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Item Evaluation of electrodermal activity in diabetic rats treated with vildagliptin and metformin(Başkent Üniversitesi Sağlık Bİlimleri Enstitüsü, 2022) Muftah Shawesh, Muftah Mohamed; Yiğit, Ayşe ArzuElectrodermal activity (EDA) is the measurement of the electrical conductivity of skin, which indicates the activation of sympathetically innervated eccrine sweat glands. Thus, sympathetic system activity that innervates eccrine sweat glands. In our study, it was aimed to evaluate electrodermal activity and thus changes in sympathetic activity in diabetic rats treated with vildagliptin, metformin and metformin+vildagliptin combination. 50 male rats were used in this study. Rats were divided into control (n=10) and experimental groups (n=40). Forty animals in experimental group were injected with 45 mg/kg streptozotocin as a single dose intraperitoneally. After 3 days, animals whose blood glucose level exceeded 250 mg/dl were considered as diabetic. Rats were divided into 4 groups as diabetes, vildagliptin, metformin and metformin+vildagliptin. Vildagliptin (50 mg/kg), metformin (500 mg/kg) and 500 mg/kg metformin+50 mg/kg vildagliptin were administered by gavage for 15 days. After that blood glucose were be measured again end of the 15 days and seeing that diabetes continues, tonic activity was recorded before sound stimulus, and phasic skin conductivity level (SCR) was recorded in response to the auditory stimulus by using Biopac MP35 device. Differences between groups were determined by one-way Anova test. Tukey test was used to determine the significance between the groups. P<0.05 was considered significant. Both tonic SCL and phasic SCR were higher (p<0.001) in diabetic groups than the control group. These findings might explain the increase in the sympathetic activity in diabetic groups. In additiona, the blood glucose levels of the metformin and vildagliptin groups were lower than the diabetic group. Intrestingly, the metformin+vildagliptin group had a lower tonic SCL than the other experimental groups, whereas the metformin group had a less phasic SCR than the diabetes group (p <0.0001). Peak number of vildagliptin and metformin+vildagliptin groups decreased in tonic recording compared to diabetic group (p<0.0001, p<0.01 respectively). Our study, the fact that diabetic drugs caused a decrease in SCL indicates that these drugs may reduce eccrine sweat gland and sympathetic activity affecting these sweat glands. Further studies are needed on whether a decrease in sympathetic activity will have a positive effect on diabetes. Elektrodermal aktivite (EDA), sempatik sinir sistemi ile innerve olan ekrin ter bezlerinin aktivitesini yansıtan derinin elektriksel iletkenliğinin ölçümüdür. Çalışmamızda, metformin, vildagliptin ve metformin+vildagliptin kombinasyonu uygulanan diyabetik sıçanlarda elektrodermal aktivitenin, dolayısıyla sempatik aktivitedeki değişikliklerin değerlendirilmesi amaçlandı. Çalışmada 50 adet erkek Wistar sıçan kullanıldı. Sıçanlar 10’u kontrol, 40’ı deney grubu olacak şekilde ayrıldı. Deney grubundaki 40 hayvanda 45 mg/kg ip streptozotosin (STZ) uygulamasından sonra kan glikoz düzeyi 250 mg/dl’ yi geçen hayvanlar diyabetli olarak kabul edildi. Sıçanlara 15 gün boyunca gavaj ile çeşme suyu, 500 mg/kg metformin, 50 mg/kg vildagliptin, ve 500 mg/kg metformin+50 mg/kg vildagliptin verilerek diyabetik kontrol (n=10) ve deney grupları (3 grup, n=10) oluşturuldu. 15 gün sonunda kan glikozluri tekrar ölçüldükten ve diyabetin devam ettiği görüldükten sonra Biopac MP35 cihazı kullanılarak, ses uyarısı verilmeden önce dinlenim durumundaki tonik, işitsel uyarıdan sonra gelişen cevap fazik deri iletkenlik seviyesi (DİS) olarak kaydedildi. Gruplar arasındaki farklılıklar one-way Anova testi ve Posthoc Tukey testi ile belirlendi. P<0.05 anlamlı olarak kabul edildi. Hem tonik hem de fazik DİS diyabetli gruplarda arttı (p<0.001) ki bu diyabetli gruplarda sempatik aktivitenin arttığını gösterebilir. Metformin ve vildagliptin verilen gruplarda kan şekeri diyabetli gruba göre daha düşüktü. Tonik DİS, metformin+vildagliptin grubunda diğer deney gruplarına göre, fazik DİS ise metformin grubunda diyabetik gruba göre azaldı (p<0.0001). Vildagliptin ile metformin+vildagliptin gruplarının pik sayısı da tonik kayıtta diyabetik gruba göre azaldı (sırasıyla p<0.0001 ve p<0.05). Çalışmamızda, metforminin, ve metformin vildagliptin kombinasyonlarının fazik DİS de azalma oluşturması, bu ilaçların ekrin ter bezi ve bu ter bezlerine etkiyen sempatik aktiviteyi azalttığını gösterebilir. Sempatik aktivitede azalmanın diyabette olumlu etki oluşturup oluşturmayacağı ile ilgili daha ileri çalışmalara ihtiyaç bulunmaktadırItem HNF1A gene p.I27L is associated with early-onset, maturity-onset diabetes of the young-like diabetes in Turkey(2019) Beysel, Selvihan; Eyerci, Nilnur; Pinarli, Ferda Alparslan; Kizilgul, Muhammed; Ozcelik, Ozgur; Caliskan, Mustafa; Cakal, Erman; 31109344BackgroundThe molecular basis of the Turkish population with suspected maturity-onset diabetes of the young (MODY) has not been identified. This is the first study to investigate the association between HNF1A-gene single-nucleotide polymorphisms (SNPs) and having early-onset, MODY-like diabetes mellitus in the Turkish population.MethodsAll diabetic patients (N=565) who presented to our clinic between 2012 and 2015 with a clinical suspicion of MODY were included in the study. Analysis of HNF1A, HNFB, HNF4A, GCK gene mutations was performed using real-time polymerase chain reaction sequencing. After genetic analysis, diabetics (n=46) with HNF1A, HNF1B, HNF4A, GCK gene mutations (diagnosed as MODY) and diabetics (n=30) with HNF1B, HNF4A, GCK gene SNPs were excluded. Patients with early-onset, MODY-like diabetes (n=486) and non-diabetic controls (n=263) were included. Genetic analyses for the HNF1A gene p.S487N (rs2464196), p.A98V (rs1800574) and p.I27L (rs1169288) SNPs were performed using Sanger-based DNA sequencing among the control group.Resultsp.S487N and p.A98V was similar between the diabetics and controls in dominant and recessive models with no association (each, p>0.05). p.I27L GT/TT carriers (GT/TT vs. GG, OR=1.68, 95% CI: [1. 21-2.13]; p=0.035) and p.I27L TT carriers had increased risk of having MODY-like diabetes (GT/GG vs. TT, OR=1.56, 95% CI: [1. 14-2.57]; p=0.048). Family inheritance of diabetes was significantly more common in patients with the p.I27L TT genotype. The p.I27L SNP was modestly associated with having diabetes after adjusting for body mass index and age (=1.45, 95% CI: [1. 2-4.2]; p=0.036).ConclusionsThe HNF1A gene p.I27L SNP was modestly associated with having early-onset, MODY-like diabetes in the Turkish population. HNF1A gene p.I27L SNP might contribute to age at diabetes diagnosis and family inheritance.