Vitamin D supplementation alleviates diabetic complications by increasing the amount of irisin in testicular tissues and blood of rats with experimental diabetes.

OBJECTIVE: Diabetes is an important endocrinological disease that has an increasing incidence in the world and affects all biological tissues including testicles. Therefore, this study aimed to reveal the histological and biochemical effects of vitamin D on irisin, apoptosis, total antioxidant status (TAS), and total oxidant status (TOS) in testicular tissues of rats with experimental diabetes. MATERIALS AND METHODS: 41 male Wistar rats, 8-10 weeks old, weighing between 200-220 g, were included in the study as the following groups: control group (n=7; no treatment), sham group [only sodium citrate buffer (SCB)] [n=7; single dose 0.1 Molar (M) SCB given intraperitoneally (i.p)], vitamin D group (n=7; 50 IU/day given orally), diabetes group [n=10; single dose 50 mg/kg Streptozotocin (STZ) dissolved in 0.1 M SCB and given i.p (tail vein blood glucose level above 250 mg/dl after 72 hours)] and diabetes+vitamin D group [n=10, single dose 50 mg/kg STZ, dissolved in 0.1 M SCB and given i.p (tail vein blood glucose level above 250 mg/dl after 72 hours) and when diabetes occurs, oral vitamin D administration of 50 IU/day)]. At the end of the 8 weeks experiment, blood was drawn from the tail vein of all rats, they were sacrificed and testicular tissues were taken. While the amount of irisin in the blood and testicular tissue supernatants was analyzed with the Enzyme-Linked Immunosorbent Assay (ELISA) method, TAS and TOS measurements were analyzed with the REL method, testicular tissues were analyzed histopathologically, immunohistochemically, and with the TUNEL method. RESULTS: When the diabetes group was compared with the control and sham groups, it was reported that the amounts of blood and tissue supernatant irisin and TAS significantly decreased and the TOS was significantly increased; a statistically significant increase in irisin and TAS of blood and tissue supernatants and a significant decrease in TOS were detected when diabetes+vitamin D and diabetes groups were compared among themselves. Similar results were obtained in the immunohistochemical studies. Tissue expressions of irisin decreased in the diabetes group compared to the control and sham groups, while the application of vitamin D increased the tissue expressions of irisin. Additionally, when the numbers of apoptotic cells were compared, it was reported that apoptotic cells in the diabetes group increased significantly compared to the control and sham groups, and vitamin D administration significantly decreased the number of apoptotic cells. CONCLUSIONS: Taken together, vitamin D administration to diabetic rats decreased the number of apoptotic cells and increased the amount of irisin. Vitamin D had an effective role in maintaining the physiological integrity of rat testicular tissues, so vitamin D may be a potent agent to be used in the treatment of diabetes in the future.

Basal blood concentrations of some orexigenic and anorexigenic hormones in obese and nonobese individuals according to blood groups.

OBJECTIVE: Obesity is a serious public health problem associated with excessive food intake. Regulation of food intake in highly organized organisms is under the control of a large number of orexigenic and anorexigenic molecules. Therefore, the main purpose of this study has been to determine the relationship between obesity and some of the circulating orexigenic and anorexigenic peptides that have a role in appetite control and to determine whether the concentrations of these molecules differ according to blood groups. PATIENTS AND METHODS: The study included 400 individuals of whom 100 were obese women, 100 obese men, 100 healthy men and 100 healthy women. Obese women and men were divided into 4 groups, according to their blood groups. In the control group, healthy women and healthy men were similarly divided into 4 blood groups. Each blood group within the groups, therefore, had 25 participants. RESULTS: When leptin, nesfatin-1, obestatin and neuropeptide-Y, ghrelin and galanin levels of the control group and obese participants were compared, regardless of blood groups, leptin, nesfatin-1, obestatin and neuropeptide-Y were significantly higher, whereas only the ghrelin levels were significantly lower in obese patients. When the amounts of these hormones were measured according to gender, the situation was similar. When leptin, nesfatin-1, obestatin and neuropeptide-Y values of the control and obese participants' blood groups were compared with each other; these hormones were high in all blood groups; however, leptin levels in A blood group, nesfatin-1 levels in AB and O blood group, obestatin levels in AB blood group, neuropeptide-Y levels in A, B, AB blood groups were significantly higher. When the ghrelin levels of the blood groups in the control group and obese participants were compared, it was only significantly lower in the AB blood group. The ghrelin levels in the other blood groups of the obese individuals were again low, but not significantly so. When the distribution of hormones according to gender was evaluated, a situation parallel to the above results was recorded. CONCLUSIONS: Leptin, nesfatin-1, obestatin and neuropeptide-Y and galanin levels of obese individuals were significantly higher than the control values, whereas the ghrelin values were significantly lower regardless of blood groups. Also, these hormones in blood partly varied with ABO blood groups. These different concentrations of hormones in ABO blood groups might be related with stimulation or suppression of appetite in human. However, further studies in other ethnic groups are needed to confirm these results.

