A Kocijancic

University Medical Centre Maribor, Maribor, Mestna Obcina Maribor, Slovenia

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Publications (47)110.36 Total impact

  • Andrej Zavratnik, Janez Prezelj, Andreja Kocijancic, Janja Marc
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    ABSTRACT: Studies have shown that selective modulator of estrogen receptor raloxifene, exerts hypolipemic properties at least partially through estrogen receptor alpha activation. To test the hypothesis that polymorphisms of estrogen receptor alpha are associated with the influence of 6 months raloxifene treatment on serum lipids, two intronic (PvuII and XbaI), and one exonic polymorphism (P325P) were analyzed in 49 postmenopausal women, mean age 62.5+/-5.7 years. In all subjects, the total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were determined before and after 6 months of raloxifene treatment. We were unable to find any relationship between estrogen receptor alpha genotype and serum lipids at baseline. At the end of 6 months treatment with raloxifene, the mean decrease of total cholesterol and LDL cholesterol, independently of genotypes, was highly significant, but no influence on HDL and triglycerides concentrations was found. Neither the PvuII nor XbaI ESR1 gene polymorphisms were associated with the magnitude of lipid changes after 6 months treatment, whereas the subjects with non-CC genotype of P325P mutation had significantly lower total cholesterol and LDL cholesterol concentrations, and higher decline of total cholesterol (p<0.05). CONCLUSION: Our data suggest that exonic, but not intronic polymorphisms of estrogen receptor alpha gene might intensify the cholesterol lowering effect of raloxifene.
    The Journal of Steroid Biochemistry and Molecular Biology 04/2007; 104(1-2):22-6. · 3.98 Impact Factor
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    ABSTRACT: Incipient cardiovascular autonomic imbalance is not readily diagnosed by conventional methods. Spectral analysis of heart rate variability (HRV) by wavelet transform (WT) was used to measure cardiovascular autonomic function in patients with Type 2 diabetes. Thirty-two diabetic patients without (D), 26 with cardiovascular autonomic neuropathy (DAN) and 72 control subjects (C) participated. A 30-min HRV time series was analysed by wavelet transformation and four characteristic frequency intervals were defined: I (0.0095-0.021 Hz), II (0.021-0.052 Hz), III (0.052-0.145 Hz) and IV (0.145-0.6 Hz). When compared with C, in both D and DAN the normalized power and amplitude of interval II were increased and of interval IV decreased, resulting in a significantly higher II/IV ratio. Furthermore, in DAN the normalized power and amplitude of interval I were increased and of interval III decreased when compared with the D and C groups. The diabetic patients were divided in two equal subgroups according to HbA(1c) < 8.0% and >or= 8.0%. In the subgroup with HbA(1c) >or= 8.0%, normalized power in interval II was significantly higher and in interval IV significantly lower than in the subgroup with HbA(1c) < 8.0%. In D, but not in DAN patients prescribed ACE inhibitors, the absolute amplitude and power of oscillations were significantly higher than in patients not taking ACE inhibitor therapy. Patients with diabetes have increased sympathetic and decreased parasympathetic cardiac activity regardless of the presence of autonomic neuropathy. Glycaemic control and treatment with ACE inhibitors may favourably influence HRV in diabetic patients without autonomic neuropathy.
