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H Hauner

Publications and source records attributed to H Hauner.

At least 91 records · Page 5Linked to original sources
PubMed1998

Tumor necrosis factor-alpha acutely inhibits insulin signaling in human adipocytes: implication of the p80 tumor necrosis factor receptor.

Tumor necrosis factor (TNF)-alpha is postulated to play a major role in the pathogenesis of obesity-linked insulin resistance, probably resulting from an interaction with insulin signaling pathways. This cross talk has now been investigated in human adipocytes at the level of phosphatidylinositol (PI) 3-kinase, and the TNF receptors (TNFRs) mediating these processes have been identified. Equilibrium binding studies using human adipocytes from mammary tissue indicated the presence of two populations of TNFR with apparent affinity constants of 13 pmol/l and 1.6 nmol/l, respectively. Interaction of TNF-alpha with insulin signaling was determined by quantification of insulin receptor substrate (IRS)-1-associated PI 3-kinase activity. Under control conditions, PI 3-kinase was activated about 10-fold in response to insulin (10[-7] mol/l, 5 min). Preincubation of adipocytes with 5 nmol/l TNF-alpha for 15 min resulted in a 60-70% reduction of insulin action, reaching a stable inhibition (40%) after longer incubation with the cytokine. The inhibitory action of TNF-alpha was dose-dependent, already detectable at 10 pmol/l, and was correlated to inhibition of tyrosine phosphorylation of IRS-1 with an unaltered autophosphorylation of the insulin receptor beta-subunit. The modulation of insulin signaling by TNF-alpha was found to be paralleled by a comparable inhibition of insulin-stimulated glucose transport. An agonistic TNFR1 antibody completely mimicked the inhibitory action of TNF-alpha on insulin signaling, whereas at 100 pmol/l TNF-alpha, a nonagonistic p80 TNFR antibody, was shown to ameliorate the inhibitory action of the cytokine. These findings indicate that in human adipocytes, low concentrations of TNF-alpha induce a rapid inhibition of insulin signaling at the level of PI 3-kinase. We suggest that under these conditions, the p80 TNFR is essential for initiating the intracellular cross talk that involves signaling by the p60 TNFR.

Adipocytes↗
PubMed1997

Contribution of androgens to the gender difference in leptin production in obese children and adolescents.

Recent studies demonstrated significantly higher serum leptin concentrations in females as compared with males, even after correction for differences in body fat mass. The aim of our study was to measure serum leptin concentrations in a large group of obese children and adolescents to determine the possible role of sex steroid hormones on both leptin serum concentrations and production in human adipocytes. Obese girls were found to have significantly higher leptin concentrations than boys at the same degree of adiposity (25.2+/-14.1 vs. 17.2+/-12.6 ng/ml, P < 0.001). In a multiple regression analysis with age and body mass index (percent body fat) as fixed variables, it turned out that testosterone had a potent negative effect on serum leptin in boys, but not in girls. In vitro experiments using newly developed human adipocytes in primary culture showed that both testosterone and its biologically active metabolite dihydrotestosterone are able to reduce leptin secretion into the culture medium by up to 62%. Using a semiquantitative reverse transcriptase-PCR method, testosterone was found to suppress leptin mRNA to a similar extent. These results suggest that, apart from differences in body fat mass, the higher androgen concentrations in obese boys are responsible for the lower leptin serum concentrations compared with obese girls.

Adipocytes↗
PubMed1997

[A cost of illness study of diabetes mellitus].

