Minerva endocrinology最新文献

Background: Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors.

Methods: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR.

Results: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients.

Conclusions: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.

Introduction: To compare survival outcome among the patients with concurrent small cell lung cancer (SCLC) and diabetes mellitus (DM) using metformin or without metformin.

Evidence acquisition: A systematic literature search for relevant studies up to Oct 2020 was conducted. Outcome of the included studies included overall survival (OS) or disease-free survival (DFS). HR values were pooled to estimate the effect of metformin on survival outcomes.

Evidence synthesis: Six studies with 539 participants with both SCLC and diabetes were included in the analysis. The patients with metformin usage had significantly longer OS and DFS than those without metformin usage (OS: HR=0.72 [0.53-0.98], P=0.04; DFS: HR=0.59 [0.45-0.76], P<0.0001). The studies included were not significantly different in the two analyses by heterogeneity test. There was no obvious publication bias.

Conclusions: Metformin may improve survival among patients with concurrent SCLC and DM. Further investigations especially randomized control trials are warranted, especially among the patients who do not have diabetes.

Beside its mechanical roles in controlling posture and locomotion, skeletal muscle system, the largest insulin and steroid hormones target tissue, plays a key role in influencing thermoregulation, secondary sexual characteristics, hormones metabolism, and glucose uptake and storage, as well as energetic metabolism. Indeed, in addition to insulin, several hormones influence the skeletal muscle metabolism/function and/or are influenced by skeletal muscles activity (i.e., physical exercise). Particularly, steroid hormones play a key role in modulating many biological processes in muscles, essential for overall muscle's function and homeostasis, both at rest and during all physical activities (i.e., physical exercise, muscular work). Phosphodiesterase type 5 (PDE5) is the enzyme engaged to hydrolyze cyclic guanosine monophosphate (cGMP) in inactive 5'-GMP form. Therefore, through the inhibition of this enzyme, the intracellular level of cGMP increases, and the cGMP-related cellular responses are prolonged. Different drugs inhibiting PDE5 (PDE5i) exist, and the commercially available PDE5i are sildenafil, vardenafil, tadalafil, and avanafil. The PDE5i tadalafil may influence cellular physiology and endocrine-metabolic pathways in skeletal muscles and exerts its functions both by activating the cell signaling linked to the insulin-related metabolic pathways and modulating the endocrine responses, protein catabolism and hormone-related anabolism/catabolism during and after physical exercise-related stress. Based on recent in-vivo and in-vitro findings, in this narrative review the aim was to summarize the available evidence describing the interactions between the PDE5i tadalafil and steroid hormones in skeletal muscle tissue and physical exercise adaptation, focusing our interest on their possible synergistic or competitive action(s) on muscle metabolism and function.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are considered a new class antidiabetic agent, as well as lowering blood sugar, it has many positive effects. This study aimed to investigate the effects of SLGT2i on the gastric mucosa.

Methods: We investigated the effects of empagliflozin on indomethacin-induced gastritis using 48 male Wistar Albino rats. We performed histopathological evaluations of gastric mucosa tissue. And we studied the levels of serum disulfide, native thiol, total thiol, and ischemia modified albumin, disulfide/native thiol ratio (SSSH), native thiol/total thiol percent ratio (SH total SH), and disulfide/total thiol percent ratio (SS total SH).

Results: We found that empagliflozin increased mucin production in rat gastric mucosa. Besides, we observed milder inflammation findings and lower gastritis scores in the empagliflozin receiving groups than the placebo groups. Native thiol, total thiol, and disulfide levels were lower in the indomethacin-induced gastritis groups.

Conclusions: This study is the first to investigate the effect of empagliflozin on the gastrointestinal tract in a rat model. We concluded that empagliflozin increased mucin production and revealed positive effects in an indomethacin-induced gastritis model.

Background: Differences in epidemiological data from different geographical regions have made the prevalence of thyroid disease and thyroid cancer controversial. No previous study has investigated whether thyroid disease and thyroid cancer prevalence are higher in acromegalic patients than in the general population in Türkiye. The aim of this study is to determine the prevalence of thyroid disease and thyroid cancer in acromegaly and to compare it with the control group.

Methods: A total of 129 acromegalic patients (78 female, 51 male) and 247 control group patients (151 female, 96 male) were included in the study. Pituitary size, growth hormone (GH) and insulin-like growth factor (IGF)-1 levels in all patients with acromegaly and thyroid function tests, thyroid receptor autoantibody (TRAb), thyroid scintigraphy, thyroid ultrasonography (US), fine-needle aspiration cytology (FNAC) and histopathology findings after thyroidectomy were recorded.

Results: Thyroid lesions were present in 93 patients (72.1%) with acromegaly. While diffuse goiter (14.7%) and multinodular goiter (MNG) (47.3%) were significantly higher, Graves' disease (4.5%) was significantly lower in the acromegaly group compared to control group. The presence of thyroid lesions and thyroid nodules was significantly higher in patients with acromegaly (odds ratio 2.766; 95% CI 2.112-4.469, P<0.001 and OR 1.955; 95% CI 1.206-3.170, P=0.007). According to gender, the prevalence of thyroid lesions, MNG and thyroid cancer was significantly higher in female patients than in the control group. Thyroid cancer prevalence was found in 7% of acromegalic patients and the prevalence of thyroid cancer in the control group was 4.5%.

Conclusions: It remains controversial whether the risk of thyroid cancer is increased or not in patients with acromegaly. In this study, there is no significant difference in thyroid cancer between acromegaly and control group, but thyroid lesions are significantly more common in acromegaly. Also, more research is required to determine if thyroid lesions are more prevalent in females with acromegaly.