    Diabetic Medicine 02/2007; 24(1):18-26. · 3.24 Impact Factor
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    ABSTRACT: The receptor activator of nuclear factor-kappaB ligand (RANKL) is recognized as one of the important regulators of osteoclastogenesis. The expression of the tumour necrosis factor superfamily, member 11 (TNFSF11) gene, which encodes for RANKL protein, is increased relative to the expression of osteoprotegrin in cases of senile osteoporosis with hip bone fracture. Our aim was to find polymorphisms in the TNFSF11 gene promoter and to investigate their possible association with bone mineral density (BMD). The TNFSF11 gene promoter region was screened for the presence of new sequence variations by direct sequencing. DNA sequencing revealed the presence of four sequence variations: -290C>T, -643C>T, -693G>C and -1594G>A. Association of the discovered polymorphisms with BMD was investigated in 115 Slovenian postmenopausal women, using restriction fragment length polymorphism analysis. After a year, bone loss in the association with the identified sequence variations was evaluated in 43 postmenopausal women. Three of the discovered sequence variations (-290C>T, -643C>T, -693G>C) proved to be polymorphic, whereas variation -1594G>A was only found in one patient. The frequencies of genotypes were as follows: CC (27.8%), CT (43.5%), TT (28.7%) for -290C>T polymorphism; CC (23.5%), CT (47.8%), TT (28.7%) for -643C>T polymorphism; and GG (22.6%), GC (51.3%), CC (26.1%) for -693G>C polymorphism. A statistically significant association of genotype with BMD at the femoral neck was observed only in the -290C>T polymorphism. Genotype CC was associated with lower BMD than the TT genotype (P = 0.022). In polymorphism -693G>C, a significant difference in bone loss rate was observed in total hip (P = 0.011) and femoral neck BMD (P = 0.037). Four sequence variations were identified in the studied region of TNFSF11 gene promoter. Our results of preliminary clinical evaluation suggest that the -290C>T polymorphism in the TNFSF11 gene promoter could contribute to the genetic regulation of BMD.
    Maturitas 10/2006; 55(3):219-26. · 2.84 Impact Factor
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    ABSTRACT: Impaired blood supply is a significant risk factor for diabetic foot ulceration and gangrene. A possible relationship between peripheral macroangiopathy and the spectral components of microvascular skin blood flow in the lower extremities was tested in diabetic patients (DP) and non-diabetic subjects (C). Basal skin blood flow (BSBF) was recorded for 30min at the right and left medial malleolus (predominantly nutritive capillary circulation) by laser Doppler flowmetry in 64 DP and 31 C. Its oscillatory components were analyzed using wavelet transform. Peripheral arterial obliterative disease (PAOD) was defined according to ankle/brachial index (ABI): PAOD+ (ABI<0.9: 21 DP, 12 C), PAOD- (ABI 0.91-1.3: 43 DP, 19 C). No statistically significant differences in BSBF and its oscillatory components were observed between PAOD+ and PAOD-, neither in DP nor in C. In DP, the spectral component of microvascular flow associated with endothelial activity was in significant positive correlation with systolic pressures on brachial and dorsal pedal artery (p=0.001 and 0.010, respectively). These results indicate that mean BSBF and its oscillatory components do not change with diabetic PAOD; however there is a strong correlation between systolic pressure and the oscillatory components of BSBF related to endothelial activity manifested in the frequency interval 0.0095-0.02Hz.
    Diabetes Research and Clinical Practice 08/2006; 73(2):166-73. · 2.74 Impact Factor
  • M Legan, J Osredkar, S Fisker, A Kocijancic
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    ABSTRACT: GH and IGF system components are important regulators of bone formation and at the same time pathogenetic factors in functional hyperandrogenism (FH) in lean females. We studied the relationships between bone mineral density (BMD) and serum concentrations of GH, GH-related parameters, androgens and estrogen, in 18 non-obese women of reproductive age with functional hyperandrogenism compared to a group of 10 healthy eumenorrheic age- and weight-matched women. In androgenized women, a significant positive correlation was found between BMD and GH-binding protein (GHBP), whereas BMD did not correlate to GH or other related parameters. It is suggested that higher tissue GH receptor responsiveness in non-obese androgenized women may contribute to their higher BMD.
    Journal of endocrinological investigation 03/2006; 29(2):154-8. · 1.65 Impact Factor
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    ABSTRACT: Periprosthetic bone loss after arthroplasty may threaten prosthesis survival. The current study investigated the effect of etidronate therapy on periprosthetic, contralateral hip, and spine bone mineral density (BMD) in a one-year, prospective, randomized, double-blind study on 46 patients after cemented hip arthroplasty. BMD was measured with dual-energy X-ray absorptiometry (DXA). There were no significant differences between mean BMD measurements of the etidronate and placebo groups, with the exception of the mean percent change in the spine at six months and 12 months and in Gruen zone 3 at six months; in all three cases, the etidronate group had significantly greater mean values. These findings suggest that cyclic etidronate therapy has no significant effect in suppressing periprosthetic bone loss following cemented hip arthroplasty.
