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H Staiger

Publications and source records attributed to H Staiger.

17 recordsLinked to original sources
PubMed2005

Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat.

AIMS/HYPOTHESIS: The adipokine adiponectin has insulin-sensitising, anti-atherogenic and anti-inflammatory properties. Recently, the genes for mouse and human adiponectin receptor-1 (ADIPOR1) and -2 (ADIPOR2) have been cloned. The aim of this study was to investigate whether genetic variants of the genes encoding ADIPOR1 and ADIPOR2 play a role in human metabolism. MATERIALS AND METHODS: We screened ADIPOR1 and ADIPOR2 for polymorphisms and determined their association with glucose metabolism, lipid metabolism, an atherogenic lipid profile and inflammatory markers in 502 non-diabetic subjects. A subgroup participated in a longitudinal study; these subjects received diet counselling and increased their physical activity. RESULTS: We identified six variants of ADIPOR1 and seven variants of ADIPOR2. A single-nucleotide polymorphism (SNP) in the putative promoter region 8503 bp upstream of the translational start codon (-8503 G/A) of ADIPOR1 (frequency of allele A=0.31) was in almost complete linkage disequilibrium with another SNP (-1927 T/C) in intron 1. Subjects carrying the -8503 A and -1927 C alleles had lower insulin sensitivity, as estimated from a 75 g OGTT (p=0.04) and determined during a euglycaemic clamp (n=295, p=0.04); they also had higher HbA(1)c levels (p=0.02) and, although the difference was not statistically significant, higher liver fat (n=85, determined by proton magnetic resonance spectroscopy, p=0.056) (all p values are adjusted for age, sex and percentage of body fat). In the longitudinal study (n=45), the -8503 A and -1927 C alleles were associated with lower insulin sensitivity (p=0.03) and higher liver fat (p=0.02) at follow-up compared with the -8503 G and -1927 T alleles, independently of basal measurements, sex and baseline and follow-up percentage of body fat. CONCLUSIONS/INTERPRETATION: The present findings suggest that the -8503 G/A SNP in the promoter or the -1927 T/C SNP in intron 1 of ADIPOR1 may affect insulin sensitivity and liver fat in humans.

Adipose Tissue↗
PubMed2005

Adiponectin is functionally active in human islets but does not affect insulin secretory function or beta-cell lipoapoptosis.

CONTEXT: The adipokine adiponectin has insulin-sensitizing, antiatherogenic, and antiinflammatory properties. Mouse and human adiponectin receptor-1 and -2 have been cloned, both of which are expressed in various tissues and mediate effects of globular and full-length adiponectin. Whether adiponectin affects insulin secretion and beta-cell apoptosis and whether plasma adiponectin is associated with beta-cell function in humans is under investigation. DESIGN AND METHODS: In human islets from multiorgan donors, we investigated expression of adiponectin receptor-1 and -2. Furthermore, glucose-stimulated insulin secretion was determined by RIA. In addition, we investigated fatty acid-induced beta-cell apoptosis by terminal dUTP nick end labeling and flow-cytometric cell cycle analysis (sub-G1 formation). In humans in vivo, insulin secretory function was measured during hyperglycemic clamps in 65 normal glucose-tolerant subjects. We determined first and second phase of glucose-stimulated, glucagon-like peptide-1-stimulated, and arginine-stimulated insulin secretion. RESULTS: Adiponectin receptor-1 and -2 are expressed in human islets at the mRNA and protein level. Moreover, full-length adiponectin induces phosphorylation of acetyl coenzyme A carboxylase. However, adiponectin did not affect basal or glucose-stimulated insulin secretion or basal or fatty acid-induced beta-cell apoptosis. In vivo, fasting plasma adiponectin concentrations were not associated with glucose-stimulated first- and second-phase insulin secretion or with glucagon-like peptide-1- or arginine-stimulated insulin secretion (all P > 0.42). CONCLUSIONS: These data support a regulatory role of adiponectin in human islets; however, adiponectin does not seem to affect insulin secretion or basal/fatty acid-induced beta-cell apoptosis in humans.

