ACTA ENDOCRINOLOGICA (BUC)

Accumulating evidence indicates that induction of inducible nitric oxide (NO) synthase and the subsequent NO production may be involved in the pathogenesis of insulin resistance. However the role of NO on insulin action of glucose uptake in skeletal muscle is not clearly understood. We hypothesized that NO does not impair insulin action of glucose uptake in skeletal muscle. To test this hypothesis, isolated rat epitrochlearis muscles were incubated in the presence or absence of sodium nitroprusside (SNP), a NO donor, with or without insulin, followed by measurement of glucose uptake. A low concentration of SNP (0.1 mM) did not stimulate glucose uptake, whereas a high concentration of SNP (10 mM) caused a large increase in glucose uptake in the absence of insulin (basal: 1.08?0.13; 0.1mM SNP: 1.32?0.11; 10 mM SNP:3.85?0.32 μmol/ml/20 min) When muscles were incubated in the presence of 0.1 mM SNP with insulin, the glucose uptake was not significantly different than that induced by insulin alone (insulin: 3.54?0.34; insulin+0.1mM SNP: 4.42?0.37 μmol/ml/20 min). In the presence of 10 mM SNP with insulin, the combined effect on glucose uptake was greater than that induced by insulin alone (insulin+10mM SNP: 6.32 ? 0.31 μmol/ml/20 min). The calculation of net increase of insulinstimulated glucose uptake (SNP+insulin minus SNP alone) clearly demonstrated that insulin action of glucose uptake was not impaired by SNP. Furthermore, wortmannin did not inhibit SNPstimulated glucose uptake and NG-monomethyl-L-arginine, a NO synthase (NOS) inhibitor, also did not block insulin-stimulated glucose uptake, indicating no interaction between NO signaling and insulin signaling in glucose uptake mechanisms. These results strongly suggest that NO does not induce insulin resistance of glucose uptake in isolated rat epitrochlearis muscle.

Objectives. The aim of this study was to evaluate serum levels of interleukin (IL)-8 in pre- and postmenopausal women and in patients with surgically-induced menopause, and the relationship between IL-8 and vasomotor symptoms. Material and Method. 175 women were enrolled and were divided into 5 groups (I – Fertile women; II – Pre- and perimenopausal women; III – Postmenopausal women; IV – Surgically-induced menopause; V – Chronic inflammation). Multiplex cytokine kits were used to evaluate serum levels of interleukin-8. We determined the serum levels of the follicle stimulating hormone, of the luteinizing hormone, 17β-estradiol, progesterone, dehydroepiandrosterone and dehydroepiandrosterone sulfate using sandwich ELISA. The severity of the vasomotor symptoms was evaluated according to FDA guidelines. Results. Serum concentration of IL-8 in women with natural menopause (233.0±226.5 pg/ml; p<0.001) and in women with surgically-induced menopause (148.0±162.0 pg/ml; p=0.045) is significantly higher than in women of reproductive age (84.88±82.32 pg/ml). Serum levels of IL-8 in premenopausal women, postmenopausal women, and in women with surgically-induced menopause, respectively, with severe and moderate hot flashes, on one hand (174.8±90.94 pg/ml, 369.3±194.2 pg/ml, respectively 274.1±146.3 pg/ml), is significantly higher than in women without vasomotor symptoms or with mild hot flashes, on the other hand (19.97±22.15 pg/ml, 28.66±35.72 pg/ml, respectively 28.94±37.68 pg/ml; p<0.001). Serum levels of IL-8 are significantly higher in women of reproductive age with chronic inflammatory pathology (152.3±121.0 pg/ml) than in women without such pathology (84.88±82.32 pg/ml; p=0.02). Conclusions. IL-8 is significantly higher in postmenopausal women with vasomotor symptoms than in women without vasomotor symptoms. In the postmenopausal group, the serum levels of IL-8 are similar to those in women with chronic inflammatory pathology. IL-8 could be a key factor in occurrence of hot flashes in menopause and could be associated with peripheral vasodilatation in these women.

Context. Oral anti-diabetic drugs (OADs) are leading option for treatment of type 2 diabetes (T2D). However, availability of OADs are limited in the presence of renal impairment (RI). Objective. In this study, we examined the efficacy of repaglinide, which is mainly metabolized and excreted via non-renal route, in patients with T2D and severe RI that consists mainly of chronic kidney disease (CKD) stage 4. Design, Subjects and Methods. This was an open label, single arm, interventional study by repaglinide monotherapy. The primary efficacy end point was HbA1c change from baseline to week 12. Results. Repaglinide treatment significantly reduced HbA1c levels from 7.7 ± 0.7% to 6.1 ± 0.3% (p<0.001) in 9 patients with severe RI (mean estimated glomerular filtration rate was 26.4 ± 7.5 mL/min/1.73m2). Focusing on 4 patients who received DPP-4 inhibitor monotherapy at enrolment, switching to repaglinide also significantly improved HbA1c levels. No hypoglycemic symptoms or severe hypoglycemia was reported in patients who completed the period of 12 weeks. Conclusions. We demonstrated the efficacy of repaglinide in patients with T2D and severe RI. In case that DPP-4 inhibitors are not enough to achieve targeted range of glycemic control, repaglinide is another good candidate.

Primary adrenal tumors include a broad variety of lesions, from nonfunctioning incidentalomas to secreting adrenocortical adenomas including Aldosteronism, Cushing or androgen secreting lesions. Primary tumors can occur either in the cortex or the medulla of the adrenal glands, having different histopathological features and also different clinical appearances and treatment approaches. In addition, the adrenal glands can become distant metastatic sites of numerous primary malignancies. The first line of treatment in a broad variety of cases is surgery. After pathology results, in selected cases, apart the oncologic approach, radiotherapy could be an important therapeutic tool. In this paper we will discuss the role of radiotherapy in the treatment of adrenal gland lesions.