    International Orthopaedics 01/2006; 29(6):362-7. · 2.32 Impact Factor
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    Maja Jekovec-Vrhovsek, Andreja Kocijancic, Janez Prezelj
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    ABSTRACT: Osteopenia is common in children, adolescents, and young adults with severe cerebral palsy (CP; spastic quadriplegia) living in residential care, and frequently results in atraumatic fractures. On clinical grounds 67 patients (34 males, 33 females) with severe CP (gross motor function classification system [GMFCS] levels IV or V) aged 5 to 25 years (median 20 y) were divided into three groups with increasing likelihood of severe impairment of bone quality: (1) patients without fractures and without anticonvulsant medication (n=13); (2) patients without fractures and with anticonvulsant medication (n=45); (3) patients with fractures and with anticonvulsant medication (n=9). Evaluation included measurements of quantitative ultrasound (QUS) of the calcaneus, multiple serum analyses, and determination of urinary bone-resorption markers. Values of the quantitative ultrasound index (QUI) were significantly different (p=0.001): group 1 (median 56.9; interquartile range 43.8-75.3); group 2 (49.9; 40.0-60.0); group 3 (35.6; 30.5-38.5). when comparing values of laboratory serum and urine in the three groups, we found significant differences in values of serum bone alkaline phosphatase (p=0.001), serum parathyroid hormone (PTH; p=0.002), serum albumin (p=0.020), and urinary deoxypyridinoline/creatinine ratio (p=0.004). In multiple regression analysis, no laboratory variable was found to be an independent predictor of QUI. QUS of the calcaneus may be a useful method to assess bone quality and fracture risk in children and young adults with severe cp living in residential care, independent of information from laboratory data.
    Developmental Medicine & Child Neurology 11/2005; 47(10):696-8. · 2.68 Impact Factor
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    ABSTRACT: Osteoprotegerin (OPG) is a recently discovered member of the tumour necrosis factor receptor superfamily. It plays a crucial role in the control of bone resorption and its gene could therefore be a good candidate gene for osteoporosis. The aim of our work was to find polymorphisms in the OPG gene and to investigate their possible contribution to the genetic susceptibility to osteoporosis by testing for their association with bone mineral density (BMD). The whole OPG gene coding region was screened for the presence of polymorphisms in a group of 60 osteoporotic women by single-strand conformation polymorphism analysis (SSCP) approach. Association of the discovered polymorphisms with bone mineral density was investigated in 136 Slovenian postmenopausal women. We detected eight OPG gene polymorphisms that were confirmed by direct DNA sequencing, deletion 4752_4753delCT and nucleotide substitutions 1181G>C, 1217C>T, 1284G>A, 4501C>T, 6893A>G, 6950A>C and 8738T>A. Nucleotide substitutions 1284G>A and 8738T>A have not been previously described. Polymorphisms 4752_4753delCT, 6893A>G and 6950A>C were in complete linkage and the same was true for 1217C>T and 4501C>T. The association with BMD was found only for polymorphism 1181G>C. Subjects with genotype 1181GG had significantly lower lumbar spine BMD than subjects displaying 1181GC. By our approach we detected eight polymorphisms in the OPG gene. According to our analysis polymorphism 1181G>C is associated with BMD and could therefore be considered as an element of genetic susceptibility to osteoporosis. -----------------------------------------------------------------------------------------------------------------LINK: http://www.sciencedirect.com/science/article/pii/S0378512204002749
    Maturitas 07/2005; 51(3):270-9. · 2.84 Impact Factor
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    ABSTRACT: We investigated the potential effects of chromium supplementation on QTc interval duration in type 2 diabetic patients. Of 60 patients with type 2 diabetes mellitus, 30 were randomly assigned to group A, and 30 to group B. Group A received 1000 microg of chromium picolinate (CrPic) daily for 3 months, followed by placebo in the next 3 months; group B was treated with placebo for the first 3 months and CrPic in the next 3 months. At each visit, QT interval was measured on a standard electrocardiogram by averaging 3 consecutive beats in leads II and V4 and corrected for heart rate with Bazett formula. Although baseline QTc interval was similar in both groups (422 +/- 34 milliseconds in group A vs 425 +/- 24 milliseconds in group B, P = .77), QTc interval at 3 months was shorter in group A (406 +/- 35 milliseconds) than in group B (431 +/- 26 milliseconds, P = .01). In the following 3 months, QTc interval shortened in group B but not in group A, which resulted in a comparable QTc interval duration of both groups at the end of the study (414 +/- 28 milliseconds in group A vs 409 +/- 22 milliseconds in group B, P = .50). Apart from body mass index (31.4 +/- 4.2 kg/m2 in patients with QTc shortening vs 28.7 +/- 4.2 kg/m2 in patients without QTc shortening, P = .03), none of the clinical and laboratory variables predicted QTc interval shortening in our patient cohort. Short-term chromium supplementation shortens QTc interval in patients with type 2 diabetes mellitus.