Adiponectin↗
PubMed2005

Fatty acid-induced differential regulation of the genes encoding peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -1beta in human skeletal muscle cells that have been differentiated in vitro.

AIMS/HYPOTHESIS: The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) enhances metabolically relevant pathways, such as gluconeogenesis, fatty acid oxidation, thermogenesis, oxidative phosphorylation and mitochondrial biogenesis. Since regulation of the expression of the gene encoding PGC-1alpha (PPARGC1A) by nutrients/metabolites has not been assessed in detail, the aim of this study was to determine whether PPARGC1A (and PPARGC1B) expression is modulated by common plasma fatty acids in human skeletal muscle cells. METHODS: Human myotubes that had been differentiated in vitro were treated with 0.5 mmol/l myristate (C14:0), palmitate (C16:0), stearate (C18:0), palmitoleate (C16:1omega7), oleate (C18:1omega9) or linoleate (C18:2omega6). PPARGC1A/B mRNA was quantified by RT-PCR. Mitochondrial activity was determined by formazan formation. RESULTS: Untreated cells expressed 28-fold more PPARGC1B mRNA than PPARGC1A mRNA (13.33+/-2.86 vs 0.47+/-0.08 fg/mug total RNA, n=5). PPARGC1A expression was increased two- to three-fold by all unsaturated fatty acids (UFAs) tested (p<0.05 each, n=5). In contrast, saturated fatty acids (SFAs) did not modulate PPARGC1A expression. Furthermore, the effect of linoleate was not blunted by palmitate. PPARGC1B mRNA expression was not increased by either the UFAs or the SFAs. SFAs reduced PPARGC1B expression (p<0.05 for palmitate and stearate, n=5). Notably, linoleate reversed palmitate's repressive effect on PPARGC1B. Myotube mitochondrial activity was increased by all UFAs (p<0.01 each, n=5), but was impaired by the SFA stearate (p<0.001, n=5). CONCLUSIONS/INTERPRETATION: We report here that fatty acids differentially regulated expression of the genes encoding the PGC-1 isoforms. Since these effects were accompanied by significant changes in mitochondrial activity, we suggest that the fatty acid-induced regulation of expression of these genes plays an important role in muscle oxidative metabolism.

Carrier Proteins↗
PubMed2005

Insulin and its analogue glargine do not affect viability and proliferation of human coronary artery endothelial and smooth muscle cells.

AIMS/HYPOTHESIS: Present guidelines for the treatment of type 2 diabetes recommend HbA1c values of less than 7%. As beta cell function worsens during progress of the disease, insulin therapy is often necessary to achieve this ambitious goal. However, due to peripheral insulin resistance, many patients need rather high insulin dosages. In the light of the extremely high cardiovascular risk of diabetic patients, it is important to determine whether high concentrations of insulin or its frequently used analogues are harmful to the cardiovascular system. We therefore investigated the modulatory effects of regular human insulin and its analogue glargine on proliferation and apoptosis of human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (HCASMCs). METHODS: Cells were treated with regular human insulin or insulin glargine. Proliferation was determined by [3H]thymidine incorporation and by flow cytometric analysis of Ki-67 expression. Apoptosis was assessed by flow cytometry (cell cycle analysis and annexin V staining) and determination of caspase-3 activity. RESULTS: HCAECs and HCASMCs treated with regular human insulin or insulin glargine did not show significant increases in DNA synthesis or Ki-67 expression. Administration of regular human insulin or insulin glargine did not modulate the extent of apoptotic events. No influence of insulin on lipoapoptotic vascular cell death could be detected. CONCLUSIONS/INTERPRETATION: Taken together, neither regular human insulin nor insulin glargine influences growth and apoptosis of human coronary artery cells in vitro. Our data do not suggest that regular human insulin or insulin glargine promote atherosclerosis through mechanisms affecting the cellularity of human coronary arteries.

Apoptosis↗
PubMed2005

Adiponectin receptor gene expression in human skeletal muscle cells is not regulated by fibrates and thiazolidinediones.

