Insulin-like peptide 5 (INSL5) is a gut hormone produced by L-cells in the colorectal epithelium and may play a role in the regulation of metabolic processes. The biological role of INSL5 is poorly investigated and nothing is known about the role of this hormone in obese and lean humans. Two cohorts were analyzed in the study. In the first cohort (n=76) the relationship between serum levels of INSL5 and different metabolic and hormonal parameters in obese and lean men and women were investigated. In the second cohort 14 male subjects underwent bariatric surgery. Circulating levels of INSL5 were then measured before and after interventions.We report for the first time that circulating INSL5 interacts with multiple metabolic and hormonal variables in lean and obese men and women and is affected by bariatric surgery. Serum levels of INSL5 negatively correlated with testosterone and blood lipids but positively with cortisol in obese men. In contrast to males, obese women had a strong negative correlation of plasma levels of INSL5 with C-reactive protein (CRP). We observed that adipose tissue loss after bariatric surgery significantly reduced serum levels of INSL5 in obese men with and without Type 2 Diabetes Mellitus (T2DM) that was associated with the restoration of circulating levels of testosterone. All together, our data demonstrated that INSL5 may interact with some metabolic parameters in obese humans and this process is dependent of gender and obesity state.

Background: The C57BL/6JRj and C57BL/6NTac mouse substrains are different in their response to high fat diet induced obesity, despite a homology of 98%. The C57BL/6JRj strain has a mutation in the nicotinamide nucleotide transhydrogenase (NNT) gene. Aim of the study was to examine the role of NNT in high fat diet induced obesity.

Background and aims: Secreted frizzled-related protein-5 (SFRP5) has been identified to antagonize Wnt signalling as a central pathway of adipogenesis which is related to metabolic disorders. Mice with a disruption of SFRP5 have elevated fasting glucose and insulin levels upon high fat and high-sucrose diet. SFRP5 expression in mature adipocytes correlates with increasing adiposity.

Einleitung: Ambulante Adipositastherapieprogramme bei denen temporär eine Nahrungsergänzung eingesetzt wird, finden zunehmende Akzeptanz.

Einleitung: Die Internationale Diabetes-Föderation (IDF) hat im Jahr 2005 eine modifizierte Definition des Metabolischen Syndroms (MS) vorgestellt, aus der durchaus eine erhebliche Zunahme der MS-Prävalenz resultieren könnte.

Einleitung: Das metabolische Syndrom (MS) erhöht das Risiko, einen Diabetes mellitus Typ 2 oder eine koronare Herzkrankheit zu entwickeln um das 5 bzw. 4-fache (1). Moderne Interventionsstrategien sind erforderlich.

Effects of a Protein Optimized Diet Combined with Moderate Resistance Training on the Postoperative Course in Older Patients with Hip Fracture

The whole-cell patch-clamp technique was used to record current responses to nucleotides in HEK 293 cells transiently transfected with the human (h) P2X(3) receptor. When GDP-beta-S was included into the pipette solution, UTP at concentrations which did not alter the holding current, facilitated the alpha,beta-methylene ATP (alpha,beta-meATP)-induced current. The substitution of Ser/Thr residues situated within protein kinase C (PKC) consensus phosphorylation sites of the P2X(3) receptor ecto-domain by the neutral amino acid Ala either abolished (T134A, S178A) or did not alter (T196A, S269A) the UTP-induced potentiation of the alpha,beta-meATP current. The substitution of the same Ser/Thr residues in all four PKC sites by the negatively charged Asp prevented the potentiation by UTP. The Asp mutations abolished the first, fast offset time-constant, but did not alter, or in the case of S269D even increased, the second, slow offset time-constant; at the same time such mutations invariably increased the onset time-constant and massively depressed the peak current amplitude. None of the Ala mutations (with the exception of S269A) influenced the time-course of desensitisation or the peak current amplitude. It is concluded that constitutive activation of PKC sites at the ecto-domain of the hP2X(3) receptor both abolishes the UTP-induced potentiation of the alpha,beta-meATP current and accelerates its rate of desensitisation.