Molecular communication between Apelin-13, Apelin-36, Elabela, and nitric oxide in gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a type of diabetes that affects from 3.8% to 6.9% of pregnancies worldwide, causing significant mortality and unfavorable obstetric outcomes, such as delivery trauma and macrosomia risk. The fundamental processes of this metabolic disorder that first appeared during pregnancy are still unknown. Tissue hormones, particularly adipokines, have aided in understanding the pathophysiology of numerous disorders in recent years. This study aims to determine if Apelin-13 (APLN-13), Apelin-36 (APLN-36), Elabela (ELA), and nitric oxide (NO) molecules have all a part in the pathophysiology of GDM. PATIENTS AND METHODS: The study included 30 pregnant control women and 30 pregnant women who had been diagnosed with GDM in the second trimester and whose body mass index and age were compatible with each other. Blood samples were collected from 60 participants during the second trimester (30 control pregnant women and 30 GDM pregnant women) and postpartum (17 controls vs. 14 GDM). In these blood samples, the amounts of APLN-13, APLN-36, ELA, and NO were studied using the ELISA method. In addition, the participants' glucose, lipid profiles, and other parameters were obtained from the hospital record files. At postpartum, 29 pregnant women (13 control and 16 pregnant women with GDM) dropped out of the study without explanation. RESULTS: In the second trimester and postpartum plasma of mothers with GDM, APLN-13, APLN-36, NO, and ELA molecules were found to be significantly higher (< 0.05), compared to those of the control mothers, while APLN-13, APLN-36, NO values were significantly lower (0.05). While APLN-13, APLN-36, NO amounts in mothers with GDM were positively correlated with glucose amounts, they were negatively correlated with ELA amounts. Similarly, the triglyceride amounts in mothers with GDM were positively correlated with APLN-13, APLN-36 and NO, while they were negatively correlated with the ELA amounts. Due to gestational diabetes, APLN-13, APLN-36, NO, glucose, and triglyceride increased, and ELA decreased. CONCLUSIONS: It is predicted that the glucose increase in GDM is because Apelins reduce glucose transport to erythrocytes by inhibiting the sodium-dependent glucose transporter (SGLT) and that the increase in triglyceride and NO may be associated with high glucose levels in GDM. As a result, we believe that the above-mentioned chemicals may cause GDM Pathology by triggering one another.

Laboratory evidence on a direct correlation between acute central serous chorioretinopathy and tenascin C, metalloprotein 1, BAX, BCL2, subfatin and asprosin.

PURPOSE: Central serous chorioretinopathy (CSCR) is an eye disease of unknown etiology that presents with reduced visual acuity, choroidal thickening (distance between Bruch's membrane and the chorioscleral border), and subretinal fluid leakage. In the present study, the goal was to investigate the role of the interrelated tenascin C, metalloprotein-1, BAX, BCL2, subfatin and asprosin molecules in the pathogenesis of CSCR. METHOD: Thirty CSCR patients and 30 controls were included. CSCR was diagnosed by optical coherence tomography imaging. A 5mL blood sample was collected from all participants after overnight fasting. Compounds in the blood samples were studied with the Enzyme-Linked Immunosorbent Assay (ELISA) method. RESULTS: Patients with CSCR were found to have macular thickening (P: 0.08) and statistically significantly reduced visual acuity (P: 0.034) compared to controls. With regard to serum parameters, there were statistically significant increases in tenascin C, metalloprotein-1, BAX, BCL2, subfatin and asprosin levels compared to controls. We found a positive correlation between macular thickness and tenascin C (r+0.670, P<0.001), metaloprotein-1 (r+0.714, P<0.001), BAX, BCL2 (r+0.771, P<0.001), subfatin and asprosin levels and a negative correlation between visual acuity and tenascin C (r+0.605 P<0.001), metaloprotein-1 (r+0.704, P<0.001), BAX, BCL2 (r+0.738, P<0.001), subfatin and asprosin levels. CONCLUSION: The molecules studied herein were negatively correlated with visual acuity and positively correlated with macular thickness, suggesting that these molecules might have a role in the pathogenesis of CSCR. Thus, we predict that these molecules could be new candidates for the diagnosis and follow-up of CSCR in the future.

Effects of iloprost and sildenafil treatment on elabela, apelin-13, nitric oxide, and total antioxidant and total oxidant status in experimental enzyme-positive acute coronary syndrome in rats.