In a cost of illness study on the basis of data of a representative random sample of members of a Local Statuary Health Insurance (Allgemeine Ortskrankenkasse, AOK) treatment with anti-diabetics and the treatment controls in 1990 were recorded. The costs according to the type of diabetes treatment in 1990 were determined and compared with the estimated costs for treatment and therapy control corresponding to international standards. The random sample corresponds to the required standards in health economics of a population-related random sample, which is continually observed in the course of at least one year. The costs per diabetic patient were checked, as well as the costs which were shared by the insured community per 1,000 insured people for the treatment of their members affected with diabetes. Among 1,000 insured members there were 49 diabetes patients (standardised according to the age and sex distribution of the former West Germany). Of these 49 patients, 9 were insulin recipients, 25 were recipients of oral anti-diabetics, and 15 were diet-treated patients. Total costs amounted to DM 16,896/ 1,000 insured/ year. Of this total, DM 12,905 were accounted for by drug therapy and DM 3,991 by the therapy control. The estimates for a therapy corresponding to international standards in comparison to the applied therapy showed that a therapy following the recommendations would be 54% more expensive and therefore rise to DM 26,023/1,000 insured/year. A comparison of the therapy costs for the various diabetes groups shows that the costs for an insulin treated patient was roughly 6 times as high as for a patient treated orally and 30 times as high as for a diet-treated patient. However, applied to all diabetics in the insured community, a different relationship became apparent, depending on the prevalence of the diabetes sub-group. Only twice as much was expended for the insulin-treated patients (DM 11,074/1,000 insured/year) than for OAD recipients and diet treated patients put together (DM 5,822/1,000 insured/year). If the therapy corresponded to the minimal requirements of the recommendations, then the ratio of the estimated costs for the total of OAD and diet-treated patients (DM 10,031/1,000 insured/year) to insulin-treated patients (DM 15,992/1,000 insured/year) should be 1:1,5. It is emphasised that the costs of diet-treated patients rises relatively higher than those of the other two groups, because until now there has been no self control in this group.

Adult↗
PubMed1996

[Direct costs of ambulatory treatment of diabetes mellitus. Comparison of observed costs with estimated costs of adherence to the treatment standard].

BACKGROUND: The aim of this investigation was to record the observed direct costs of the outpatient treatment and therapy control of diabetic patients based on patient-related analysis of health care expenses in a population-based sample and to compare these costs with those generated if the minimum requirements of the European IDDM and NIDDM Policy Groups are fulfilled. Up to now there are only few studies on this topic. PATIENTS AND METHOD: Medical records of a 5% random sample of all insured members of the AOK Dortmund (n = 6085) in 1990 provided the data basis. The direct diabetes-specific therapy and care costs were compiled per patient and year. RESULTS: The annual costs for antidiabetic drugs, monitoring of blood glucose and glycated hemoglobin, test strips for self-monitoring, checking serum cholesterol, triglycerides and creatinine as well as for fundoscopy amounted to a mean of DM 1218.-per each insulin-treated patient (n = 65), DM 211.-per patient on oral antidiabetic drugs (OAD, n = 177), and DM 42.-per patient treated by diet alone (n = 108). Provided that the minimal recommendations of the European IDDM and NIDDM Policy Groups were followed the calculated costs would be DM 1758.-, DM 287.- and DM 198.-, respectively. CONCLUSION: Fulfilling the minimum standards for diabetes care of the European IDDM and NIDDM Policy Groups, respectively, would cause additional costs per patient and year of DM 540.-for insulin-treated. of DM 76.-for OAD-treated and of DM 156.-for patients treated by diet alone. On the other hand adherence to the recommendations would reduce the annual costs for oral antidiabetic drugs by 40%. Improved care of diabetic patients would result in significantly higher costs, but these extra expenses would be probably compensated by a reduction or delay of late complication.

Adult↗
PubMed1996

Biological effects of human growth hormone in rat adipocyte precursor cells and newly differentiated adipocytes in primary culture.

The effects of human growth hormone (hGH) on proliferation and differentiation of primary adipocyte precursor cells isolated from rat epididymal fat pads were studied under serum-free culture conditions. hGH markedly reduced the formation of new fat cells and the expression of glycerophosphate dehydrogenase activity, a marker enzyme of adipose differentiation, in a dose-dependent manner. To find an explanation for this inhibitory effect, we investigated the action of GH on (1) cell proliferation and on (2) lipid accumulation, the latter in the absence and presence of corticosterone. In undifferentiated cells, 5 nmol/L hGH increased both cell number and [3H]-thymidine incorporation (1.3- and 2.6-fold over basal, respectively). This effect was mediated by insulin-like growth factor-I (IGF-I), since hGH stimulated IGF-I production in undifferentiated cells by 12-fold and addition of an anti-IGF-I monoclonal antibody (IGF-I MAb) abolished the mitogenic effect of hGH but did not prevent hGH-induced suppression of adipose differentiation. In developing fat cells, hGH significantly reduced cellular 2-deoxyglucose uptake and glucose incorporation into lipids. In addition, hGH exhibited a lipolytic action in the presence of insulin and triiodothyronine. These effects were not prevented by IGF-I MAb. Specific binding of [125I]-hGH to precursor cells increased significantly during adipose conversion. In differentiated cells Scatchard analysis yielded linear plots with an apparent Kd of 0.16 nmol/L and 8,400 sites per cell. Taken together, these data show that hGH reduces adipose conversion in primary cultures of rat adipocyte precursor cells while promoting cell proliferation through an increase in IGF-I production.