BACKGROUND: Thiazolidinediones as PPARgamma agonists and fibrates as PPARalpha agonists improve insulin sensitivity in insulin-responsive tissues. Recent data show an induction of adiponectin receptor 2 (AdipoR2) by PPARalpha and PPARgamma agonists in human macrophages. OBJECTIVE: In this study, we examined the effects of thiazolidinediones and fibrates on the expression of adiponectin receptors in human skeletal muscle cells, an important cell type in the context of insulin resistance. RESULTS AND METHODS: In vitro differentiated human myotubes treated with troglitazone or rosiglitazone (20 h) showed no significant changes in AdipoR1 and AdipoR2 mRNA expression. PPARgamma activation was controlled by determination of PPARgamma mRNA induction. Likewise, differentiated myotubes treated with Wy-14,643 or fenofibrate (20 h) revealed no significant regulation of AdipoR1 and AdipoR2 mRNA. PPARalpha activation was assessed by measuring PDHK4 mRNA expression. CONCLUSION: Induction of AdipoR gene expression in human skeletal muscle cells is not involved in the insulin-sensitizing effects of thiazolidinediones or fibrates.

Adult↗
PubMed2005

Adipocytokines: fat-derived humoral mediators of metabolic homeostasis.

The metabolic syndrome currently reaches epidemic proportions in the Western industrialized world. Its hallmarks obesity, type 2 diabetes mellitus, and atherosclerosis are closely associated, and we are just beginning to understand the reasons for this relationship: adipose tissue-derived proteohormones (adipocytokines), under normal weight conditions, guarantee homeostasis of glucose and lipid metabolism, but their dysregulated production in the obese state promotes insulin resistance, inflammation, as well as atherosclerotic events. This review will focus on the current understanding of the adipocytokines' molecular role in metabolism and metabolic disease.

Adipocytes↗
PubMed2004

Association of the -514C-->T polymorphism in the hepatic lipase gene (LIPC) promoter with elevated fasting insulin concentrations, but not insulin resistance, in non-diabetic Germans.

Hepatic lipase hydrolyses triglycerides and phospholipids in all major classes of lipoproteins. The -514C-->T genetic variation in the hepatic lipase gene promoter was found to be associated with diminished lipase activity, dyslipidemia, and atherosclerosis. We investigated whether this polymorphism associates with hyperinsulinemia and insulin resistance in 535 normal glucose-tolerant Germans. Only in homozygous individuals (22 subjects), the T allele (frequency: 18.1 %) was significantly associated with elevated glucose concentrations after 120 min of oral glucose tolerance test (p = 0.05) and with elevated fasting concentrations of insulin (p = 0.03), triglycerides (p < 0.01), total and HDL-cholesterol (p = 0.02), as determined by multivariate linear regression analysis. In a recessive model (C/C+C/T vs. T/T), T/T was associated with decreased insulin sensitivity index (p = 0.03) as calculated from oral glucose tolerance test data (n = 535), but not with the glucose infusion rate during hyperinsulinemic euglycemic clamp (n = 218). In conclusion, we have provided evidence that, among the metabolic parameters tested, the hepatic lipase -514C-->T gene polymorphism correlates with elevated fasting insulin concentrations in a German population. Since no corresponding difference in insulin sensitivity was seen in the clamp-subgroup, an effect of this polymorphism on insulin clearance has to be considered.

Adult↗
PubMed2003

Induction of adiponectin gene expression in human myotubes by an adiponectin-containing HEK293 cell culture supernatant.

AIMS/HYPOTHESIS: Adiponectin, an adipocytokine known to be down-regulated in obesity-linked disorders, is considered to be a potential key mediator of insulin sensitivity. In this study, we asked whether adiponectin is able to regulate ten selected genes possibly associated with insulin sensitivity in human skeletal muscle cells. METHODS: To this end, we treated in vitro differentiated human myotubes with the culture supernatant of HEK293 cells stably transfected with human recombinant adiponectin and assessed gene expression by RT-PCR. Intracellular adiponectin protein was quantified by radioimmunoassay and visualized by Western blotting. RESULTS: In contrast to the control supernatant, the adiponectin-containing supernatant consistently induced expression of adiponectin mRNA in human myotubes from eight different donors (mean increase: 90-fold over control; n=8, p<0.001). This increase in mRNA was paralleled by a rise in intracellular adiponectin protein (mean increase: 8.3-fold over control; n=4, p<0.05). Expression of the other nine candidate genes was not altered. In human skin fibroblasts and HepG2 cells, the adiponectin-enriched supernatant did not induce relevant amounts of adiponectin mRNA. CONCLUSIONS/INTERPRETATION: In conclusion, we show here that adiponectin gene expression is specifically inducible in skeletal muscle cells.

