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Biomedical subjects

K Kristensen

Publications and source records attributed to K Kristensen.

At least 19 recordsLinked to original sources
PubMed2005

Increased adiposity and reduced adipose tissue mRNA expression of uncoupling protein-2 in first-degree relatives of type 2 diabetic patients: evidence for insulin stimulation of UCP-2 and UCP-3 gene expression in adipose tissue.

The mitochondrial uncoupling proteins (UCP-2 and UCP-3), which have been suggested to be involved in the development of obesity by controlling the energy expenditure (EE), were studied in 22 healthy first-degree relatives (FDRs) of patients with type 2 diabetes and 13 body mass index (BMI)- and age-matched healthy control subjects. Abdominal subcutaneous adipose tissue biopsies were obtained before and after 150-min hyperinsulinaemic clamp (average serum insulin 250 pM). Basal adipose tissue UCP-2 mRNA levels in the FDR group were significantly lower than that in the control group. After the hyperinsulinaemic clamp, adipose tissue UCP-2 mRNA levels were increased by 32% in the control group (p < 0.05) and 32% in the FDR group (p < 0.05). The basal adipose tissue UCP-3 mRNA level was similar in the two groups and increased in both the groups during hyperinsulinaemia (p < 0.001). Dual energy X-ray absorptiometry showed that despite similar BMI the FDR group had significantly higher fat mass (FM) per cent compared to that of the control group (p < 0.01). The UCP-2 mRNA expression was inversely correlated with the amount of adipose tissue (r = -0.53, p < 0.001), and multiple regression analysis revealed that only the amount of FM was independently correlated with basal UCP-2 mRNA levels, whereas age, gender nor family history of type 2 diabetes contributed independently to the variation in UCP-2 mRNA levels. No differences in EE were observed between the two groups, and no association between EE and UCP mRNA expression was found. In conclusion, we have demonstrated that adipose tissue UCP-2 and UCP-3 mRNA levels are significantly increased during a 150-min hyperinsulinaemic clamp. The UCP-2 mRNA levels were expressed at a significantly lower level FDR to type 2 diabetes compared to control subjects. However, in multiple regression analysis controlling for amount of adipose tissue, the difference between the two groups disappeared. Thus, only the amount of adipose tissue contributed independently to the variation in UCP-2 mRNA expression.

Adipose Tissue↗
PubMed2005

Further delineation of the 22q13 deletion syndrome.

A chromosomal deletion syndrome associated with a 22q13 microdeletion has previously been reported in approximately 75 children. We report six cases from Denmark with a deletion of 22q13. One was cytogenetically visible by conventional karyotyping, one was diagnosed by high resolution karyotyping after the demonstration of low arylsulfatase A activity. Two were diagnosed by high resolution CGH analysis, one was diagnosed by multisubtelomeric FISH analysis and one was diagnosed serendipitously as lack of the control signal in a FISH analysis for 22q11 deletion. One of the cases was a mosaic with 16% of cells showing two signals. The phenotype of the children included: generalized developmental delay, compromised language development, hypotonia, normal or accelerated growth and minor facial dysmorphism. Other features were partial agenesis of the corpus callosum, bilateral ureteropelvic stricture, gastroesophageal reflux and hearing loss. One case had a different phenotype, and showed a deletion as well as a duplication. The extent of the deletion was studied by quantitative PCR analysis of a number of DNA markers in the 22q13 region. The deletions varied in size, extending from 4.0 to 9.0 Mb. The clinical phenotype seemed rather similar although some specific features might be attributable to differences in deletions.

Abnormalities, Multiple↗
PubMed2003

Rehospitalization for respiratory syncytial virus infection in infants with extremely low gestational age or birthweight in Denmark.

AIM: To determine the risk of rehospitalization for respiratory syncytial virus (RSV) infection during the first 2 y of life in extremely preterm infants. METHODS: Records on all rehospitalizations during the first 2 living years of all infants born with gestational age <28 wk or birthweight <1,000g during 1994 and 1995 in Denmark were retrospectively reviewed. RESULTS: Among 240 eligible infants, 43 (18%) had been rehospitalized 48 times owing to RSV. In infants (n = 210) without CLD the risk of rehospitalization for RSV was 16%, whereas in infants with CLD (n = 30) it was 30% (p = 0.065). Eighteen infants (38%) required respiratory support (supplemental oxygen only 3, continuous positive airway pressure 14, mechanical ventilation 1). Apart from CLD the only factor that could be associated with increased risk of hospitalization for RSV was discharge during autumn (p = 0.05). No infant died from RSV infection. CONCLUSION: The high rate of rehospitalization for RSV in extremely preterm infants in Denmark, especially in infants with CLD, should lead to considerations concerning more widespread use of prophylaxis against RSV in these infants.