Despite significant advances in medicine, mortality due to cardiovascular disease is not yet preventable. We investigated the amounts of elabela (ELA) and apelin, synthesized by cardiomyocytes, and changes of these compounds in cardiac tissue and circulation after administration of iloprost (ILO) and sildenafil (SIL) in rats with induced myocardial ischemia (MI). We also investigated a connection with circulating troponin-I, creatine kinase (CK), creatine kinase-myocardial band (CK-MB) and nitric oxide (NO), and total anti-oxidant (TAS)/total oxidant status (TOS). We established eight study groups of five rats each. Group 1, sham, was given only physiologic serum; group 2, ILO; group 3, SIL; group 4, ILO + SIL; group 5, MI; group 6, MI + ILO; group 7, MI + SIL; group 8, MI + ILO + SIL. Troponin-I, CK, CK-MB and TAS-TOS were investigated using an autoanalyzer. NO, ELA and apelin were analyzed by ELISA. Tissue apelin and ELA expressions and localizations were determined by immunohistochemistry. The MI group compared to the control (sham) group showed that ELA, apelin, troponin-I, CK, CK-MB, NO and TOS levels were elevated significantly. Concentrations of these factors increased in MI, but decreased after ILO and SIL administration. The largest decrease of TOS was identified in the ILO + SIL group. ELA and apelin may be novel indicators of MI and administration of ILO and SIL, individually or together, may be useful for treating MI.

Immunostaining characteristics of irisin in benign and malignant renal cancers.

We investigated the expression of irisin in renal cancers using immunocytochemistry. Irisin has been reported to exhibit anticancer properties. The study groups consisted of 22 cases each of control renal tissue, oncocytoma, chromophobe renal cell carcinoma (RCC), clear cell RCC (Fuhrman nuclear grades 1, 2, 3 and 4) and papillary RCC. We evaluated 10 slides for each of 176 cases. Slides were immunostained for irisin and histoscores were calculated for the prevalence and strength of immunostaining. Fuhrman nuclear grade 1, 2, 3 clear cell RCC and papillary RCC exhibited no irisin immunoreactivity. Irisin immunoreactivity was observed in some Fuhrman nuclear grade 4 RCCs. We found a significant decrease in irisin staining in chromophobe RCC compared to the control. Immunoreactivity in the oncocytoma tissue was comparable to the control group. Irisin immunoreactivity in chromophobe RCC decreased and no immunoreactivity was observed in Fuhrman nuclear grade 1, 2, 3 clear cell RCC and papillary RCC. Immunistochemical screening of irisin in renal oncocytomas and renal cancers may be useful for differential diagnosis.

Identification of immunohistochemical localization of irisin in the dwarf hamster (Phodopus roborovskii) tissues.

Irisin is mainly secreted by heart and skeletal muscle cells. It is an exercise-induced protein that converts white adipose tissue to brown. Increased irisin expression was lead to weight loss and improved glucose tolerance. We investigated irisin immunoreactivity in various tissues of the dwarf hamsters (Phodopus roborovskii). Tissues were processed, embedded in paraffin, sectioned at 5 µm and stained immunohistochemically for irisin. In the retina, irisin was found almost all layers, except outer nuclear layer. Also, irisin immunoreactivity was observed in the skin, cornea, striated muscle, parotid gland, tongue, oesophagus, stomach and small intestine. The findings from this study support the notion that skeletal muscle is not the primary source of irisin.

Immunohistochemical localization of irisin in mole rats (Spalax leucodon).

Irisin was first identified in skeletal muscle cells. It is an exercise protein that is secreted into the circulation; it causes conversion of white adipose tissue to brown adipose tissue. We investigated irisin immunoreactivity in mole rat (Spalax leucodon) tissues. We examined cerebellum, pituitary, heart, liver, pancreas, spleen, uterus, kidney and striated muscle in female adult mole rats. Tissues were processed, embedded in paraffin, sectioned at 5 µm and stained immunohistochemically for irisin. Irisin immunostaining was detected in the cytoplasm of stained cells; the cytoplasm of Purkinje cells was unstained. We found that irisin may be synthesized in many tissues. The function of locally synthesized irisin currently is unknown.

Immunohistochemical localization of irisin in skin, eye, and thyroid and pineal glands of the crested porcupine (Hystrix cristata).

Irisin was first identified in muscle cells. We detected irisin immunoreactivity in various organs of the crested porcupine (Hystrix cristata). In the epidermis, irisin immunoreactivity was localized mainly in stratum basale, stratum spinosum and stratum granulosum layers; immunoreactivity was not observed in the stratum corneum. In the dermis, irisin was found in the external and internal root sheath, cortex and medulla of hair follicles, and in sebaceous glands. Irisin immunoreactivity was found in the neural retina and skeletal muscle fibers associated with the eye. The pineal and thyroid glands also exhibited irisin immunoreactivity.