Biomedical subjects

S B Pedersen

Publications and source records attributed to S B Pedersen.

At least 55 records · Page 3Linked to original sources

PubMed1997

Evidence of an increased number of type IIb muscle fibers in insulin-resistant first-degree relatives of patients with NIDDM.

Insulin resistance is a common feature in first-degree relatives of NIDDM patients. To explore the mechanism(s) behind this condition in more detail, a percutaneous muscle biopsy (vastus lateralis) was performed in 25 first-degree relatives of NIDDM patients and 21 control subjects to examine muscle fiber composition and capillary density. Insulin-stimulated glucose disposal (Rd) was determined employing a hyperinsulinemic-(insulin infusion rate 0.6 mU x kg[-1] x min[-1]) euglycemic clamp. Rd (5.76 +/- 0.35 vs. 8.06 +/- 0.36 mg x kg lean body weight [LBW]-1 x min[-], P < 0.001) and estimated VO2max (49.3 +/- 2.8 vs. 57.2 +/- 3.5 mg x kg LBW[-1] x min[-1], 0.05 < P < 0.10) were decreased in the relatives. The number of type IIb fibers (29.5 +/- 2.5 vs. 21.0 +/- 2.8%, P < 0.05) was increased in the relatives, whereas no significant differences were found in other fiber types or capillary density between the groups. Correlations were observed between number of type I fibers (positive), number of type IIb fibers (negative), and capillary density (positive) versus Rd as well as estimated VO2max (P < 0.05). In a multiple linear regression analysis with Rd as a dependent variable, estimated VO2max, family history of NIDDM, and number of type IIb fibers (P < 0.001, r2 = 0.64) significantly determined the level of Rd, whereas capillary density did not. In conclusion, insulin-resistant first-degree relatives of NIDDM patients are characterized by an increased number of type IIb muscle fibers. Whether this finding reflects a reduced physical activity level and fitness in the relatives or is of primary genetic origin remains to be determined.

Adult↗

PubMed1996

[Significance of fat distribution for metabolic risk factors in healthy males of normal weight].

A homogeneous group of non-obese men (n = 58), all 44 years old, were investigated in order to determine whether body fatness and especially abdominal fatness influence the metabolic risk profile in normal-weighted men. In addition, it was investigated which anthropometric measurements that were most closely associated with the risk profile. It was found that enhancement of total fatness, but particularly even a minor accumulation of the adipose tissue in the abdominal region in these otherwise non-obese men, was associated with a considerably adverse metabolic risk profile. Those risk factors that seemed to be most "sensitive" for abdominal fatness were HDL-cholesterol, the atherogenic index, triglyceride and fasting plasma insulin. The sagittal diameter (SD) seemed to be slightly better correlated to the risk profile than other anthropometric indices of abdominal fatness (e.g. WHR).

Abdomen↗

PubMed1996

Identification of oestrogen receptors and oestrogen receptor mRNA in human adipose tissue.

The distribution of adipose tissue has a major impact on the morbidity and mortality associated with obesity. Furthermore, the distribution of adipose tissue seems to be regulated by sex hormones. Controversy exists over whether the effects of sex hormones (oestrogen and testosterone) on human adipose tissue are an indirect or a direct effect as contradictory results have been obtained when investigating the existence of these receptors in human adipose tissue. In the present study the authors reinvestigated the possible existence of oestrogen receptors (ERs) in human adipose tissue. Human adipocytes from both genders were found to contain specific oestrogen binding sites determined by ligand-binding techniques. The binding protein had a molecular weight of 65 kD (which is similar to that of the ER found elsewhere) and it was found that adipocytes contained mRNA encoding the ER. Moreover, human preadipocytes had no oestrogen-binding capacity and did not possess mRNA encoding the ER. Finally, the authors detected regional differences in receptor density. Women had an equal oestrogen-binding capacity in adipose tissue from the subcutaneous abdominal and the visceral depot, whereas men had twice as high oestrogen-binding capacity in subcutaneous adipose tissue compared with adipose tissue in the visceral fat depot. These findings indicate that mature human adipocytes possess ERs and thus, might be an oestrogen-responsive tissue and that oestrogen may be acting directly in mature adipocytes via its specific receptor. Human preadipocytes, however, seemed not to be an oestrogen-responsive tissue. Finally, preliminary data suggest that there might be differences in ER densities in different fat depots.