Denmark↗
PubMed2001

Regulation of UCP1, UCP2, and UCP3 mRNA expression in brown adipose tissue, white adipose tissue, and skeletal muscle in rats by estrogen.

The effects of ovariectomy (OVX) and estrogen substitution on body weight, body composition, food intake, weight gain, and expression of uncoupling proteins (UCPs) in brown adipose tissue (BAT), white adipose tissue (WAT), and skeletal muscle were studied in four groups of rats: (1) Sham-operated rats (N = 8), (2) ovariectomized rats (OVX - E) (N = 8), (3) estrogen-treated OVX rats (OVX + E) (N = 8), and (4) OVX rats on energy restriction (OVX - E + D) (N = 8). OVX was associated with an increase in food intake and body weight gain during a 5-week study period compared to sham-operated rats. The estrogen-substituted rats had a significantly lower food intake and weight gain during the 5 weeks compared to the sham-operated group. However, we also included a nontreated OVX group that was allowed to eat only enough chow to match the weight gain of the sham-operated group. To match the weight gain in the two groups, the OVX group had to consume 16% less chow than the sham-operated group. In BAT, the UCP1 expression was significantly lower in estrogen-deficient rats compared to either intact rats or estrogen-substituted rats, whereas UCP2 and UCP3 mRNA expression was similar in BAT from all four groups. In WAT, both estrogen-deficient groups had significantly lower UCP2 mRNA expression compared to the control rats and estrogen-treated rats; In contrast, the UCP3 mRNA expression in WAT was similar in all four groups. Finally, in skeletal muscle the OVX group on mild energy restriction had reduced UCP3 mRNA expression compared to control, OVX, and estrogen-treated rats. In contrast, the UCP2 mRNA expression in skeletal muscle was similar in all four groups. Thus, the findings that estrogen deficiency is followed by reduced UCP1 expression in BAT and reduced UCP2 expression in WAT in association with weight gain probably caused by a decrease in energy expenditure might indicate that UCPs play a role for the estrogen-mediated changes in body weight and energy expenditure.

Adipose Tissue↗
PubMed2001

Demonstration of estrogen receptor subtypes alpha and beta in human adipose tissue: influences of adipose cell differentiation and fat depot localization.

A novel ER-subtype, the ER-beta has recently been characterized in various tissues, furthermore five isoforms of the ER-beta are known (ER-beta1--ER-beta5). Using immunoblotting and real- time RT-PCR, ER-alpha and beta were studied in human adipose tissue. The expression of ER-alpha mRNA was equal in subcutaneous gluteal adipose tissue, subcutaneous abdominal and intra-abdominal adipose tissue, similar findings were obtained at the protein level. In contrast the amount of ER-beta1 (protein and mRNA) was significantly lower in intra-abdominal adipose tissue as compared with the subcutaneous adipose tissue (five-fold lower in women, P<0.005 and three-fold lower in men, P<0.005) whereas the expression of ER-beta4 and -beta5 mRNA isoforms were significantly higher in gluteal adipose tissue compared to subcutaneous abdominal adipose tissue. No significant gender differences in ER expression was detected in any of the fat depots investigated. During adipocyte differentiation the expression of ER-alpha, -beta4 and -beta5 mRNA declined, whereas, the expression of ER-beta1 mRNA was constant. In conclusion, the existence of ER-beta isoforms in human adipose tissue was demonstrated and the amount of these receptors was dependent upon fat depot localization, with much reduced expression of ER-beta1 in intra-abdominal adipose tissue compared to subcutaneous adipose tissue. These findings may indicate that estrogens could have differentiation and depot specific effects in human adipose tissue.

Abdomen↗
PubMed2001

Gene expression of a truncated and the full-length growth hormone (GH) receptor in subcutaneous fat and skeletal muscle in GH-deficient adults: impact of GH treatment.