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Introduction. Leprechaunism is a rare autosomal recessive condition characterized by dysmorhic features, growth failure and disordered glucose homeostasis. Case report. A term infant was born to a first cousin, who previously lost a baby with Leprechaunism. Pregnancy and delivery were uneventful. Birth weight, length and head circumference were all below the third centile. Clinical examination at birth reveals large low set ears, depressed nasal bridge, gingival hyperplasia, prominent nipples, umbilical hernia, lipodystrophy, hypertrichosis, and wrinkled loose skin. Examination of the genitalia showed a prominent phallus, posterior fusion of the labioscrotal folds and no palpable gonads. A clinical diagnosis of Leprechaunism was made based on the family history and the clinical phenotype. In addition to the presence of ambiguous genitalia, management of this infant was complicated by poor glycemic control with frequent hyper and hypoglycemic episodes. Insulin was inappropriately high (1626.1 mU/mL, normal 3-17 Mu/mL) when glucose was relatively low (3.2 mmol/L) indicating insulin resistance. ACTH stimulation test confirmed an intact adrenal function with normal 17 hydroxyprogesterone and cortisol. Testosterone and adrenal androgens were normal. Chromosomal study showed 46 XX and MRI abdomen revealed normal pancreas and internal female organs. Accordingly, this infant was assigned as a female. Severe hyper and hypoglycemic episodes responded to introduction of frequent nasogastric formula milk feeding together with insulin glargine. Glycemic control improved with glycated hemoglobin of 8%. Conclusion. This case report illustrates a management challenge of a newborn infant with Leprechaunism, ambiguous genitalia and poor glycemic control and discuss treatment options.

Background. Diabetes mellitus has been associated with many different musculoskeletal system problems. Objective. This study aims to show the prevalence of musculoskeletal disorders in patients with diabetes and to reveal their relationship to the metabolic parameters and microvascular complications. Methods. Seven hundred two diabetic patients who consecutively applied to our clinic between March 2017 and February 2018 were included in this prospective crosssectional study. The relationship of the musculoskeletal disorders including carpal tunnel syndrome, Dupuytren’s contracture, adhesive capsulitis, flexor tenosynovitis, limited joint mobility syndrome, Charcot arthropathy, diabetic foot and gout to the patients’ age, gender, type of diabetes, duration of diabetes, metabolic parameters, and microvascular complications were evaluated. Results. Musculoskeletal system disorders were detected in 45.9% (n = 322) of the 702 diabetic patients evaluated in our study. The most common disorders were carpal tunnel syndrome 17.7% (n = 124), Dupuytren’s contracture 14.4% (n = 101), and adhesive capsulitis 13.8% (n = 97). A statistically significant relationship of the HbA1c level with Dupuytren’s contracture, carpal tunnel syndrome, and adhesive capsulitis was detected (p<0.05). Conclusions. Patients’ age, duration of diabetes, HbA1c level, and presence of microvascular complications are associated with musculoskeletal disorders in this population.

Background. Adiponectin, vaspin and leptin are only a few of these numerous adipocytokines. Little is known about the behavior of adipocytokines and how adipose tissue metabolism is affected in this Type 1 DM model. In this study we investigated the serum levels of adiponectin, leptin, vaspin in streptozotocin(STZ) induced diabetic rats. Material and methods. Twelve Spraque Dawley albino rats were included in the study. The animals were divided into two groups. The first group was diabetic (D) (n: 6) and 60mg / kg STZ was administered intraperitoneally (i.p.) to these rats. The second group was the non-diabetic control (ND) group (n: 6). All the animals were euthanized by cervical dislocation. Quantification of vaspin, Adiponectin, leptin in serum was performed using the ELISA kit. Results. Adiponectin, vaspin levels of diabetic group were found to be statistically lower than of control group (p<0.05). Leptin levels were significantly higher in the diabetic group (P<0.05). Conclusion. There is a need for new researches that can explain the relationship between Vaspin, Leptin and Adiponectin and Type 1 diabetes. New studies in this area will open new horizons for the identification of new biomarkers in the diagnosis and treatment of Type 1 diabetes.

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Objective. Estrogen receptor alpha (ESR1) polymorphisms (XbaI and PvuII) and vitamin D receptor (VDR) polymorphisms (FokI, BsmI, ApaI and TaqI) are the most frequently studied regarding the correlations with the infertility in males, but the results are controversial. The purpose of this study is to evaluate possible correlations between hormonal markers, VDR and ESR1 genotypes and semen analysis, in order to bring new data for a better understanding of male infertility. Subjects and Methods. 42 infertile men and 28 controls were enrolled. The polymorphisms of VDR gene (ApaI, TaqI, BsmI and FokI) and ESR1 (XbaI and PvuII) were performed by PCR-RFLP, along with hormonal markers. Results. An important correlation between PvuII polymorphism and infertility status was revealed. A significant difference between control and infertility group regarding the presence of BsmI (A>G) and ApaI (G>T) polymorphisms was observed in infertile group, prolactin and DHEA were found to correlate significantly statistic with BsmI GG genotype, whereas ApaI AA genotype correlates with prolactin and SHBG levels. Conclusions. By a multivariate analysis, we demonstrated a cumulative effect of some genetic variants in the hormonal status of infertile patients. Therefore, we show that specific genetic variants of ESR1 and VDR genes may jointly influence human spermatogenesis.