Abdomen↗

PubMed1996

Identification of steroid receptors in human adipose tissue.

Steroids have the ability to alter adipose tissue distribution. Controversy exists as to whether these effects of sex hormones (oestrogen, progesterone and testosterone) on human adipose tissue are indirect or direct, as only very few studies have focused on steroid receptor status in human adipose tissue. In the present study, we reinvestigated steroid receptor status in human mature adipose tissue and human preadipocytes. Oestrogen, glucocorticoid and androgen receptors were found in human mature adipocytes from both women and men. The receptors were detected by ligand binding. Furthermore, the existence of the receptors was confirmed by demonstrating that adipocytes contained mRNA encoding the receptors. cDNA was generated using reverse transcriptase (RT) followed by polymerase chain reaction (PCR) amplification using specific primers (RT-PCR) for the specific steroid receptors. Adipocytes did not contain mRNA encoding the progesterone receptor (PR), and no progesterone binding was detectable in human adipocytes. Human preadipocytes contained glucocorticoid receptor (GR) mRNA and androgen receptor (AR) mRNA, whereas we were unable to detect oestrogen receptor (ER) mRNA and progesterone mRNA in human preadipocytes. In conclusion, oestrogen glucocorticoid and androgen receptors are present in mature adipocytes from subjects of both sexes, whereas adipocytes do not contain progesterone receptors. In preadipocytes, only glucocorticoid receptors and androgen receptors are present, whereas oestrogen receptors and progesterone receptors are not present.

Adipose Tissue↗

PubMed1996

Nitric oxide-donating properties of mesoionic 3-aryl substituted oxatriazole-5-imine derivatives.

1. The nitric oxide (NO)-releasing properties of two new mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (GEA 3162 and GEA 3175) were characterized and compared with the known NO-donors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2. GEA 3162, GEA 3175, SIN-1 and SNAP inhibited adenosine 5'-diphosphate-induced platelet aggregation (IC50 values 0.18, 0.39, 3.73 and 2.12 microM, respectively). All four compounds induced a dose-dependent and more than 4 fold increase in cyclic GMP in platelets. The increase in cyclic GMP concentration was potentiated more than 1.5 fold by a phosphodiesterase inhibitor, zaprinast (10 microM) and inhibited 38-97% by oxyhaemoglobin (10-45 microM). 3. All of the four compounds studied converted oxyhaemoglobin to methaemoglobin and formed a paramagnetic NO-haemoglobin complex. All but GEA 3175 formed nitrite and nitrate in phosphate buffer. During a 40 min incubation, GEA 3162, SIN-1 and SNAP (100 microM) produced 50-70 microM NO2- + NO3- as determined by high performance liquid chromatography. The release of NO and NO2 by GEA 3175 was increased 140 fold in the presence of human plasma (0.14 and 19.7 ppb in the absence and presence of 1% human plasma, respectively) as analyzed by ozone chemiluminescence. 4. The results suggest that the mesoionic 3-aryl substituted oxatriazole-5-imine derivatives GEA 3162 and GEA 3175 as well as SIN-1 and SNAP release nitric oxide.

Blood Platelets↗

PubMed1996

Long-term (6 months) effect of a new fermented milk product on the level of plasma lipoproteins--a placebo-controlled and double blind study.