Adipocytes↗
PubMed1996

Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors.

In a cross-sectional study the frequency of insulin-induced lipohypertrophy at injection sites was assessed in 223 type 1 and 56 type 2 diabetic patients. 64 (28.7%) of the subjects with type 1 diabetes, but only 2 (3.6%) of those with type 2 diabetes presented clinical evidence of lipohypertrophy. In every second affected type 1 diabetic patient lipohypertrophy developed within 2 years after starting insulin therapy. The occurrence of lipohypertrophy was independent of the insulin source and mode of therapy. In a multivariate logistic regression analysis young age, low body mass index, abdominal injection site and, particularly, missing rotation of injection site were significant independent risk factors for the presence of insulin-induced lipohypertrophy. Avoidance of such areas led to a partial or full remission of tissue swellings in 6 of 11 cases under observation for one year. In conclusion, lipohypertrophy is still a frequent complication of insulin therapy. To prevent such local skin reactions insulin-treated patients should be more intensively trained to regularly change injection sites.

Adult↗
PubMed1996

Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans.

Differences in fat cell size and function among adipose tissue depots are well known and may be important in the pathophysiology of the metabolic and cardiovascular complications of obesity. Since the newly discovered adipocyte hormone leptin is thought to be a central factor in the regulation of energy homeostasis, it may be interesting to know if there are regional differences in leptin production. The aim of this study was to compare the level of leptin expression in the omental and subcutaneous abdominal adipose tissue from obese humans. Adipose tissue samples were collected from 25 severely obese adults (mean BMI: 48.9 +/- 9.7 kg/m2) undergoing vertical gastric banding. Semi-quantitative determination of leptin mRNA by the RT-PCR technique showed significantly lower leptin expression in omental compared to subcutaneous abdominal adipose tissue (leptin/Sp1 ratio in omental vs. subcutaneous fat: 1.53 +/- 0.89 vs. 3.02 +/- 1.58, p < 0.01). Identical results were obtained when Northern blotting was applied in a subgroup. Leptin expression increased with age in omental adipose tissue (r = 0.42, p < 0.05), but not in subcutaneous tissue. No correlation was found between BMI or waist/hip ratio (WHR) and leptin expression in omental or subcutaneous adipose tissue. The regional difference in leptin expression was similar in the patients with impaired glucose tolerance/type-2 diabetes and those with normal glucose tolerance. In conclusion, the results of this study indicate that leptin expression is lower in omental than subcutaneous adipose tissue, possibly due to differences in fat cell size and/or sympathetic innervation.

Abdomen↗
PubMed1996

Relationship between replication and differentiation in cultured human adipocyte precursor cells.

The aim of this study was to investigate the role of cell replication for the differentiation of human adipocyte precursor cells in primary culture. When cells were seeded in a medium supplemented with 10% fetal bovine serum, they started to proliferate within 48 h after exposure, as assessed by cell counting and [3H]thymidine autoradiography. When cells were inoculated in the absence of serum, a significant degree of cell proliferation was not detectable. Histochemical investigations using bromodeoxyuridine incorporation demonstrated that cells replicating their DNA did not accumulate lipid droplets. Inoculating adipocyte precursor cells under completely serum-free conditions resulted in a 30-50% higher expression of lipogenic enzymes such as glycerol-3-phosphate dehydrogenase and lipoprotein lipase than keeping cells in serum-supplemented medium for the initial 16 h. Addition of cytosine arabinoside at concentrations that effectively block mitosis did not interfere with adipocyte development. In conclusion, adipocyte precursor cells from human adipose tissue do not require cell division to enter the differentiation process in vitro. These cells may have already undergone possibly critical cell divisions in vivo and may be in a late stage of adipocyte development.