In humans at least two GH receptors are significantly expressed. One is the full-length receptor (GHR); the other is a truncated form (GHRtr), that lacks most of the intracellular domain. This receptor may inhibit the action of the full-length receptor. Circulating GH-binding protein (GHBP) is a proteolytically cleaved product from both of these receptors. The clinical relevance of the different receptor types is unknown. We examined the gene expression of GHR and GHRtr in human adipose tissue and skeletal muscle and the influence of GH treatment on this expression. Furthermore, we studied the relationship of circulating GHBP and body composition to GHR and GHRtr gene expression. Eleven adult GH-deficient patients were studied before and after 4 months of GH substitution therapy. Abdominal fat obtained by liposuction and femoral muscle biopsies were taken at baseline and after 4 months. Gene expression of GHR and GHRtr in adipose tissue and skeletal muscle was determined and expressed relative to the expression of beta-actin. Gene expression of GHR in abdominal sc adipose tissue was not altered, whereas the expression of GHRtr increased significantly. In skeletal muscle inverse changes were seen in the expression of messenger ribonucleic acid (mRNA) levels for the two GH receptor forms: expression of GHR increased significantly, whereas mRNA levels for GHRtr decreased. As expected, body composition changed with reduction of body fat mass after 4 months of GH treatment. Levels of circulating GHBP decreased significantly. We conclude that GH treatment in GH-deficient adults changes the expression of mRNA for GHR and GHRtr in adipose tissue and skeletal muscle. Whether these changes are responsible for the observed changes in body composition in response to GH treatment and the observed changes in levels of circulating GHBP, however, needs further elucidation.

Adipose Tissue↗
PubMed2000

Systemic administration of epidermal growth factor increases UCP3 mRNA levels in skeletal muscle and adipose tissue in rats.

We have previously reported that systemic epidermal growth factor (EGF) treatment in rats reduces the amount of adipose tissue despite an unaltered food intake. The mitochondrial uncoupling proteins (UCP2 and UCP3) are thought to uncouple the respiratory chain and thus to increase energy expenditure. In order to find out whether the UCP system was involved in the EGF-induced weight loss, the effects of EGF on UCP2 and UCP3 in adipose tissue and skeletal muscle were investigated in the present study. Eight rats were treated with placebo or EGF (150 microg/kg/day) for seven days via mini-osmotic pumps. The EGF-treated rats gained significantly less body weight during the study period than the placebo-treated animals and had significantly less adipose tissue despite a similar food intake. The placebo group and the EGF group had similar UCP2 mRNA expression (in both adipose tissue and skeletal muscle), whereas the EGF-treated group compared to the placebo group had significantly higher UCP3 mRNA expression in both skeletal muscle (3.76 +/- 0.90 vs 8.41 +/- 0.87, P < 0.05) and in adipose tissue (6.38 +/- 0.71 vs 12.48 +/- 1.79, P < 0.05). In vitro studies with adipose tissue fragments indicated that the EGF effect probably is mediated indirectly as incubations with EGF (10 microM) were unable to affect adipose tissue UCP expression, whereas incubations with bromopalmitate stimulated both UCP2 and UCP3 mRNA expression twofold. Thus, EGF treatment in vivo was found to enhance UCP3 mRNA expression in both adipose tissue and skeletal muscle, which may indicate that the EGF effect on body composition might involve up-regulation of UCP3 in skeletal muscle and adipose tissue.

Adipose Tissue↗
PubMed2000

Regulation of uncoupling protein (UCP) 2 and 3 in adipose and muscle tissue by fasting and growth hormone treatment in obese humans.