Background: Research findings indicate that neuropilin-1 plays a critical role in lipid metabolism and obesity-associated insulin resistance; on such a basis, the aim of this study was to explore the effects and working mechanism of neuropilin-1 inhibition on the non-alcoholic fatty liver (NAFLD) disease in high-fat-diet (HFD) induced obese mice.

Methods: Firstly, the pcDNA3.1-NRP-1 recombinant plasmid containing neuropilin-1 (NRP1) gene and NRP1 RNA interference plasmid shRNA-NRP1 were successfully constructed. A total of 36 C57BL/6 mice were randomly assigned to 6 groups, blank group, control group, pcDNA3.1 injection group, pcDNA3.1-NRP-1 injection group, pGenesil-1.1 injection group and shRNA-NRP1 injection group. Expression of phospho-PI3K, phospho-AKT, phospho-mTOR and neuropilin-1 in liver was measured as well as body and liver weight, blood glucose, serum transaminases and lipid levels of the mice.

Results: The weight and liver mass of HFD fed mice injected with pcDNA3.1-NRP-1 were significantly higher than those from the control group, but their body weight and liver mass decreased significantly after shRNA-NRP1 injection. The results also showed that neuropilin-1 expression can significantly influence the severity of hepatic steatosis in HFD fed mice, decreased serum FPG, LDL, AST, ALT levels and the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 mRNA. In addition, the Neuropilin-1 expression will also influence the p-PI3K, p-AKT and p-mTOR in mice.

Conclusions: This study concluded that the inhibition of neuropilin-1 could improve NAFLD disease by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the PI3K/AKT/mTOR signaling pathway.

Background: The endocannabinoid system is involved in the regulation of energy balance and ovarian function and may be implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The purpose of the present study is to determine anandamide (AEA) levels in PCOS patients and controls and to analyze its association with metabolic and hormonal disturbances in women with PCOS.

Methods: The study included 88 women - 58 patients with PCOS (25.9±5.2 years) and 30 healthy controls (27.6±5.2 years). Further, patients were divided into two subgroups according to their waist-to-hip ratio (WHR): android type PCOS (WHR≥0.85; N.=26) and gynoid type PCOS (WHR<0.85; N.=32). Detailed anthropometric measurements, hormonal and biochemical tests and pelvic ultrasound were obtained between the 3rd and 5th day of a menstrual cycle. AEA was examined by ELISA kits.

Results: Patients with PCOS and healthy controls did not differ in anthropometric, metabolic parameters, AEA, and sex hormone-binding globulin (SHBG) levels. The PCOS group had increased total testosterone, FAI, DHEAS, androstenedione, and 17-OH-progesterone levels (P<0.001) and elevated LH/FSH ratio (P=0.023). A negative correlation between AEA levels was found with glycaemia at 120 minutes (r=-0.304, P=0.020) and WHR (r=-0.266, P=0.044). In the subanalysis of patients, the gynoid type group had significantly higher levels of AEA than the android type PCOS (5.4 [2.3;8.8] vs. 2.5 [1.8;5.1]; P=0.020).

Conclusions: AEA did not differ between healthy women and patients, but a significant difference in its levels was found in PCOS patients divided according to their body constitution type.

Introduction: Our purpose was to review the scientific literature and collect information regarding clinical and technical parameters of different single- or multiphase CT protocols, their diagnostic performance and patient dose during parathyroid imaging.

Evidence acquisition: PubMed and Scopus databases were searched for studies investigating the diagnostic performance of CT in detecting parathyroid lesions and the corresponding patients' dose. The following information was retrieved for each article: CT system, number, combination and time interval between phases, scanning length, sensitivity, specificity, accuracy, positive and negative predictive values, contrast enhancement in Hounsfield Units (HUs), technical and exposure parameters, and dose indices. Fifty studies published during the last sixteen years (2005-2021) were reviewed.

Evidence synthesis: A large discrepancy in the number and combination of phases, as well as clinical and technical parameters of the CT protocols was indicated. The variations in patients' doses are mainly due to scanners' technology, number and combination of phases, the extent of scanning length, technical parameters (tube voltage, tube current modulation, pitch, reconstruction algorithms), and patient-related parameters. Technical parameters are not always adjusted appropriately to the clinical question or patient size. These variations indicate a large potential to optimize dose during parathyroid imaging without compromising diagnostic performance. The potential is to decrease the number of phases or use low tube voltage protocols, tube current modulation, iterative reconstruction, and reduce the scanning length during some phases.

Conclusions: The reporting results could inform researchers about the current status of CT parathyroid imaging and guide their future efforts to optimize both patients' dose and corresponding image quality.

Introduction: An association between glucagon-like peptide-1 receptor agonists (GLP1-RA) and risk of pancreatitis and pancreatic cancer has been suggested. Since its first description, several new trials (including three cardiovascular outcome trials) have been published, substantially increasing the available data set. This suggests the need for an update of the previous meta-analysis.

Evidence acquisition: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials, with duration ≥52 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. The endpoints were pancreatitis, pancreatic cancer reported as serious adverse events. Mantel-Haenszel Odds Ratio (MH-OR) with 95% confidence interval (95% CI) was calculated for all outcomes defined above, on an intention-to-treat basis.

Evidence synthesis: A total of 43 trials fulfilling inclusion criteria (all reporting data on pancreatitis and pancreatic cancer) was identified. GLP-1 RA showed no association with pancreatitis (MH-OR 1.24 [0.94, 1.64]; P=0.13) and pancreatic cancer (MH-OR 1.28 [0.87, 1.89]; P=0.20).

Conclusions: No clear evidence of risk for pancreatitis was observed, whereas data on pancreatic cancer are too scarce to draw any conclusion.