ACTA ENDOCRINOLOGICA (BUC)

Objective. One functional neuroendocrine tumor that causes hypoglycemia due to inappropriately high insulin production is an insulinoma. In rats, two genes coding for insulin, insulin 1 (Ins1) and insulin 2 (Ins2) are found on chromosome 1. Ins1 was produced from an Ins2 transcript, and it was inserted into the genome via an RNA-mediated duplication-transposition event, according to some structural feature analyses. Methods. In this study, the author has looked at how overexpression of the PTEN gene in the insulinoma cell line Rin- 5F affects the expression of the insulin genes, Ins 1 and Ins 2. Results. In the insulinoma cell line, overexpression of the PTEN gene boosts Ins2 gene mRNA expression but not Ins1 gene mRNA expression. It has been reported that PTEN upregulates insulin signaling by increasing insulin receptor substrate (IRS)-2 mRNA levels. Also, PTEN has been reported to be secreted in exosomes and thereafter, into extracellular space. Conclusions. The present study suggested that overexpression of PTEN might induce the increasing Ins 2 gene expression, one of the phosphorylated genes against the IRS-2 through the insulin/IGF-1 receptor. Our knowledge of the molecular pathways of PTEN relating the synthesis of insulin has been increased by the present study.

Many women with polycystic ovary syndrome (PCOS) also present with nonalcoholic fatty liver disease (NAFLD) secondary to obesity and/or insulin resistance. Assuming that fatty liver, by inducing impairments in steroid metabolism might contribute to characteristic hyperandrogenemia in women with PCOS, we studied a group of 44 women with PCOS and a control group of 20 women matched according to age, waist circumference and body mass index. In PCOS group, serum testosterone was significantly higher when the degree of lipid infiltration of the liver (ultrasonographically assessed) was higher (1.34?0.14 ng/mL in steatotic PCOS group vs. 0.72+0.1 ng/ml in non-steatotic PCOS group, p=0.001). Our study offers an additional explanation for high testosterone levels in women with PCOS, implying liver in the pathogenic chain that leads to excess androgen.

Objective. ARMC5 mutations are responsible for the development of primary bilateral macronodular adrenal hyperplasia (PBMAH). In this study, we aimed to report a novel ARMC5 germline variant in a PBMAH patient family. Method. CT examination and dexamethasone suppression test (DST) were used in the diagnosis of PBMAH. Sanger sequencing was used to validate the familial heredity. For the novel variant, protein predictive analysis was performed to study the changes of secondary and tertiary structures and hydrophobicity. Results. A 45 years old male (proband, III-1) was diagnosed as PBMAH. Whole-exome sequencing (WES) was performed, finding one mutation: c.719_ 724dup, p Arg240_ Pro241dup. Sanger sequencing showed the II-2, III-1, IV-1 with heterozygous gene, confirming the familial heredity. For protein predictive analysis, the predicted secondary structure of variants has one alpha–helix structure incomplete compared with normal ARMC5. The tertiary structure could draw the same conclusion, that hydrophobicity decreases after mutation. Conclusion. We reported a new-found ARMC5 germline variant in PBMAH using WES and protein predictive analysis. With the help of WES, early diagnosis of PBMAH could help variant carriers to prevent the occurrence of cancer by lifetime follow-up.

Aim. Diabetic macular oedema (DME) can develop at all stages of diabetic retinopathy, causing visual impairment and blindness. Modern diets are high in advanced glycation end products (dAGEs), derived from processing methods, exerting a pivotal role in promoting diabetic retinopathy risk. In present study, we investigate the relationship between dietary and serum levels of AGEs and DME in type 2 diabetic subjects. Methods. This case-control study was conducted between July 2018 and February 2019 on 50 case subjects with DME and 40 healthy controls without DM without DME. The sociodemographic characteristics, nutritional status, and anthropometric measurements were evaluated. The advanced glycation end products (AGEs) and receptor for AGEs (sRAGE) levels in serum were analysed. Results. The AGEs levels of the DME group were higher than in the control group (p <0.05). sRAGE levels were higher in the DME group, but not statistically significant (p >0.05). The dietary intake of AGEs was higher in the DME group (p <0.05). It was found that an increase in neck circumference increased the risk of DME (p <0.001). Conclusion. A positive correlation was found between DME and AGEs, dAGE, neck circumference, and waist circumference. For the validity of these results, studies, including controlled nutrition interventions, are needed.