    American heart journal 05/2005; 149(4):632-6. · 4.65 Impact Factor
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    ABSTRACT: Decreased renal functional reserve might precede incipient diabetic nephropathy in patients with Type 1 diabetes. The aim of this study was to assess the relationship between renal functional reserve and easily assessable estimates of systemic endothelial dysfunction in normoalbuminuric patients with Type 1 diabetes and diabetic retinopathy. Renal functional reserve was calculated as the relative change in glomerular filtration rate after protein ingestion. Glomerular filtration rate was measured using pharmacokinetic compartmental analysis of single-shot plasma sinistrin clearance. We measured the activity of von Willebrand factor and concentrations of C-reactive protein and apolipoprotein B, as easily assessable estimates of systemic endothelial dysfunction. Twenty-two patients were studied. Renal functional reserve was inversely associated with activity of von Willebrand factor (R=-0.431, p=0.045) and, in a multivariate model, with concentration of C-reactive protein (R=0.652, p=0.031). Renal functional reserve is inversely associated with concentration of C-reactive protein in normoalbuminuric patients with Type 1 diabetes and diabetic retinopathy. This finding provides evidence that decreased renal functional reserve might reflect endothelial dysfunction. We speculate that decreased renal functional reserve might possibly show as an early marker of diabetic nephropathy.
    Wiener klinische Wochenschrift 05/2004; 116(7-8):246-51. · 0.81 Impact Factor
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    ABSTRACT: Microvascular blood flow in the human skin is subject to rhythmic variations reflecting the influence of heartbeat, respiration, intrinsic myogenic activity, neurogenic factors and endothelial activity. The aim of our study was to test the hypothesis that basal skin blood flow (BSBF) and its dynamic components differ (1) among diabetic patients without autonomic neuropathy and with it and healthy control subjects, and (2) among the upper and lower extremities. BSBF at four recording sites with predominantly nutritive capillary circulation (right and left caput ulnae, right and left medial malleolus) was measured by laser Doppler flowmetry in 25 diabetic patients without cardiovascular autonomic neuropathy (D), 18 neuropathic diabetic patients (DAN) and 36 healthy controls (C). Wavelet transform was applied to the laser Doppler signal. In absolute terms, mean flow, mean amplitude of the total spectrum and mean amplitudes at all frequency intervals were highest in C, followed by DAN and lowest in D. However, these differences were statistically significant only in the left arm. Within all three groups, mean flow and spectral amplitudes were significantly higher in the arms than in the legs, besides there was a significant difference between the two arms in D. We have confirmed the differences in BSBF among D, DAN and C, and demonstrated differences among the four recording sites which have not been previously described. The latter indicates an uneven progression of autonomic neuropathy and allows for speculation that the left arm is the latest to be affected.
    Journal of Vascular Research 01/2004; 41(6):535-45. · 2.43 Impact Factor
  • Journal of The American College of Cardiology - J AMER COLL CARDIOL. 01/2004; 43(5).
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    ABSTRACT: With the aim to determine whether bone metabolism in young women using low-dose oral contraception is influenced by vitamin D receptor (VDR) genotype, we designed the prospective clinical study of 41 healthy women aged 20-27 years. Twenty-one women of the study group were prescribed an oral contraceptive (30 microg ethynyl estradiol and 150 microg levonorgestrel) and 20 women of the control group a nonhormonal contraceptive or none. Biochemical markers of bone metabolism (bone-specific alkaline phosphatase, osteocalcin, deoxypyridinoline) and VDR genotype, using BsmI endonuclease, were determined. After 3 months in the study group, the BB genotype subgroup showed significantly decreased osteocalcin (p = 0.010), in the Bb genotype subgroup bone-specific alkaline phosphatase (p = 0.043) and osteocalcin (p = 0.006) decreased, and in the bb genotype subgroup no changes were observed. In the control group, there were no significant changes in markers of bone metabolism regarding VDR genotype. In conclusion, our study shows that in young women VDR gene polymorphism could influence bone metabolism during low-dose oral contraceptive use.