OBJECTIVE: We have recently demonstrated a short-term hypocholesterolemic effect (reduction of 8-10%) of a new fermented milk product taken for 6 weeks (Agerbaek et al, 1995; Richelsen et al, 1993). The present study was undertaken to investigate the more long-term (6 months) effect of this fermented product on the level of lipoproteins. DESIGN: The study was randomized, double-blind, and placebo-controlled, and performed for a period of six months. SUBJECTS: Eighty-seven non-obese and normocholesterolemic females and males, aged 50-70 y old, were included in the study. INTERVENTION: 200 ml of either the fermented milk product or placebo (chemically fermented) were given daily. The test product was fermented with a bacteria culture containing Enterococcus faecium and two strains of Streptococcus termophilus. RESULTS: After one month the total- and LDL-cholesterol were significantly reduced in the fermented milk group as compared to placebo, LDL was reduced by 0.21 mmol/l vs 0.0 mmol/1 (P < 0.02). The maximal reduction of LDL-cholesterol was reached after 3 months in the test group with a reduction of 0.32 mmol/1 of initial values (P < 0.001). In the placebo group a gradual fall of total- and LDL-cholesterol was observed from 1-6 months of the study. Thus, after six months the reduction of LDL-cholesterol was similar in the two groups (P = 0.95) even though the reduction was significant in both groups in relation to initial values (P < 0.05). No changes in HDL-cholesterol or triglyceride were observed during the study. There were no differences in the response between women and men. CONCLUSION: The fermented milk product resulted in a rapid reduction of LDL-cholesterol observed after one month but during long-term intake (6 months) the reduction of LDL-cholesterol was similar to the placebo product, indicating that low-fat milk or fermented milk products may have some hypocholesterolemic effects but the present tested product does not seem to be superior in that respect to the placebo milk product used in the present study.

Aged↗

PubMed1995

Inhibition of renal ornithine decarboxylase activity fails to reduce kidney size and urinary albumin excretion in diabetic rats with manifest kidney hypertrophy.

Formation of polyamines has previously been shown to play an important role for initial kidney growth in experimental diabetes, as treatment of diabetic rats with a selective ornithine decarboxylase (ODC) inhibitor, initiated immediately after diabetes induction, abolishes the initial kidney growth. In order to investigate the role of polyamine formation for the maintenance of diabetic kidney hypertrophy, ODC inhibition was initiated after manifest kidney hypertrophy had occurred. The kidney weight in diabetic rats was significantly larger than in control rats after a diabetes duration of 7, 14, 50 and 71 days and the total glomerular volume was increased in kidneys from diabetic rats after a diabetes duration of 71 days. Renal activity of ODC was increased in diabetic rats throughout the study period of 71 days. Treatment of diabetic rats with the selective ODC inhibitor di-fluoro-methyl-ornithine (DFMO) was maintained for two periods (days 7-14 and days 50-71). DFMO treatment had no effect on 24-h food consumption, blood glucose concentration or body weight. However, despite almost total inhibition of the kidney ODC activity, there was no effect on kidney growth or total glomerular volume in the DFMO treated diabetic rats compared to placebo treated diabetic rats. Finally, the urinary albumin excretion was markedly increased in diabetic rats with no effects of ODC-inhibition. In conclusion, inhibition of ODC initiated in diabetic rats with manifest kidney enlargement had no effect on renal size, glomerular volume or urinary albumin excretion. These findings together with our previous findings indicate that the role of polyamines in diabetic kidney enlargement is restricted to the first week after diabetes induction.

Albuminuria↗

PubMed1995

Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study.

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Relationship between sex hormones, body composition and metabolic risk parameters in premenopausal women.