OBJECTIVE: To investigate whether the expression of uncoupling proteins (UCP2 and UCP3) was affected by a very low calorie diet (VLCD) and growth hormone (GH) treatment for 4 weeks. DESIGN: A randomized, placebo-controlled intervention study of VLCD with or without concomitant GH-treatment. SUBJECTS: Seventeen obese women (body mass index, BMI=42.1+/-1.4 kg/m2 (range 31.8-54.5 kg/m2)) treated with VLCD for 4 weeks and randomized to concomitant placebo treatment (n=9) or GH treatment (n=8). MEASUREMENTS: Fat mass and lean body mass were measured by dual-energy X-ray absorptiometry. Energy expenditure (EE) was measured by indirect calorimetry. UCP2 and UCP3 mRNA were measured in adipose tissue and skeletal muscle biopsies before VLCD and after VLCD+/-GH-treatment by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: VLCD treatment resulted in a mean weight loss of 5.23 kg+/-0.8 (P<0.01), a 4.1% decrease in EE (P<0.05) and a 24% decrease in UCP3 mRNA in adipose tissue (P<0.03), whereas adipose tissue UCP2 mRNA and skeletal muscle UCP2 and UCP3 mRNA levels were unchanged. GH-treatment had no effects on EE, changes in body weight or UCP mRNA level. In multiple regression analysis the change in EE caused by VLCD was significantly correlated with changes in adipose tissue UCP2 mRNA (r=0.66, P<0.02) and a tendency towards a significant association with the change in adipose tissue UCP3 mRNA (r=0.45, P=0.09), but not with change in body weight, skeletal muscle UCP2 or UCP3 mRNA levels. CONCLUSION: VLCD for 4 weeks decreased UCP3 mRNA expression in human adipose tissue, whereas GH-treatment had no effect on UCP expression. Multiple regression analysis demonstrated that changes in adipose tissue UCP2 and probably UCP3 mRNA were correlated with the change in EE. These findings indicate that UCPs in adipose tissue in very obese individuals might play a role for the reduction in EE observed during energy restriction.

Absorptiometry, Photon↗
PubMed2000

Interactions between sex steroid hormones and leptin in women. Studies in vivo and in vitro.

OBJECTIVE: To investigate the associations between sex hormones and leptin. In addition, to investigate the direct effect of sex hormones by incubations of human subcutaneous adipose tissue explants, in vitro. DESIGN: Cross-sectional study and an experimental in vitro study. SUBJECTS: 36 women (age, 23-65 y; body mass index, BMI, 19-65 kg/m2) participated in the cross-sectional study. Subcutaneous abdominal biopsies were taken from nine women (age, 28 - 46 y; BMI, 25.5-36.0 kg/m2) for the in vitro study. MEASUREMENTS: Fat distribution parameters (by dual-energy X-ray absorptiometry and anthropometry), sex hormones, leptin and insulin. RESULTS: Leptin correlated significantly with most estimates of adipose tissue mass (r= 0.5 - 0.9, P< 0.05). However, when the study group was divided in three equal groups (non-obese, obese, and very-obese) it revealed that the correlation predominantly was found in non-obese. In simple correlation analysis leptin was significantly associated with estimates of adipose tissue, insulin and several sex hormones. However, in multiple regression analysis only insulin (partial correlation coefficient = 0.55, P < 0.004) and percentage fat mass (partial correlation coefficient = 0.72, P<0.001) were significantly and independently correlated with leptin without any independent effect of sex hormones. These findings were in agreement with the in vitro studies where neither estrogen nor androgens (testosterone or DHT) affected subcutaneous adipose tissue leptin production. Dexamethasone (10nM) stimulated adipose tissue leptin production 3-fold (P < 0.001). CONCLUSION: In regression analysis, where both insulin and measurements of fat mass were taken into account, androgens or estrogens did not independently contribute to the variation in leptin levels. Estrogens and androgens had no direct effects on adipose tissue leptin production in vitro. Thus, the sexual dimorphism evident in serum leptin is not likely to be due to a direct influence of sex hormones on leptin production in females.

Absorptiometry, Photon↗
PubMed2000

Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients.