    Contraception 02/2003; 67(1):33-7. · 3.09 Impact Factor
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    ABSTRACT: The study was conducted to assess the GH-IGF-I axis in non-obese women with functional hyperandrogenism (FH). Eighteen FH women aged 18-35 yr with a body weight within 20% of ideal body weight and 10 weight-matched controls were included in the study. Basal serum GH, GH-binding protein (GHBP), IGF-I, IGF-binding protein-3 (IGFBP-3) levels were determined as well as GH levels during GHRH stimulation. In addition, basal serum androgens [free T (FT), delta4 and DHEAS], insulin and glucose levels were determined. The group of non-obese patients with FH differed from controls in GHBP (1.21+/-0.37 vs 0.93+/-0.25 nmol/l; p<0.05) and androgen levels (FT: 8.0+/-3.2 vs 1.9+/-1.2 pmol/l, p<0.001; delta4: 10.5+/-3.2 vs 5.9+/-2.1 nmol/l, p<0.001; DHEAS: 9.3+/-3.0 vs 5.1+/-1.8 micromol/l, p<0.001). GH (r=0.365; p<0.05) and IGF-I (r=0.508, p<0.01) serum levels were significantly correlated to serum DHEAS levels in a combined group of patients and controls. Our results support the suggestion that the GH-IGF-I axis plays an important role in the evolution of hormonal and metabolic derangement in non-obese FH women.
    Journal of endocrinological investigation 10/2002; 25(8):691-5. · 1.65 Impact Factor
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    B Arko, J Prezelj, R Komel, A Kocijancic, P Hudler, J Marc
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    ABSTRACT: Osteoprotegerin (OPG) is a recently discovered member of the TNF receptor superfamily that acts as an important paracrine regulator of bone remodeling. OPG knockout mice develop severe osteoporosis, whereas administration of OPG can prevent ovariectomy-induced bone loss. These findings implicate a role for OPG in the development of osteoporosis. In the present study, we screened the OPG gene promoter for sequence variations and examined their association with bone mineral density (BMD) in 103 osteoporotic postmenopausal women. Single-strand conformation polymorphism analysis followed by DNA sequencing revealed a presence of four nucleotide substitutions: 209 G-->A, 245 T-->G, 889 C-->T, and 950 T-->C. The frequencies of genotypes were as follows: GG (89.3%), GA (10.7%) for 209 G-->A polymorphism; TT (89.3%), TG (10.7%) for 245 T-->G polymorphism; and TT (25.2%), TC (53.4%), CC (21.4%) for 950 T-->C polymorphism. Substitution 889 C-->T was found in only two patients. Statistically significant association of genotypes with BMD at the lumbar spine (P = 0.005) was observed for 209 G-->A and 245 T-->G polymorphisms. Haplotype GATG was associated with lower BMD as compared with GGTT haplotype. Our results suggest that 209 G-->A and 245 T-->G polymorphisms in the OPG gene promoter may contribute to the genetic regulation of BMD.
    Journal of Clinical Endocrinology &amp Metabolism 10/2002; 87(9):4080-4. · 6.43 Impact Factor
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    ABSTRACT: Insulin resistance is a common characteristic of women with polycystic ovary syndrome (PCOS) who are known to differ in their in-vitro fertilization outcomes compared to non-PCOS patients. As insulin resistance can be found in a considerable proportion of normal individuals, we assessed its contribution to ovarian responsiveness and fertilization rate. 26 non-PCOS patients undergoing IVF for the first time were investigated. Insulin resistance was evaluated by using a euglycemic hyperinsulinemic clamp technique. According to multiple regression analysis insulin sensitivity, expressed as insulin stimulated glucose disposal rate, during euglycemic clamp (r = -0.81, p < 0.05 and r = -0.89; p < 0.01) and basal estradiol level (r = -0.54; p < 0.05 and r = -0.56; p < 0.05) appeared significant negative predictors of the number of fertilized oocytes and embryos, respectively. Furthermore, basal glucose level appeared independently as a significant positive predictor of the number of fertilized oocytes and the number of embryos. (r = 0.90; p < 0.01 and r = 0.96; p < 0.01 respectively). We conclude that blood glucose concentration and insulin resistance respectively are independent predictors of IVF outcome.