The metabolic complications associated with obesity are dependent upon the degree of obesity and the distribution of adipose tissue. In order to evaluate the associations between sex hormone status, metabolic risk parameters, obesity and distribution of adipose tissue, 25 premenopausal women with a wide range of body mass index (19.3-48.1 kg/m2 were studied. Body composition was determined by dual-energy x-ray absorptiometry scan and anthropometric measurements; in addition, lipid and sex hormone status were determined and an oral glucose tolerance test was performed. We found that sex hormone-binding globulin was correlated negatively with total fat mass (r = -0.77, p < 0.001) and especially with abdominal localization of adipose tissue (r = -0.85, p < 0.001). Free testosterone was correlated positively with total fat mass (r = 0.40, p < 0.05) and with abdominal fat accumulation (r = 0.64, p < 0.001). Free estrogen was correlated negatively with total amount of adipose tissue (r = -0.40, p < 0.05) but not with the distribution of adipose tissue. Finally, total fatness, abdominal localization of adipose tissue and free testosterone were all associated with elevated metabolic risk factors. However, multiple regression analysis revealed that only abdominal localization of adipose tissue was independently associated with a higher risk profile, whereas the effects of sex hormones or total fatness disappeared when abdominal localization of adipose tissue was included in the analysis. In conclusion, these findings in premenopausal women indicate that the connection between sex hormones and metabolic risk factors might be indirect, probably operating through alterations in the amount of adipose tissue in the abdominal region.

Adipose Tissue↗

PubMed1995

Associations between different anthropometric measurements of fatness and metabolic risk parameters in non-obese, healthy, middle-aged men.

OBJECTIVE: To investigate whether body fatness influences the metabolic risk profile in a group of healthy, normal-weighted men and to determine which anthropometric measurements that are most closely associated with the risk profile in this group of men. DESIGN: A cross-sectional study where total fatness and abdominal fatness were determined by older (BMI, WHR, impedance) and more recent anthropometric indices (sagittal diameter (SD) and conicity index (Valdez et al., Int. J. Obes. 1993; 17: 955)). The metabolic risk profile was determined by lipoproteins, insulin, glucose and blood pressure. SUBJECTS: The study comprised a homogeneous group of 58 men who were all healthy and normal-weighted (BMI = 24.2 +/- 1.8) and were all 44 years old. RESULTS: In relation to total fatness, BMI was more closely correlated to the various risk parameters than the fat mass determined by bioelectrical impedance independent of using several different equations in estimating the fat mass. From simple comparison of correlation coefficients, SD and SDH (SD/height) seemed to be the best indices of abdominal fatness in predicting an enhanced metabolic risk profile. The conicity index was considerably inferior in comparison to the other indices of abdominal fatness. In multiple regression analysis abdominal fatness as determined by SD or SDH explained most of the variation in the metabolic risk profile and no significant influence of total fatness (BMI) was found when taking the influence of abdominal fatness into account. The most pronounced effect of abdominal fatness in these non-obese men was a reduction of HDL-cholesterol, an elevation of the triglycerid level and an elevation of the insulin level. CONCLUSION: Thus, even a minor accumulation of adipose tissue in the abdominal region in these otherwise non-obese men was associated with a considerably adverse metabolic risk profile. SD or SDH seemed to be slightly more correlated to the risk profile than other anthropometric indices of abdominal adipose tissue mass (e.g. WHR). The new conicity index was inappropriate for predicting the risk profile associated with abdominal fatness in these non-obese men.

Abdomen↗

PubMed1994

Augmented effect of short-term pulsatile versus continuous insulin delivery on lipid metabolism but similar effect on whole-body glucose metabolism in obese subjects.