The whole-cell patch-clamp technique was used to record current responses to nucleotides and nucleosides in human embryonic kidney HEK293 cells transfected with the human purinergic P2X3 receptor. When guanosine 5′-O-(3-thiodiphosphate) was included into the pipette solution, UTP at concentrations that did not alter the holding current facilitated the α,β-methylene ATP (α,β-meATP)-induced current. ATP and GTP, but not UDP or uridine, had an effect similar to that of UTP. Compounds known to activate protein kinase C (PKC) acted like the nucleoside triphosphates investigated, whereas various PKC inhibitors invariably reduced the effects of both PKC activators and UTP. The substitution by Ala of Ser/Thr residues situated within PKC consensus sites of the P2X3 receptor ectodomain either abolished (PKC2 and PKC3; T134A, S178A) or did not alter (PKC4 and PKC6; T196A, S269A) the UTP-induced potentiation of the α,β-meATP current. Both the blockade of ecto-protein kinase C activity and the substitution of Thr-134 or Ser-178 by Ala depressed the maximum of the concentration-response curve for α,β-meATP without altering the EC50 values. Molecular simulation of the P2X3 receptor structure indicated no overlap between assumed nucleotide binding domains and the relevant phosphorylation sites PKC2 and PKC3. α,β-meATP-induced currents through native homomeric P2X3 receptors of rat dorsal root ganglia were also facilitated by UTP. In conclusion, it is suggested that low concentrations of endogenous nucleotides in the extracellular space may prime the sensitivity of P2X3 receptors toward the effect of subsequently applied (released) higher agonistic concentrations. The priming effect of nucleotides might be attributable to a phosphorylation of PKC sites at the ectodomain of P2X3 receptors.

Lifestyle intervention programmes for treatment of over-weight/ obesity have to consider evidence-based guidelines and should fulfil practical needs. The revised,,ICH nehme ab" (I lose weight") programme of the German Society for Nutrition (DGE) was designed as an advisor- supported self-help programme. It was evaluated in two samples of overweight/ obese individuals comprising 96 females, BMI: 32.2 +/- 5.4 kg/m(2) and 23 males, BMI: 32.8 +/- 4.3 kg/m(2) according to defined criteria. Mean weight loss in the Intention-ToTreat (ITT) und Per-Protocol (PP) analyses was 2.3 +/- 4.4 kg (ITT) and 2.8 +/- 4.6 kg (PP) in females and 4.1 +/- 5.7 kg (ITT) and 4.7 +/- 6.3 kg (PP) in men after 12 month. According to the ITT analysis 80 % of the participants reduced weight or kept it constant, 34 % reduced weight by 5 % or more and 10 % reduced weight by 10 % or more. An analysis of the dietary behaviour has shown that the intake of carbohydrates in females increased from 46 to 49 %, whereas fat intake decreased from 35 to 32 % (ITT, p < 0,0001). The majority of participants has found the programme useful and would recommend it to their friends.The DGE programme "I lose weight" leads to a moderate but significant weight loss and to positive dietary changes when used in an advisor- supported approach.

Applying the MIRA (German acronym for losing weight intelligently) concept, weight-losing programs were tested for guideline conformity and suitability in practice. The core of the concept comprises instruments for the analysis and evaluation of quality criteria for weight-reduction programs. A total of 116 men and women participated in the BCM program of PreCon GmbH & Co. KG, and the "Ich nehme ab" (l'm slimming) program (designed as a self-help aid) of the Deutsche Gesellschaft für Ernährung (German Society for Nutrition), and received counseling over a period of one year. Initial results of follow-up at 40 weeks showed a weight reduction of at least 5% in 66% of all participants, and at least 10% in 24%. The weight loss correlated with the number of counselings. On the basis of the 89 questionnaires evaluated to date, quality of life as measured by the IWQOL-Lite score showed an improvement in 80% of the subjects. These preliminary results indicate that the MIRA concept would appear to be a suitable quality control tool for obesity treatment programs.