It is well known that growth hormone (GH) treatment reduces fat mass (FM), which presumably is mediated through stimulation of triglyceride breakdown and inhibition of adipose tissue lipoprotein lipase activity (AT-LPL). However, it is unknown which of the 2 GH-regulated pathways are of most importance for the reduction in FM. We investigated the effect of weight loss together with GH treatment on the activity and gene expression of LPL and hormone-sensitive lipase (HSL) in AT and muscle tissue. A very-low-calorie diet ([VLCD] 740 kcal/d) was given to 18 obese women (body mass index [BMI] > 35 kg/m2) and half of them were treated with GH (0.04 IU/kg) for 4 weeks in a randomized double-blind placebo-controlled study. Subcutaneous fat and muscle biopsies were taken before and after 4 weeks. Weight loss after 4 weeks was similar in the 2 groups, with a reduction of 4.5% (placebo) and 4.6% (GH) and a reduction of FM by 7.4% and 9.0% ([NS] nonsignificant). The weight loss resulted in a small and NS reduction of AT-LPL activity by 20% +/- 12% in the placebo group, but in the GH group, AT-LPL was significantly reduced by 65% +/- 8% (P < .01). Muscle LPL (M-LPL) activity was not affected by the weight loss alone, but a significant reduction was observed in the GH group (20.4% +/- 10%, P < .05). AT-HSL activity was significantly enhanced after weight loss, but GH had no additional effect on this minor increment. This is in accordance with the finding that the increment in free fatty acid (FFA) after weight loss was similar in the 2 groups. GH treatment was associated with a significant reduction of high-density lipoprotein (HDL) cholesterol (P < .05). In conclusion, GH significantly inhibited AT-LPL activity but had no additional effect on the hypocaloric-induced loss of FM, indicating that under such circumstances, AT-LPL does not directly regulate adipose tissue mass. GH was not found to have opposite effects on the activity of LPL in adipose tissue and muscle, since GH treatment reduced them both (by 65% and 20%, respectively). The VLCD-induced weight loss was associated with a minor enhanced activity of AT-HSL with no independent effect of GH. Thus, concerning body weight, FM, and lipolytic activity, treatment with GH offers no extra benefits during a VLCD for 4 weeks.

Adipose Tissue↗
PubMed2000

Erythrocyte-methotrexate and disease activity in children treated with oral methotrexate for juvenile chronic arthritis.

The concentration of methotrexate (MTX) in erythrocytes (E-MTX) was measured twice with three months interval in 21 children suffering from juvenile chronic arthritis (JCA). At the same time joint score, visual analogue scale (VAS), and laboratory parameters (CRP, WBC, PMNs, and ALAT) were obtained. There was only a weak insignificant correlation between the dose of MTX/m2 and E-MTX (r=0.24, p=0.11). No significant relations between the clinical or laboratory parameters and E-MTX was found. However, ALAT above normal range was associated with a lower dose of MTX (p=0.02) and lower VAS (p=0.02), indicating that toxicity may be associated with less articular discomfort. At present we consider routine determination of E-MTX in children with JCA of limited value.

Administration, Oral↗
PubMed2000

Increased body fat mass and suppression of circulating leptin levels in response to hypersecretion of epinephrine in phenylethanolamine-N-methyltransferase (PNMT)-overexpressing mice.

Epinephrine is a major stress hormone that plays a central role in the control of metabolic function and energy homeostasis. To evaluate the role of epinephrine and the physiological and pathophysiological consequences of sustained elevation of epinephrine on metabolic and endocrine function, we studied several metabolic parameters and circulating leptin levels in a newly developed transgenic mouse model of phenylethanolamine-N-methyltransferase (PNMT) overexpression. A 100-fold overexpression of PNMT and subsequent elevation of epinephrine levels resulted in a marked suppression of circulating leptin levels in the transgenic animals (1.14 +/- 0.05 vs. 2.17 +/- 0.35 ng/ml; P < 0.01), which correlated negatively with plasma epinephrine (r = -0.82; P < 0.05), thus providing evidence for an inhibitory action of epinephrine on leptin production in vivo. In parallel, we found a marked increase in the body fat content of the transgenic animals (12.54 +/- 1.5 vs. 6.22 +/- 0.2%; P < 0.01) that was accompanied by enlarged adipocytes, indicating an increased lipid storage in PNMT transgenic mice. Interestingly, however, transgenic animals had normal body weight and did not exhibit major alterations in carbohydrate metabolism, as evidenced by analysis of random and fasted blood glucose levels, plasma insulin and C peptide levels, and insulin tolerance test. The metabolic alterations observed were not secondary to changes in food intake or increased activity of the hypothalamic-pituitary-adrenal axis, as there were no differences in these parameters. In summary, sustained primary overproduction of epinephrine resulted in suppression of plasma leptin levels and increased lipid storage in the PNMT transgenic mice. The concerted action of the sympathoadrenal system and reduced leptin may contribute to defending energy reservoirs while maintaining a normal body weight, which may be of vital importance under conditions of stress and energy deficiency.

Adipose Tissue↗
PubMed1999

Regulation of leptin by steroid hormones in rat adipose tissue.