The present study was designed to examine the effect of pulsatile versus continuous insulin delivery on glucose and lipid metabolism in insulin-resistant subjects. Six obese women (body mass index, 40.0 +/- 2.8 kg/m2) underwent a euglycemic glucose clamp (plasma glucose, 90 mg/dL) twice. In random order, insulin was infused intravenously for 375 minutes either at a constant rate (0.4 mU/kg/min) or in a pulsatile manner (2.4 mU/kg/min for 2 minutes followed by an off interval of 10 minutes). Endogenous insulin release was suppressed by infusion of somatostatin (250 micrograms/h). Mean circulating insulin concentrations were similar during the two protocols (pulsatile v continuous infusion, 60 +/- 10 v 56 +/- 9 mU/L), but pulsatile infusion was accompanied by oscillations with an amplitude of 120 mU/L. After 6 hours of pulsatile versus continuous insulin, isotopically determined total glucose disposal (3-3H-glucose) and hepatic glucose production (HGP) were comparable (pulsatile v continuous, 2.80 +/- 0.56 v 2.82 +/- 0.51 and 0.37 +/- 0.14 v 0.32 +/- 0.17 mg/kg/min). However, the rate of glucose oxidation (indirect calorimetry) was augmented (P < .05), whereas lipid oxidation tended to be diminished (.10 > P > .05) following pulsatile infusion. In addition, blood glycerol was more suppressed with pulsatile (31 +/- 9 nmol/L) than with continuous infusion (36 +/- 10 nmol/L, P < .05), whereas blood lactate, alanine, and 3-hydroxybutyrate were similar in the two infusion protocols.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1994

Fuel metabolism, energy expenditure, and thyroid function in growth hormone-treated obese women: a double-blind placebo-controlled study.

Growth hormone (GH) promotes protein anabolism and lipolysis. Its effects on glucose metabolism include suppression of glucose oxidation and may be associated with insulin resistance. In addition, GH stimulates energy expenditure (EE) and peripheral thyroid hormone metabolism. GH secretion is reduced in obese patients, but whether this is of pathophysiological significance is incompletely understood. In a double-blind placebo-controlled crossover design, we studied the effects of GH administration (0.03 mg.kg ideal body weight [IBW]-1.d-1) on fuel metabolism, EE, and thyroid function in 10 obese women (age, 30.4 +/- 2.4 years; body mass index [BMI], 37.0 +/- 2.8 kg/m2, mean +/- SE) with a normal prestudy oral glucose tolerance test (OGTT). Each treatment period (GH or placebo) lasted 5 weeks, separated by a 5-week washout period. At the end of each treatment period, subjects were studied in the basal state (8:00 AM) and during a euglycemic glucose clamp including indirect calorimetry and isotopic measurement of glucose turnover. Lean body mass (LBM) was assessed at the end of each period by dual-energy x-ray absorptiometry. In the basal state, GH induced a significant increase in circulating levels of free fatty acids (FFA), glucose, insulin, and C-peptide. This was associated with a significant increase in resting EE (kcal/24 h, 1,934 +/- 92 placebo v 2,323 +/- 134 GH, P < .001), a decrease in the respiratory exchange ratio (RER), and increased rates of lipid oxidation (mg.kg LBM-1.min-1, 1.55 +/- 0.09 placebo v 2.20 +/- 0.13 GH, P < .01). GH increased the rate of total basal glucose turnover, whereas oxidative glucose disposal was significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Biopharmaceutical aspects of tolfenamic acid.

The pharmacokinetics of tolfenamic acid is well described by a two-compartment model with relatively short half-lives (T/2 beta 1-2 hours) and tolfenamic acid is highly protein-bound with small volumes of distribution. It is cleared relatively fast (150-200 ml/min), mainly by hepatic metabolism and the metabolites are renally cleared as glucuronic acid conjugates. The peroral absorption is good and the peroral bioavailability is about 75%, as first pass metabolism accounts for about 20%. Tolfenamic acid shows linear pharmacokinetics and during multiple dosage regimen, i.e. thrice daily, no accumulation beyond the second dose is observed. The bioavailability in dependence of age and disease has been studied and only in the case of severe liver or kidney impairment, a change in dosage regimen seems warranted. The development of different formulations will be outlined, mainly on rectal delivery, on sustained release and rapid release oral formulations, on topical ointment, and on parenteral delivery. The problems with tolfenamic acid in pharmaceutical formulation caused mainly by poor solubility will be discussed. Formulations ready for the market now or very soon are Clotam capsules (tablets). Clotam retard tablets, Clotam suppositories, and Clotam oral suspension, whereas rapid tablets, topical ointments, and parenteral formulations need further development to be ready for marketing in the years to come.