Adipocytes↗
PubMed1996

Mitogenic and antiadipogenic properties of human growth hormone in differentiating human adipocyte precursor cells in primary culture.

Children with GH deficiency have enlarged fat cells but a reduced number of fat cells compared with healthy children. After treatment with human GH (hGH) both fat cell volume and number are shifted toward normal. To clarify the role of hGH in fat cell formation in human adipose tissue, we investigated the effect of hGH on the proliferation and the differentiation of cultured human adipocyte precursor cells obtained from five children and 10 adults. In a chemically defined serum-free medium treatment of adipocyte precursor cells with hGH led to an increase in IGF-I production and a stimulation of cell proliferation, which could be blocked by a MAb raised against human IGF-I. hGH dose-dependently reduced the number of differentiating cells and suppressed the expression of glycerol-3-phosphate dehydrogenase (GPDH), a marker of adipose differentiation. No significant differences in the hGH effects on proliferation and differentiation capacities were seen between cultures obtained from children and adults. In newly differentiated adipocytes, hGH inhibited glucose uptake and lipogenesis, and stimulated lipolysis. Scatchard analysis of hGH competition experiments using 125I-labeled hGH yielded a linear plot with an apparent Kd of 1.08 nM and an estimated number of 7000 hGH receptors per cell. These data suggest that hGH is able to enlarge the human adipocyte precursor pool via induction of IGF-I synthesis but exhibits a direct antiadipogenic activity. hGH is also able to reduce fat cell volume by reducing lipogenesis and increasing lipolysis.

Adipocytes↗
PubMed1996

Insulin and cortisol promote leptin production in cultured human fat cells.

The aim of this study was to investigate the regulation of leptin expression and production in cultured human adipocytes using the model of in vitro differentiated human adipocytes. Freshly isolated human preadipocytes did not exhibit significant leptin mRNA and protein levels as assessed by reverse transcriptase (RT)-polymerase chain reaction (PCR) and radioimmunoassay (RIA). However, during differentiation induced by a defined adipogenic serum-free medium, cellular leptin mRNA and leptin protein released into the medium increased considerably in accordance with the cellular lipid accumulation. In fully differentiated human fat cells, insulin provoked a dose-dependent rise in leptin protein. Cortisol at a near physiological concentration of 10(-8) mol/l was found to potentiate this insulin effect by almost threefold. Removal of insulin and cortisol, respectively, was followed by a rapid decrease in leptin expression, which was reversible after readdition of the hormones. These results clearly indicate that both insulin and cortisol are potent and possibly physiological regulators of leptin expression in human adipose tissue.

Adipose Tissue↗
PubMed1996

[Obesity].

Explore the source record for details and available documents.

Adult↗
PubMed1996

Frequency of 'obesity' in medical records and utilization of out-patient health care by 'obese' subjects in Germany. An analysis of health insurance data.

OBJECTIVE: The aim of this study was to assess the frequency of the diagnoses 'overweight' or 'obesity' in medical records and to examine the utilization of the out-patient health care system by 'obese' subjects. DESIGN: All claims-cards, prescriptions and other diagnosis-carrying medical certificates from 1990 of a representative sample of members of a large local health insurance were collected and analyzed anonymously in a patient-related approach. SUBJECTS: A 5% random sample (n = 6085) of all members of the general local health insurance (AOK) in the city of Dortmund, Germany. MEASUREMENTS: The percentage of subjects carrying the diagnosis of 'overweight' and/or 'obesity' was determined. In addition, the utilization of medical services and the presence of comorbid conditions in the documents of the AOK was recorded. RESULTS: A total number of 377 'obese' subjects was identified corresponding with a prevalence rate of 6.2%. Among those, more women than men carried one of these diagnoses (240 vs 137, 7.3% vs 4.9%, p < 0.01). In comparison with an age- and sex-matched control group (n = 1131) the 'obese' subjects had significantly more practice contacts (25.7 vs 17.5/year, p < 0.01) and received more medical services (64.2 vs 43.0/year, p < 0.01), including more prescriptions (20.9 vs 15.5/year, p < 0.01). Furthermore, the 'obese' subjects had more additional diagnoses indicating a higher comorbidity and received more drugs for diseases and complications which are characteristic of obesity but also for other diseases. CONCLUSION: This data suggests that in view of its high prevalence in Germany obesity is perceived and documented by health professionals only in a minority of affected subjects indicating that this disorder is considerably under-estimated. It is also evident from the data that obesity is mainly noticed in those who have other serious health problems.