We investigated if steroid hormones regulate the secretion and the expression of leptin in female and male rat adipose tissue fragments in vitro. Dexamethasone time and dose-dependently increased the secretion and mRNA expression of leptin with a half-maximal stimulation of approximately 1 nM. A time-course revealed a maximal stimulatory effect of 17 beta-estradiol after 24 hours. In male adipose tissue 17 beta-estradiol increased leptin secretion (32% by 50 nM 17 beta-estradiol, P = 0.07 and 34% by 500 nM 17 beta-estradiol, P < 1780.05) after 24 hours. An additional effect of estrogen was seen in the dexamethasone (50 nM) stimulated cells (38% with 50 nM 17 beta-estradiol, P < 0.05 and 48% by 500 nM 17 beta-estradiol, P < 0.05). Basal secretion of leptin was equal in female and male adipose tissue, whereas the effects of 17 beta-estradiol (50 nM) and dexamethasone were significantly increased in female as compared with male adipose tissue. Progesterone, testosterone, dihydrotestosterone and dehydroepiandrostendione-sulfate neither affected leptin secretion in male nor female adipose tissue in vitro. Furthermore, to investigate the effect of estrogen female rats were ovariectomized (OVX) and the adipose tissue was incubated in vitro and compared with adipose tissue leptin secretion from sham operated rats (SHAM), and with ovariectomized rats treated with 17 beta-estradiol (EST). A decreased basal and dexamethasone-stimulated leptin secretion from OVX rats compared with SHAM rats was found (P < 0.005) whereas 17 beta-estradiol treatment of ovariectomized rats maintained a normal leptin secretion. However, the dexamethasone stimulation was equally increased above basal levels in SHAM, OVX and EST rats (3.7 +/- 1.2, 2.9 +/- 0.8, 4.2 +/- 1.4, NS, ANOVA) respectively.

Adipose Tissue↗
PubMed1999

Enantioselective high-performance liquid chromatographic method for the determination of methadone and its main metabolite in urine using an AGP and a C8 column coupled serially.

A simple and sensitive method for the enantioselective high-performance liquid chromatographic determination of methadone and its main metabolite, EDDP, in human urine is described. (-)-(R)-Methadone, (+)-(S)-methadone, (+)-(R)-EDDP, (-)-(S)-EDDP and imipramine as an internal standard are detected by ultraviolet detection at 200 nm. The enantiomers of methadone and EDDP were extracted from human urine by a simple liquid-liquid extraction procedure. The extracted sample was reconstructed in mobile phase and the enantiomers of methadone and EDDP were quantitatively separated by HPLC on a short analytical LiChrospher RP8 column coupled in series with a chiral AGP column. Determination of all four enantiomers was possible in the range of 0.03 to 2.5 microM. The recoveries of methadone enantiomers and EDDP enantiomers added to human urine were about 90% and 80%, respectively. The method was applicable for determination of methadone enantiomers and the enantiomers of its main metabolite in urine samples from methadone maintenance patients and patients suffering from severe chronic pain.

Chromatography, High Pressure Liquid↗
PubMed1999

The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells.

AIMS/HYPOTHESIS: The circulating concentrations of endothelin-1 (ET-1), a peptide derived from endothelium, are increased in hypertension and diabetes. Endothelin-1 has recently been shown to be an insulinotropic agent. The mechanism of action of endothelin-1 on the endocrine pancreas has not yet been clarified. METHODS: We investigated the action of endothelin-1 on the insulin secretion, the binding of (125)I-ET-1 to beta cells as well as its effects on purified beta and non-beta cells from normal rats. The expression of endothelin receptors in alpha- and beta-cell lines and in normal rat islets was also studied. RESULTS: First, we studied the effects of endothelin-1 on insulin secretion from beta-cell lines (INS-1, betaTC3 and MIN6). At all endothelin-1 concentrations applied (1 pmol/l to 1 micromol/l) no change in insulin secretion was found. Ligand-binding experiments on betaTC3 cells showed no specific binding of (125)I-ET-1. A prominent expression of ET(A)-receptor mRNA in an alpha-cell line (alphaTC1.9) and in normal rat islets was found whereas no expression was found in INS-1 cells. No influence of endothelin-1(1 micromol/l) on insulin secretion stimulated by glucose was detected from purified beta cells. Endothelin-1-(100 nmol/l) increased, however, both insulin and glucagon secretion from a mixture of purified beta and non-beta cells indicating that alpha cells seem to have a key role for the action of ET-1 on insulin secretion. CONCLUSION/INTERPRETATION: The insulinotropic impact of endothelin-1 is not caused by a direct action on the beta cells but seems to be mediated by a paracrine action, probably secondary to enhanced release of glucagon from the endothelin receptor positive alpha cells. [Diabetologia (1999) 42: 1302-1307]