Absorption↗

PubMed1994

Growth hormone treatment of obese women for 5 wk: effect on body composition and adipose tissue LPL activity.

Because it has been found that growth hormone (GH) treatment of GH-deficient adults is able to reduce the total fat mass, the present study was undertaken to investigate the effect of GH treatment in obese subjects. The investigation was a double-blind placebo-controlled crossover study in which nine obese females were treated with GH (0.03 mg.kg ideal body wt-1.day-1) and placebo for 5 wk. Body composition was determined by dual-energy X-ray absorptiometry, and the quantity of intra-abdominal adipose tissue was determined by CT scan. Lipoprotein lipase (LPL) activity was determined in fat biopsies taken from the subcutaneous abdominal and gluteal region. GH treatment significantly reduced the total fat mass from 40.5 to 38.4 kg (i.e., 5% reduction of the total fat mass; P < 0.01), whereas the fat-free mass increased from 50.5 to 53.5 kg (P < 0.01). In addition, GH treatment significantly reduced the intra-abdominal adipose tissue determined by CT scan (reduction by 7 +/- 0.3%; P < 0.02). CT scan performed at the level of the femur showed a 7% reduction in adipose tissue and a 5% increase in muscle volume in the GH group (P < 0.05). Thus no clear regional differences in the GH-mediated reduction of the adipose tissue mass were observed. GH reduced the LPL activity by approximately 50% (P < 0.01) in the adipose tissue. Finally, GH treatment significantly increased the level of plasma free fatty acids (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1994

Characterization of regional and gender differences in glucocorticoid receptors and lipoprotein lipase activity in human adipose tissue.

Glucocorticoid receptor (GR) status was studied in adipose tissue from omental and sc abdominal adipose tissue. As the effects of glucocorticoids may be due to alteration of triglyceride uptake in adipose tissue, the activity of the enzyme lipoprotein lipase (LPL) was also investigated. Fat biopsies were obtained from 8 women and 11 men matched for age and body mass index. Omental adipose tissue contained 4 times the number of GR as sc abdominal adipose tissue (42.0 +/- 4.1 vs. 10.5 +/- 2.3 fmol/mg protein, respectively; P < 0.001) with similar Kd values. No gender difference in GR number was observed in adipose tissue from the two regions. LPL activity in omental adipose tissue was about 820 nmol FFA/h.g wet wt in both sexes, whereas LPL activity in sc adipose tissue was about 2- to 4-fold lower. Moreover, LPL activity in sc adipose showed marked gender differences, with 2-fold higher activity in women than in men (474 +/- 84 vs. 238 +/- 35 nmol FFA/h.g wet weight; P < 0.03). Finally, there was no correlation between GR number and LPL activity when each fat depot was investigated separately. However, a positive correlation between LPL activity and glucocorticoid binding was found when the data from both regions were pooled (r = 0.55; P < 0.01). In conclusion, human adipose tissue dexamethasone binding was higher in omental than in sc adipose tissue, without any gender difference. LPL activity was also higher in omental than in sc adipose tissue in both groups, without any gender difference. On the other hand, sc LPL activity was higher in females than in men. A correlation (positive) between GR number and LPL activity was only found when the data from both regions were pooled.

Adipose Tissue↗

PubMed1993

Abdominal obesity is associated with insulin resistance and reduced glycogen synthetase activity in skeletal muscle.