Adolescent↗
PubMed1995

Effects of tumour necrosis factor alpha (TNF alpha) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture.

Tumour necrosis factor alpha (TNF alpha) has been found to cause a delipidation of fat cells and a decrease of the adipose tissue mass. In the present study, we tried to elucidate some of the mechanisms responsible for this phenomenon by investigating the action of TNF alpha on specific pathways which are involved in lipid storage. Cultured stromal cells from human adipose tissue were induced to differentiate into adipose cells by exposure to adipogenic factors and subsequently used for studying the effects of TNF alpha on fat cell metabolism. Presence of 5 nmol/l TNF alpha for 24 h resulted in a complete loss of the stimulatory effect of insulin on 2-deoxy-glucose transport. This inhibitory action was paralleled by a decrease of GLUT4 protein and mRNA levels. The amount of cellular GLUT4 protein was reduced by 49 +/- 3% after a 24-h exposure and by 82 +/- 18% after a 72-h exposure to 5 nmol/l TNF alpha. GLUT4 mRNA was almost undetectable after a 24-h incubation with 5 nmol/l TNF alpha. In a similar time-dependent manner, TNF alpha dramatically reduced the lipoprotein lipase mRNA content of the cells. Furthermore, incubation of cultured human fat cells with TNF alpha resulted in a marked dose-dependent stimulation of lipolysis, assessed by glycerol release, by up to 400% above controls, which became apparent after a 6-h exposure at the earliest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

The role of growth hormone/insulin-like growth factors in adipocyte differentiation.

Growth of the adipose tissue results from both the enlargement of mature adipocytes and the formation of new adipocytes from adipocyte precursor cells. The differentiation process of adipocyte precursor cells is controlled by a variety of hormones. Clinical observations indicate that growth hormone (GH) and insulin-like growth factor I (IGF-I) are able to influence the growth of the adipose organ. Recent in vitro studies using cultures of clonal and primary adipocyte precursor cells have elucidated the role of GH and IGF-I in adipocyte differentiation. From the studies it can be concluded that GH is able to enlarge the pool of adipocyte precursor cells capable of differentiating into mature adipocytes, which occurs under the control of other adipogenic hormones. However, due to its metabolic action, GH is also able to reduce the volume of mature adipocytes and thus the net result of its biological action is aimed at reducing body fat. IGF-I stimulates the differentiation process by inducing critical cell divisions of adipocyte precursor cells necessary for their differentiation. IGF-I, which is known to be regulated by GH and several nutritional factors, may exert its effects in the adipose tissue in an autocrine/paracrine and endocrine way. This review summarizes the results of recent studies investigating the role of GH and IGF-I in adipocyte differentiation.

Adipocytes↗
PubMed1995

Effects of epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) on human adipocyte development and function.

We investigated the effects of epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) on the differentiation of human adipocyte precursor cells and some metabolic aspects of newly formed fat cells kept in primary culture. Exposure of stromal cells from human adipose tissue to EGF (0.01-100 ng mL-1) resulted in a dose- and time-dependent decrease in the number of developing fat cells and the activity of glycerol-3-phosphate dehydrogenase (GPDH), a marker of adipose differentiation. Continuous presence of EGF completely blocked lipid accumulation with a ED50 in the range of 0.2 ng mL-1. This inhibitory action of EGF was associated with a potent stimulation of cell proliferation, up to 8-fold compared with cultures in the absence of EGF. PDGF (0.1-50 ng mL-1) and FGF (0.1-100 ng mL-1) provoked a less marked suppression of GPDH activities which was significant at concentrations of 10 ng mL-1 and higher. A 12 day exposure to EGF of differentiated cells was followed by a suppression of GPDH and, again, a significant increase in cell number. Concomitantly, a distinct loss of cellular lipids was observed in the newly formed adipocytes. This effect could be partly explained by a stimulation of lipolysis, since EGF caused an increase of glycerol in the culture medium. Addition of PDGF or FGF to newly developed fat cells had no effect on lipolysis but, at higher concentrations, also decreased GPDH activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