Animals↗
PubMed1999

Regulation of leptin by thyroid hormone in humans: studies in vivo and in vitro.

The influence of thyroid hormones on human adipose tissue leptin production and leptin gene expression was investigated in vitro and in vivo. Twelve women received 60 microg triiodothyronine (T3) per day for 7 days, which increased total T3 by 195% (1.78 +/- 0.07 to 5.25 +/- 0.39 mU/L, P < .001), significantly decreased thyrotropin ([TSH] 1.57 +/- 0.40 to 0.03 +/- 0.01 mU/L, P < .01), and increased energy expenditure (1,602 +/- 32 to 1,754 +/- 34 kcal/24 h, P < .05). However, serum leptin did not change (9.36 +/- 1.6 v 8.90 +/- 1.3 microg/L, nonsignificant). Human subcutaneous adipose tissue biopsies from eight healthy women were incubated in vitro as small fragments with T3 in concentrations from 1 to 50 nmol/L. Leptin production was inhibited dose-dependently. After 24 hours of incubation, a T3 concentration of 50 nmol/L reduced basal leptin production by 42% (P < .05) and the stimulated leptin production (dexamethasone 10 nmol/L) by 52% (P < .05). Leptin mRNA expression was measured by a semiquantitative multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) method. Fifty nanomolars T3 decreased basal leptin mRNA expression by 47% compared with controls (P < .001), and the stimulated leptin mRNA expression was reduced to a similar degree (53%). In conclusion, in human adipose tissue, T3 (>20 nmol/L) inhibited leptin production and leptin gene expression in vitro, whereas an elevation of T3 corresponding to a moderate thyrotoxic state (T3 5.25 +/- 0.39 nmol/L) was without any impact on serum leptin levels in vivo.

Adipose Tissue↗
PubMed1999

Regulation of uncoupling protein-2 and -3 by growth hormone in skeletal muscle and adipose tissue in growth hormone-deficient adults.

The newly described uncoupling proteins, UCP2 and UCP3, may play a role in regulating energy expenditure (EE) in humans. GH deficiency (GHD) is associated with decreased lean body mass, increased adiposity, and reduced EE, which are reversed by GH treatment. In the present study we investigated whether GH treatment for 4 months influenced the expression of UCPs in skeletal muscle and adipose tissue in 22 GHD patients who were investigated before and after GH (n = 11) or placebo (n = 11) treatment. GH treatment increased the amount of lean body mass by 4.5% (P < 0.05) and decreased body fat mass by 12% (P < 0.05), whereas no changes in these parameters were observed after placebo treatment. The level of UCP3 messenger ribonucleic acid (mRNA) increased 3-fold (P < 0.005) in skeletal muscle and almost 2-fold (P < 0.05) in adipose tissue after GH treatment, with no changes observed after placebo treatment. Skeletal muscle UCP2 mRNA was slightly (25%), but significantly (P < 0.05), decreased, whereas the level of UCP2 mRNA in adipose tissue was unaffected after GH treatment. The T4 level was positively correlated with skeletal muscle UCP2 and UCP3 expression (r = 0.518; P < 0.05 and r = 0.463; P < 0.05, respectively). Furthermore, plasma free fatty acids were positively correlated with the expression of UCP2 (r = 0.573; P < 0.01) and UCP3 (r = 0.518; P < 0.05) in skeletal muscle. The marked increase in UCP3 expression after GH treatment indicates that the UCPs might play a role in the effects of GH on EE in GHD patients. Finally, the strong association between thyroid hormone and skeletal muscle UCP and the correlation between plasma free fatty acids and UCP expression in skeletal muscle indicate that these hormones/metabolites might influence UCP expression in humans as previously demonstrated in rodents.

Adipose Tissue↗