Insulin resistance is commonly associated with obesity. The present study was performed to investigate the relative importance of total fat mass versus localization of adipose tissue in insulin-stimulated glucose disposal (Rd) and skeletal muscle glycogen synthase (GS) activity in obese individuals. Twenty obese women with an average body mass index (BMI) of 37.8 +/- 1.3 kg/m2 and a waist to hip ratio (WHR) ranging from 0.78 to 1.02 were examined during basal conditions and following hyperinsulinemia (hyperinsulinemic euglycemic clamp). To accurately determine body composition, the following three methods were used: anthropometric measurements, dual-energy x-ray absorptiometry scanning (DEXA-scan), and bioelectric impedance measurements. In addition, indirect calorimetry and muscle biopsy were performed. Insulin-stimulated glucose Rd was negatively correlated with WHR (R = -.52, P < .025) whereas there were no correlations with BMI or percent fat (R = .16, NS and R = .16, NS, respectively). Furthermore, a negative correlation between WHR and insulin stimulation of GS activity in skeletal muscle was found (R = -.62, P < .005). In contrast, BMI and percent fat were not correlated with the insulin effect on GS activity in skeletal muscle (R = .34, NS and R = -.35, NS, respectively). The concentration of nonesterified fatty acids (NEFA) during hyperinsulinemia was strongly correlated with WHR and abdominal localization of adipose tissue (determined by DEXA-scan; R = .60, P < .005 and R = .60, P < .007, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1993

Lipoprotein lipase activity in muscle tissue influenced by fatness, fat distribution and insulin in obese females.

Obesity is associated with dyslipidaemia and increased morbidity and mortality from premature atherosclerosis and diabetes mellitus. Particularly, hypertriglyceridaemia is a characteristic finding in patients with obesity. In addition, the elevated levels of triglycerides may be an important risk factor for development of the obesity-related complications. Lipoprotein lipase activity in skeletal muscle tissue (mLPL) has previously been found to be an important factor regulating the concentration of serum triglycerides. To describe the relationship between mLPL, triglycerides and fatness/fat distribution in more detail we have investigated these parameters under basal conditions and during insulin stimulation in 20 obese females. During hyperinsulinaemia (204 microU ml-1) for 4 h the mLPL activity decreased from 528 +/- 52 nmol FFA g-1 to 412 +/- 44 (P < 0.001). Basal mLPL was negatively correlated with serum triglycerides (r = -0.48, P < 0.05) and positively correlated with HDL-cholesterol (r = 0.58, P < 0.01). Employing multiple variance analysis it was found that both BMI and WHR were negatively correlated to mLPL, however, the impaired lipid profile (high triglyceride, low HDL-cholesterol, high FFA) could only be related to BMI and not to WHR in these obese females. However, reduced insulin-action (insulin resistance) was closely related to abdominal fatness determined by WHR both in relation to the insulin-effect on mLPL as well as for the insulin-effect on whole-body glucose metabolism (clamp-study).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1993

Inhibition of renal ornithine decarboxylase activity prevents kidney hypertrophy in experimental diabetes.

The selective ornithine decarboxylase (ODC) inhibitor difluoromethyl ornithine (DFMO) was used to investigate the role of polyamines in initial diabetic renal enlargement. ODC activity in kidneys from diabetic animals was increased (fivefold) 24 h after diabetes induction (P < 0.05), and throughout the study (7 days) the activity remained 2- to 3-fold elevated (P < 0.05). Insulin treatment normalized renal ODC activity, whereas DFMO treatment totally inhibited the kidney ODC activity. The kidney weight in diabetic rats was 21% higher than that of control rats (1,074 +/- 35 mg and 889 +/- 16 mg, P < 0.001). Insulin treatment normalized kidney weight (847 +/- 13 mg). Despite unaltered diabetic metabolic aberrations the kidney weight in DFMO-treated diabetic rats was normalized (911 +/- 7 mg). In conclusion, the ODC activity in diabetic kidneys undergoing hypertrophy was increased. Insulin treatment normalized both kidney weight and kidney ODC activity. Finally, selective inhibition of ODC activity by DFMO resulted in kidneys of normal size, despite unaltered diabetic metabolic aberrations. These findings support the hypothesis that polyamines play an important role in initial diabetic renal enlargement.

Animals↗