIS has the potential to provide effective, evidence-based support to doctors in their daily efforts to optimize glycemic control.

Methods: To demonstrate the feasibility of improving diabetes control with the KADIS system, an experimental version of a telemedicine-based diabetes care network was established, and an international, multicenter, pilot study of 44 insulin-treated patients with type 1 and 2 diabetes was performed.

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Objective: We sought to assess the benefit of the Karlsburg Diabetes Management System (KADIS) in conjunction with the continuous glucose monitoring system (CGMS) in an outpatient setting.

Research Design And Methods: A multicentric trial was performed in insulin-treated outpatients (n = 49), aged 21-70 years, with a mean diabetes duration of 14.2 years.

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To determine the relationships between HbA1c, characteristics of hyperglycemia and glycemic variability in well-controlled type 2 diabetes (HbA1c<7.0%), we studied 63 primary-care patients (36 men and 27 women), aged 34-75 years, with type 2 diabetes for 2-32 years using a continuous glucose monitoring system (CGMS) and standardized meal test (MMT). Duration of hyperglycemia (>8.

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Aims/hypothesis: In non-diabetic people, insulin levels in the liver are two-fold higher than those in the systemic circulation. In contrast, patients with type 1 diabetes have similar hepatic and systemic insulin levels because insulin is administered peripherally. The aim of this study was to compare the effects of systemic (SI) and pre-portal (PI) insulin administration on energy, glucose and protein metabolism in chronic insulin-dependent ketosis-prone diabetic dogs.

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Increased synthesis rate of fibrinogen, an independent risk factor for cardiovascular disease, was recently reported in obese insulin-resistant female adolescents with chronic elevated nonesterified fatty acids (NEFA). It is unknown whether a short-term change of NEFA concentrations controls hepatic fibrinogen synthesis. Therefore, 10 healthy male volunteers (24.

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A pharmacological concentration of glucagon-like peptide-1 (GLP-1) in the insulin-deficient state clearly decreases the blood glucose level. Therefore, this study was designed to evaluate a putatively relevant effect of the gastrointestinal peptide as an adjuvant to insulin replacement therapy. GLP-1 (GLP-1(7-36) amide 10 pmol x kg(-1) x min(-1)) was infused intravenously over 8 hours in nine fasting, C-peptide-negative diabetic dogs.

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For verifying catabolic states in insulin-dependent patients and dogs the method estimating urea production rates with 13C and with doubly 15N labeled urea, respectively, has been established. For a fast steady state of urea tracer dilution, a prime of 600 times the continuous infusion rate had to be injected. Urea was isolated from plasma samples by protein precipitation and cation exchange chromatography with a consecutive derivatization of the dried urea fraction (trimethylsilyl derivatives).

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Abstract For verifying catabolic states in insulin-dependent patients and dogs the method estimating urea production rates with (13)C and with doubly (15)N labeled urea, respectively, has been established. For a fast steady state of urea tracer dilution, a prime of 600 times the continuous infusion rate had to be injected. Urea was isolated from plasma samples by protein precipitation and cation exchange chromatography with a consecutive derivatization of the dried urea fraction (trimethylsilyl derivatives).

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To establish potential effects of glucagon-like peptide I (GLP-I) on blood glucose control in insulin-deficient states, GLP-I [GLP-I(7-36) amide; 10 pmol x kg(-1) x min(-1)] was infused intravenously in six fasting, canine C-peptide-negative, chronically diabetic dogs for 8 h. Blood samples were saved for the analysis of hormones, metabolites, and turnover rates of glucose (6-(3)H-glucose), alanine (U-(14)C-alanine), and urea ((15)N(2)-urea) starting 22 h after the last subcutaneous dose of exogenous insulin. Circulating plasma GLP-I levels rose under infusion from 2.

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In IDDM, the gluconeogenic turnover of amino acids is increased even if glycemia is well controlled and may be restored to normal by means of prehepatic insulin substitution. Therefore, the present study was designed 1) to investigate the influence of route of insulin administration (portal versus peripheral) on the urea production rate, which is considered to measure amino acid catabolism, and 2) to elucidate the impact of different food-protein intake. Paired studies were conducted in chronic insulin-dependent diabetic dogs maintained normoglycemic.

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In our physiology laboratory course we introduced several simple but instructive experiments in which medical students make observations on their own blood cells. In this experiment, students measured and discussed the effect of different temperatures on Na+ and K+ distribution between blood cells and plasma. In venous blood of 35 female and 64 male students, plasma (extracellular) [Na+] and [K+] were measured with ion-selective electrodes immediately after blood sampling and successively four times in intervals of 1 h in three samples stored at 1, 20, and 37 degrees C.

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The replacement of insulinogenic function in insulin-dependent diabetes has to restore the feedback between intracorporal glucose and insulin. This has been accomplished by the following approaches: (a) the so-called open-loop insulin treatment by means of injections or pumps, employing laboratory or other extracorporal analytical devices and closing the feedback at large intervals only; (b) transplantation of insulin producing tissue and the bioartificial pancreas, employing the natural beta-cell both for glucose sensing and insulin delivery; (c) implanted artificial drug delivery systems providing chemical feedback between intracorporal glucose and insulin release from a nonrefillable reservoir of limited capacity; (d) the intracorporal or paracorporal artificial beta-cell comprising a glucose sensor (electrochemical or other type) that permanently delivers the signal to the computer-controlled insulin pump. This artificial device works on the basis of an algorithm of glucose-dependent insulin provision, compensating for the lack of other regulators, for the site of insulin administration, which is usually posthepatic, and for the kinetic properties of sensing system, e.

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To verify a structured model of the glucose-insulin system, metabolic measurements were compared with model-based simulations in insulin-dependent diabetic dogs which had been previously identified in terms of model parameters. Glycaemia, glucosuria, plasma insulin, and the rates of appearance Ra and disappearance Rd of glucose (kinetics of double-labelled glucose, evaluated according to Steele's equation in its non-steady-state version) were observed under the following conditions, starting from normoglycaemia during glucose-controlled insulin infusion (GCII): (I) insulin withdrawal, (II) insulin withdrawal and glucose infusion, (III) constant i.v.

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To quantitate the degree of glycemic control in relation to insulin doses required on the peritoneal route of administration, insulin dependent diabetic dogs instrumented with chronic peritoneal and venous catheters and with access devices for serial peritoneal injections, were treated with regular insulin at random order as follows: (1) subcutaneous injections, (2) peritoneal injections, (3) continuous intravenous infusion, (4) continuous peritoneal infusion. Metabolic profiles were taken over 24 h after an average duration of treatment of 2 weeks and were compared to data obtained in nondiabetic animals. Insulin doses and postprandial increase in peripheral insulinemia were higher and glycemic control was worse on peritoneal vs.

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