Adiponectin↗
PubMed2003

Skeletal muscle cells from insulin-resistant (non-diabetic) individuals are susceptible to insulin desensitization by palmitate.

We recently demonstrated that in vivo insulin resistance is not retained in cultured skeletal muscle cells. In the present study, we tested the hypothesis that treating cultured skeletal muscle cells with fatty acids has an effect on insulin action which differs between insulin-sensitive and insulin-resistant subjects. Insulin effects were examined in myotubes from 8 normoglycemic non-obese insulin-resistant and 8 carefully matched insulin-sensitive subjects after preincubation with or without palmitate, linoleate, and 2-bromo-palmitate. Insulin-stimulated glycogen synthesis decreased by 27 +/- 5 % after palmitate treatment in myotubes from insulin-resistant, but not from insulin-sensitive subjects (1.50 +/- 0.08-fold over basal vs. 1.81 +/- 0.09-fold, p = 0.042). Despite this observation, we did not find any impairment in the PI 3-kinase/PKB/GSK-3 pathway. Furthermore, insulin action was not affected by linoleate and 2-bromo-palmitate. In conclusion, our data provide preliminary evidence that insulin resistance of skeletal muscle does not necessarily involve primary defects in insulin action, but could represent susceptibility to the desensitizing effect of fatty acids and possibly other environmental or adipose tissue-derived factors.

Adult↗
PubMed1998

The role of PDGF-dependent suppression of apoptosis in differentiating 3T3-L1 preadipocytes.

In a chemically defined serum-free culture system, platelet-derived growth factor (PDGF) as the only externally applied growth factor, in concert with corticosterone, 3-isobutyl-1-methylxanthine (IBMX) and low insulin (1nM), stimulates adipose conversion of 3T3-L1 preadipocytes. Omission of PDGF during the induction period results in loss of differentiation competence and apoptotic cell death. Induction of apoptosis is shown to be clearly mediated by PDGF withdrawal, since neither corticosterone nor IBMX affect the apoptotic behaviour of 3T3-L1 cells. Cell viability in the absence of the survival factor PDGF could be achieved by application of high insulin (1 microM) or ectopical expression of the anti-apoptotic proto-oncogene Bcl-2. However, PDGF-independent suppression of cell death does not trigger adipose conversion in the presence of corticosterone and IBMX. Therefore, we conclude that suppression of apoptosis per se is not permissive for differentiation of 3T3-L1 preadipocytes and PDGF might exert some additional differentiation-promoting effect(s).

3T3 Cells↗
PubMed1977

[The possible connection between the occurrence of embolism and thrombosis in the retinal vessels and the weather (author's transl)].

While in the comparatively short period of three months (middle Febraury to end of May 1976) embolisms and thromboses of the retinal vessels were suddenly observed much more commonly in the University Eye clinic in Münster we tried to discover a possible connection with the weather. All patients had conditions which predisposed to thrombo-embolic occlusive vascular disease. We use the decimal classification of weather, and on the basis of this we could prove a connection between the intensity of the start of the thromboembolic process and cyclonic and anticyclonic weather situations and situations which favour allergic-hyperergic reactions to inflammatory processes. In venous occlusion an increase in the impulse number in the area (0,02 V/m) and hence increased thrombocyte adhesion at the beginning of the thrombotic process seemed to be the deciding factor. We made comparisons with the literature. It seems to be ophthalmologically important that also increase in the light intensity can be associated with thrombo-embolic occlusions in the retinal vessels.

Adolescent↗