The novel coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on antenatal care, forcing authorities to consider some medical services unessential in the pursuit of avoiding the valid risk of patient contamination. The oral glucose tolerance test (OGTT) has been in some cases overlooked for screening in pregnancy, with potential detrimental consequences in terms of not diagnosing and treating gestational diabetes mellitus (GDM). The number of tests has dropped by 35% in 2020 in our hospital. We make a plea for resuming OGTT at 24-28 weeks gestation at least for women considered at high risk.

Objective. Gestational diabetes mellitus (GDM) is a common endocrine complication in pregnancy. There are few risk factors that clearly correlate with GDM. Fibroblast growth factor 21 (FGF21) is a metabolic hormone that can regulate glucose metabolism. It has been recognized that serum levels of FGF21 are significantly increased in diabetes and insulin resistance states. The objective of this study was to determine the serum FGF21 levels in women with GDM compared with non-GDM women and its correlation with insulin resistance. Methods. Thirty GDM patients and 60 healthy pregnant controls that matched for maternal and gestational age were selected. Women with previous history of GDM, hypertension, polycystic ovary syndrome, renal or liver failure and drug consumption with effects on glucose or insulin levels were excluded. FGF21 was determined and correlated with biochemical parameters of glucose metabolism and insulin resistance. Results. FGF21 concentration was significantly higher in GDM (264.5±196.2 ng/L) as compared with control groups (59.1±36.5ng/L). Correlation of FGF21 with insulin resistance was not significant. A cut-off 82.07 ng/L of FGF21 had sensitivity of 100% and specificity of 85% for prediction of GDM. Conclusion. FGF21 is increased in GDM and it is independent of insulin resistance. We suggest that FGF21 resistance could be directly involved in pathophysiology of GDM.

Introduction. McCune-Albright syndrome (MAS) is a noninherited, genetic condition defined by the clinical triad: polyostotic fibrous dysplasia (FD), café-aulait skin spots and different hyper functioning endocrinopathies. Case presentation. The patient, a 39-year-old female previously diagnosed with MAS, presented with severe, left-sided skeletal pain and accentuated asymmetrical facial features. Although there were no clinical signs (except type II diabetes) the hormonal dosages revealed GH hypersecretion and ACTH-independent hypercortisolism. The modified bone anatomy rendered the surgical adenomectomy impossible, whereas radiotherapy was not an option due to the increased risk of sarcomatous transformation of FD; therefore somatostatin analogues were used. Cushing syndrome was cured by left adrenalectomy. For the facial dysmorphism, surgical cure was proposed. CT revealed a pituitary microadenoma, severe craniofacial hyperostosis and left-side macronodular adrenal hyperplasia. Conclusion. We report the case of an adult female with MAS associating both acromegaly and Cushing syndrome, the MAS-Cushing syndrome association having been identified only in children up to present. The setting of a therapeutic strategy in these cases is difficult determined by the multiple concomitant tissue damage and by the limited number of therapeutic options available, not only for acromegaly, but also for pain management and the cure of bone deformities.

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Objectives. To assess the effects of electroacupuncture (EA) at the Zusanli (ST36), Guanyuan (CV4), Zhongwan (CV12), and Fenglong (ST40) acupoints on sirtuin 1 (SIRT1) and glucose transporter type 4 (GLUT4) expression in high-fat diet (HFD)-induced insulin-resistant (IR) rats. Methods. Wistar rats were divided into normal control (NC), HFD, and HFD+EA groups. NC rats were fed a standard chow diet and did not receive EA. After being fed an HFD for eight weeks, rats in the HFD+EA group received EA at 2 Hz five times a week for eight weeks. Rats in the HFD group did not receive EA. Results. In HFD-induced IR rats, EA inhibited body weight increase and water intake, which were observed in HFD rats. EA had no effect on fasting blood glucose and postprandial blood sugar levels. Intraperitoneal insulin tolerance testing revealed that EA enhanced insulin sensitivity in HFD-induced IR rats. Compared with NC rats, SIRT1 and GLUT4 were downregulated in the quadriceps femoris of HFD-fed rats but were increased after eight weeks of EA stimulation. Conclusions. EA enhanced HFD-induced insulin resistance by activating SIRT1 and GLUT4 in the quadriceps femoris. These results provide powerful evidence supporting the beneficial effects of EA on HFD-induced insulin resistance.