The study aims to evaluate the effect of saxagliptin, a specific inhibitor of dipeptidyl peptidase-4 enzymes, on body weight gain, lipid profiles, and cell death through apoptosis in rats with insulin resistance (IR). Male adult Sprague-Dawley rats (n = 32) were divided into 4 groups: control (Ctrl), IR, saxagliptin control, and IR treated with saxagliptin(IR + S). Insulin resistance was induced by 10% fructose in the drinking water for 8 weeks. Saxagliptin (10 mg/kg/day) was administrated by oral gavage for 2 weeks. Biochemical parameters were measured spectrophotometrically. Peptides were determined by the streptavidin-biotin-peroxidase method. Although the amount of food and liquid consumed are inversely proportional, the calories received are almost equal between both Ctrl and IR groups, as well as IR and IR + S groups. Increased homeostasis model assessment for insulin resistance, HOMA-β, triglycerides, and very low-density lipoprotein in the IR group were comparatively decreased by saxagliptin administration. The area percentage of caspase-3 and apoptotic peptidase activating factor-1 immunopositive cells in the IR + S group decreased compared with the IR group. Similarly, the percentages of caspase-8 and -9 immunopositive cells in the IR group were higher than the IR + S group. It was observed that the percentage of poly (ADP-ribose) polymerase-1 immunopositive cells was increased in the IR + S group compared with the IR group. Thus, saxagliptin may prevent IR-induced apoptotic cell death and regulate impaired homeostasis model assessment for insulin resistance and serum lipid levels.

ÖzetAmaç:Tip 2 diyabet, insülin direnci ve hiperglisemi ile karakterize edilen diyabetin en yaygin çeşididir. Obez bireylerin sayisindaki artiş ile Tip 2 diyabetik bireylerin sayisindaki artişin ilişkili olduğu bilinmektedir. Çalişmamizda sitagliptinin tip 2 diyabetik siçan mide ve duodenum dokularindaki kolesistokinin (CCK) ve kannabinoid (CB) 1 reseptör peptid miktarlarindaki değişimine olan etkisinin incelenmesi amaçlanmiştir. Gereç ve yöntem: Wistar albino yeni doğan siçanlar dört gruba ayrildi. Grup I: Siçanlara fizyolojik su intraperitoneal (i.p.) olarak verildi. Grup II: Beşinci günden itibaren fizyolojik suda çözündürülen 1.5 mg/kg sitagliptin subkutanöz (s.c.) olarak yeni doğan siçanlara 15 gün süreyle verildi. Grup III: Doğumdan sonra ikinci günde 100 mg/kg STZ yeni doğan diyabetik siçanlara i.p. tek doz verildi (Diyabet). Grup IV: Diyabetik siçanlara 15 gün süreyle sitagliptin verildi (Diyabet+Sitagliptin). Kesitler CCK ve CB 1 reseptör antikorlari kullanilarak streptavidin-biotin-peroksidaz yöntemine göre boyandilar. Bulgular: Diyabet+Sitagliptin grubu ile diyabet grubu karşilaştirildiğinda sitagliptin uygulanan diyabetik siçanlarin vücut ağirliklarinda bir düşüş saptandi. Diyabetiklerde, mide CCK immünpozitif hücre sayisi kontrole göre çok az azalirken, duodenumda artiş gözlendi. Kontrol ve diyabetik gruplar arasinda CB1 reseptör immünpozitif hücre sayisi mide ve duodenumda herhangi bir değişiklik göstermedi. Diyabet+Sitagliptin grubunun duodenumunda CCK ve CB 1 reseptör immünopozitif hücre sayisi diyabet grubu ile karşilaştirildiğinda anlamli bir azalma saptandi. Sonuç: Bulgularimiza göre, sitagliptin obezite kaynakli tip 2 diyabet tedavisinde kilo aliniminda düzenleyici olarak kullanilabilir. Pam Tıp Derg 2017;(1):15-22Anahtar sözcükler: Sitagliptin, mide, duodenum, Tip 2 diyabet, kolesistokinin, kannabinoid 1 reseptör, immünohistokimya. AbstractPurpose: Type 2 diabetes is the most common form of diabetes and characterized by insulin resistance and hyperglycemia. It is known that the increase in number of obese individuals is related with the increase in number of Type 2 diabetics. In our study, it was aimed to investigate the effect of sitagliptin on the changes of cholecystokinin (CCK) and cannabinoid (CB) 1 receptor peptides in newborn STZ-diabetic rat stomach and duodenum. Materials and methods: Wistar albino newborn rats divided into four groups. Group I: The saline was administered intraperitoneally (i.p) to rats. Group II: Newborn rat group, from the day five sitagliptin that dissolved in the saline was injected 1.5 mg/kg subcutaneous (s.c) for 15 days. Group III: Second day after the birth 100 mg/kg streptozotocin was administered i.p a single dose to the newborn diabetic rats (Diabetes). Group IV: Sitagliptin was given to diabetic rats for 15 days (Diabetes+Sitagliptin). Sections were stained with CCK and CB-1 receptor antibodies by streptavidin-biotin peroxidase technique. Results:The body weight was decreased in diabetic rats treated with sitagliptin when compared to diabetic rats. The ...