Biomedical subjects

Matthias Blüher

Publications and source records attributed to Matthias Blüher.

23 records · Page 2Linked to original sources

PubMed2003

Extended longevity in mice lacking the insulin receptor in adipose tissue.

Caloric restriction has been shown to increase longevity in organisms ranging from yeast to mammals. In some organisms, this has been associated with a decreased fat mass and alterations in insulin/insulin-like growth factor 1 (IGF-1) pathways. To further explore these associations with enhanced longevity, we studied mice with a fat-specific insulin receptor knockout (FIRKO). These animals have reduced fat mass and are protected against age-related obesity and its subsequent metabolic abnormalities, although their food intake is normal. Both male and female FIRKO mice were found to have an increase in mean life-span of approximately 134 days (18%), with parallel increases in median and maximum life-spans. Thus, a reduction of fat mass without caloric restriction can be associated with increased longevity in mice, possibly through effects on insulin signaling.

Adipose Tissue↗

PubMed2003

Analysis of the relationship between the Pro12Ala variant in the PPAR-gamma2 gene and the response rate to therapy with pioglitazone in patients with type 2 diabetes.

OBJECTIVE: To investigate the influence of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene variants on the response rate to therapy with the thiazolidinedione (TZD) pioglitazone, because in vitro studies have suggested that genetic variants of the PPAR-gamma gene may influence the drug efficacy of TZD. RESEARCH DESIGN AND METHODS: A total of 131 patients were treated in an open-label, randomized, multicenter study with pioglitazone (45 mg o.d.) during a course of >or=26 weeks. Response to the pioglitazone therapy was defined by either a >20% decrease in fasting plasma glucose or a >15% decrease in HbA(1c) values after 26 weeks of pioglitazone treatment. We evaluated the association between the PPAR-gamma genotype and the response rate to pioglitazone treatment. RESULTS: The Pro12Ala and the Pro12Pro variants in the PPAR-gamma gene are not associated with the response rate to pioglitazone treatment in patients with type 2 diabetes. However, we identified initial fasting plasma glucose level >11.0 mmol/l, HbA(1c) value >9.0%, BMI >32 kg/m(2), and fasting C-peptide concentrations at baseline >2.5 pmol/l as predominant confounding factors for the responder frequency to pioglitazone treatment. CONCLUSIONS: The Pro12Ala variant in the PPAR-gamma gene does not affect the therapy efficacy of pioglitazone, suggesting that the drug-treatment response is independent from pharmacogenetic effects between PPAR-gamma and its ligand pioglitazone. Whether the Ala12Ala genotype plays a role in the response rate to TZD therapy remains to be determined.

Aged↗

PubMed2002

Evaluation of a computer based interactive diabetes education program designed to train the estimation of the energy or carbohydrate contents of foods.

The objective of this study was to evaluate a computer based interactive diabetes education program designed to train patients with diabetes to correctly estimate the energy or carbohydrate contents of foods. The acceptance and the operator convenience of the program were evaluated with an integrated program and written questionnaires. The training success was calculated for each user from the data sets after multiple repetitions of the same exercise. Age, weight, type of diabetes, previous training and computer experience of 126 patients with type 1 or 2 diabetes from three different German diabetes centres were documented. The evaluation of the computer program indicated a good acceptance and operator convenience. Moreover, there was a significant training success in patients who have never used a structured diabetes education program before. Therefore, the potential impact of the program is to support but not to replace structured diabetes education programs and to further motivate and attract patients to diabetes education programs.

Computer-Assisted Instruction↗

PubMed2002

Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance.

Insulin signaling in adipose tissue plays an important role in lipid storage and regulation of glucose homeostasis. Using the Cre-loxP system, we created mice with fat-specific disruption of the insulin receptor gene (FIRKO mice). These mice have low fat mass, loss of the normal relationship between plasma leptin and body weight, and are protected against age-related and hypothalamic lesion-induced obesity, and obesity-related glucose intolerance. FIRKO mice also exhibit polarization of adipocytes into populations of large and small cells, which differ in expression of fatty acid synthase, C/EBP alpha, and SREBP-1. Thus, insulin signaling in adipocytes is critical for development of obesity and its associated metabolic abnormalities, and abrogation of insulin signaling in fat unmasks a heterogeneity in adipocyte response in terms of gene expression and triglyceride storage.

Adipocytes↗

PubMedDate not supplied

The polygenetically inherited metabolic syndrome of WOKW rats is associated with insulin resistance and altered gene expression in adipose tissue.

BACKGROUND: Wistar Ottawa Karlsburg W (RT1u) rats (WOKW) develop a complete metabolic syndrome closely resembling the human disease. The aim of this study was to characterize the phenotype of adipose tissue in WOKW rats with regard to adipocyte metabolism, insulin resistance, and gene expression and thus to define the phenotype more precisely. METHODS: Glucose metabolism, insulin sensitivity, and gene expression of key adipocyte genes, including adiponectin, interleukin 6 (Il6), 11 beta-hydroxysteroid dehydrogenase (11beta Hsd), peroxisome proliferator-activated receptor gamma (Ppar gamma), forkhead box O1 (Foxo1), glucose transporter 4 (Glut4), CCAAT/enhancer binding protein (C/ebp alpha), and fatty acid synthase (Fasn) were characterized in adipocytes from epididymal and subcutaneous fat depots of 28-week-old male WOKW rats and Dark Agouti (DA) controls. RESULTS: WOKW rats display decreased insulin-stimulated glucose uptake and decreased insulin sensitivity during lipogenesis and lipolysis in isolated adipocytes. The severe insulin resistance predominantly in epididymal adipose tissue of WOKW rats is associated with a 10-fold decrease in adipocyte adiponectin gene expression, decreased Ppar gamma, but increased Foxo1 gene expression compared to DA rats. CONCLUSIONS: Insulin resistance in adipose tissue is associated with altered adipocyte gene expression in WOKW rats, additionally completing the picture of the metabolic syndrome in this animal model. This fact not only qualifies the WOKW rat for further detailed analysis of genetic determinants of metabolic syndrome but also highlights its suitability for pharmacological research.

Adipocytes↗