    Wiener klinische Wochenschrift 07/2002; 114(12):454-7. · 0.81 Impact Factor
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    ABSTRACT: Genetic factors play an important role in the pathogenesis of osteoporosis. The genes involved are, however, still largely unknown. In the present study, we have investigated whether sequence variations in the estrogen receptor beta (ERbeta) gene are associated with bone mineral density (BMD) and biochemical markers of bone turnover in 79 Slovenian postmenopausal women with osteoporosis. We also assessed the response by BMD and bone markers to antiresorptive therapy with bisphosphonate alendronate. All eight exons of ERbeta gene were amplified by polymerase chain reaction and screened for mutations by single-strand conformation polymorphism analysis. Potentially mutated samples were found only in exon 5 and sequence analysis identified the presence of a silent mutation in codon 328 with a nucleotide substitution GTG to GTA. For easier detection of this silent mutation, the RsaI restriction fragment length polymorphism analysis was developed. The frequencies of genotypes were as follows: Rr 5.1% and RR 94.9%. Between both genotypes, no significant differences in baseline lumbar spine and femoral neck BMD or in bone markers osteocalcin and deoxypyridinoline were observed. Similarly, no significant difference between RR and Rr genotypes in BMD or bone markers after 1 year of therapy was found. The increase in lumbar spine BMD after therapy was the only parameter that approached statistical significance (P=0.099). Patients with genotype Rr showed a smaller increase compared to those with RR. Our results suggest that RsaI polymorphism of ERbeta gene is probably not an important genetic determinant of BMD and does not significantly influence the responsiveness to alendronate therapy.
    The Journal of Steroid Biochemistry and Molecular Biology 07/2002; 81(2):147-52. · 3.98 Impact Factor
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    ABSTRACT: The cellular mechanisms for the insulin resistance in pregnancy and gestational diabetes mellitus are not known. The membrane protein plasma cell glycoprotein PC-1 has been identified as an inhibitor of insulin receptor tyrosine kinase activity and could have a role in insulin resistance. This study aimed to examine the effects of insulin on glucose transport and changes in insulin receptor tyrosine phosphorylation, IRS-1 and PC-1. Adipocytes were obtained either during elective cesarean section from three groups of subjects (Type II diabetic pregnant women ( n=6) women with gestational diabetes mellitus ( n=10) and pregnant women with normal glucose tolerance ( n=6) as pregnant control subjects) or during elective gynaecological surgery from non-pregnant ( n=6) control subjects. Insulin stimulated glucose transport was reduced by 50% in women with gestational diabetes mellitus and 70% in pregnant women with Type II diabetes, compared to the non-pregnant control subjects. After maximal insulin stimulation of adipocytes, IRTK phosphorylation was reduced by 29.5% in women with gestational diabetes mellitus and 44.5% in women with Type II diabetes, compared to the non-pregnant control subjects. We also found that IRS-1 phosphorylation was reduced by 32% and 48%, respectively. On the other hand, PC-1 content in adipocytes in women with gestational diabetes mellitus increased by 320% and 668% in Type II diabetic women, compared to the non-pregnant control subjects. Our results indicate that women with gestational diabetes mellitus and Type II diabetes have increased PC-1 content and suggest that this could contribute to lower phosphorylation levels of IRTK and IRS-1. Furthermore, these postreceptor defects in insulin signalling pathway are greater in both groups compared to the women with normal pregnancy. However, results from women with Type II diabetes show that pre-existing insulin resistance lead to an even greater deterioration of the signalling pathway.
    Diabetologia 05/2002; 45(4):502-8. · 6.49 Impact Factor
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    ABSTRACT: Heading Aims/hypothesis. The cellular mechanisms for the insulin resistance in pregnancy and gestational diabetes mellitus are not known. The membrane protein plasma cell glycoprotein PC-1 has been identified as an inhibitor of insulin receptor tyrosine kinase activity and could have a role in insulin resistance. This study aimed to examine the effects of insulin on glucose transport and changes in insulin receptor tyrosine phosphorylation, IRS-1 and PC-1. Methods. Adipocytes were obtained either during elective cesarean section from three groups of subjects (Type II diabetic pregnant women ( n=6) women with gestational diabetes mellitus ( n=10) and pregnant women with normal glucose tolerance ( n=6) as pregnant control subjects) or during elective gynaecological surgery from non-pregnant ( n=6) control subjects. Results. Insulin stimulated glucose transport was reduced by 50% in women with gestational diabetes mellitus and 70% in pregnant women with Type II diabetes, compared to the non-pregnant control subjects. After maximal insulin stimulation of adipocytes, IRTK phosphorylation was reduced by 29.5% in women with gestational diabetes mellitus and 44.5% in women with Type II diabetes, compared to the non-pregnant control subjects. We also found that IRS-1 phosphorylation was reduced by 32% and 48%, respectively. On the other hand, PC-1 content in adipocytes in women with gestational diabetes mellitus increased by 320% and 668% in Type II diabetic women, compared to the non-pregnant control subjects. Conclusions/interpretation. Our results indicate that women with gestational diabetes mellitus and Type II diabetes have increased PC-1 content and suggest that this could contribute to lower phosphorylation levels of IRTK and IRS-1. Furthermore, these postreceptor defects in insulin signalling pathway are greater in both groups compared to the women with normal pregnancy. However, results from women with Type II diabetes show that pre-existing insulin resistance lead to an even greater deterioration of the signalling pathway.
    Diabetologia 01/2002; 45(4):502-508. · 6.49 Impact Factor
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    S Jurada, J Marc, J Prezelj, A Kocijancic, R Komel
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    ABSTRACT: Estrogen receptor alpha (ER alpha) encoding gene is one of the candidate genes to be involved in the development of osteoporosis. Until now correlation between three ER gene polymorphisms (identified with PvuII, XbaI and BstUI) and bone mineral density (BMD) have been investigated. The results of these studies are contradictory. Thus the aim of our work was to search for new, yet unknown, and probably more informative polymorphism(s) of the ER alpha gene. For detection of mutations the whole coding region of the ER alpha gene was screened systematically. In a group of 85 late postmenopausal women all of the eight exons were amplified by polymerase chain reaction (PCR) and fragments were further analyzed by single-stranded conformation polymorphism (SSCP) analysis. Mutations were confirmed by direct DNA sequencing. In the whole coding region of the ER alpha gene two silent mutations in codon 87 and 325, respectively, were found. The silent mutation in codon 85 of exon 1 (GCG-->GCC; A87A) was described previously, as BstUI polymorphism. On the other side, the silent mutation in codon 325 (CCC-->CCG; P325P), located in exon 4, has not been analyzed so far in correlation with BMD. According to the distribution of genotypes CC:CG:GG=49.4:41.2:9.4, we can affirm the existence of genetic polymorphism in codon 325 in our population of late postmenopausal women. The mean femoral neck BMD, but not the lumbar spine BMD, was significantly lower (P=0.029) in the homozygous GG-women with CCG/CCG codon 325 as compared to the homozygous CC-women with the normal codon CCC/CCC. Our results suggest that codon 325 sequence polymorphism of the ER alpha gene might be one of the factors associated with low femoral neck BMD.
    The Journal of Steroid Biochemistry and Molecular Biology 07/2001; 78(1):15-20. · 3.98 Impact Factor

Publication Stats

432 Citations
110.36 Total Impact Points

Institutions

  • 2007
    • University Medical Centre Maribor
      • Department of Endocrinology and Diabetology
      Maribor, Mestna Obcina Maribor, Slovenia
  • 1999–2007
    • University of Ljubljana
      • • Faculty of Electrical Engineering
      • • Faculty of Pharmacy
      • • Faculty of Medicine
      Ljubljana, Ljubljana, Slovenia
  • 1988–2006
    • Ljubljana University Medical Centre
      • • Department of Endocrinology, Diabetes and Metabolic Diseases
      • • Department of Gynaecology
      Lubliano, Ljubljana, Slovenia
  • 1994
    • Slovenia Medical
      Maribor, Maribor, Slovenia