الفهرس 
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Abstract
Diabetes mellitus is a metabolic syndrome characterized by high blood glucose levels that result from defects in either insulin secretion, action, or both. Diabetes mellitus was classified into type I, type II, gestational and other types of diabetes mellitus.
Lipid abnormalities might play a role in the pathogenesis of the complications in diabetes. Oxidative stress describes a condition in which intracellular production of reactive oxygen species (ROS) challenges the capability of cellular antioxidant systems to neutralize them, consequently causing serious cellular damage and complications. Vascular dysfunction may play a major role in the pathogenesis of diabetic cardiovascular diseases.
Incretin hormones, including GIP and GLP-1, have received much attention because of their important role both in the physiology of glucose homeostasis and in the pathophysiology of type II diabetes. Dipeptidyl peptidase-4 (DPP-4) is a glycoprotein peptidase present in a soluble form and a membrane-bound form with an extracellular enzymatic domain and an intracellular domain involved with signal transduction cascades. It is responsible for the inactivation of a number of hormones and peptides; including the incretin hormones, substance P, and chemokines. Vildagliptin is a potent and selective inhibitor of DPP-4, which extends the physiological effects of GLP-1 and GIP.
The aim of the present study is to investigate and compare the effects of DPP-4 inhibitor (vildagliptin) on glycemic state, arterial blood pressure and vascular reactivity in type I and type II diabetes mellitus in rats.
Fifty male albino rats of local strain were used in this investigation. Rats were divided into the following three groups:
1. Non-diabetic group (10 rats).
2. Type I diabetic (Type I DM) groups (20 rats):
2-a) Type I DM non-treated group (10 rats).
2-b) Type I DM Vildagliptin-treated (Vil-treated) group (10 rats).
3. Type II diabetic (Type II DM) groups (20 rats):
3-a) Type II DM non-treated group (10 rats).
3-b) Type II DM Vildagliptin-treated (10 rats).
At the end of the experiment, retro-orbital fasting blood samples were taken for measurement of: 1- Serum glucose, HbA1c, serum insulin and plasma bioactive GLP-1levels; then HOMA-IR index was calculated. 2- Lipid profile: Serum cholesterol, serum TG, serum HDL –cholesterol and LDL-cholesterol was calculated. 3- Serum MDA and TAC.
After that, the rats were anesthetized and aortic cannulation was done for determination of arterial blood pressure (ABP) and examining vascular reactivity to different vasoactive agents, NE, Ang-II, ACh and SNP.
Results showed that serum glucose and blood HbA1c were significantly higher in type I and type II diabetic (both non-treated and Vil-treated) groups when compared to the corresponding values in non-diabetic group. The previous parameters were significantly lower in type II Vil-treated group when compared to the corresponding values in the non-treated group. On the other hand, they were insignificantly changed in type I Vil-treated group when
compared to the corresponding values in the non-treated group. In addition, they were significantly lower in type II vil-treated group when compared to the corresponding values in type I Vil-treated group.
Serum insulin, HDL-cholesterol and TAC were significantly lower in type I and type II diabetic (both non-treated and Vil-treated) groups when compared to the corresponding values in non-diabetic group. HDL-cholesterol and TAC were significantly higher in type I and type II Vil-treated groups when compared to the corresponding values in type I and type II diabetic non-treated groups respectively. Serum insulin level was significantly higher in type II Vil-treated group, but it showed insignificant change in type I Vil-treated group when compared to the corresponding values in the correlated non-treated groups. Serum insulin, HDL-cholesterol and serum TAC levels were significantly higher in type II Vil-treated group when compared to the corresponding values in type I Vil-treated group.
Serum cholesterol, TG, LDL-cholesterol and MDA levels were significantly higher in type I and type II diabetic (both non-treated and Vil-traeted) groups when compared to the corresponding values in non-diabetic group. All the previous parameters were significantly lower in type I and type II Vil-treated groups when compared to the corresponding values in the non-treated groups. Serum cholesterol, TG, LDL-cholesterol and MDA levels were significantly lower in type II Vil-treated group when compared to the corresponding values in type I Vil-treated group.
There was insignificant change in HOMA-IR index and plasma bioactive GLP-1 level in type I diabetic (both non-treated and Vil-
treated) groups when compared to the corresponding values in non-diabetic group. But HOMA-IR index was significantly higher while plasma bioactive GLP-1 level was significantly lower in type II diabetic non-treated group when compared to the corresponding values in the non-diabetic group. HOMA-IR index was insignificantly changed while plasma bioactive GLP-1 level was significantly higher in type I Vil-treated group when compared to the corresponding values in the non-treated one. On the other hand, HOMA-IR index was significantly lower while plasma bioactive GLP-1 level was significantly higher in type II Vil-treated group when compared to the corresponding values in the non-treated group.
Upon comparing type II and type I non-treated groups; serum glucose, HbA1c and plasma bioactive GLP-1 were significantly lower while serum insulin and HOMA-IR index were significantly higher in type II non-treated group when compared to the corresponding values in type I non-treated group. On the other hand, there was insignificant difference in (serum total cholesterol, TG, LDL-cholesterol, HDL-cholesterol, serum MDA and TAC) between the two diabetic non-treated groups.
Systolic, diastolic and mean arterial blood pressure levels of type I DM and type II DM both (non-treated and Vil-treated) groups were significantly higher when compared to the corresponding values of non-diabetic group. Systolic, diastolic and mean arterial blood pressure levels of type I and type II diabetic Vil-treated groups were significantly lower when compared to corresponding values of non-treated groups. Systolic, diastolic and mean arterial blood pressure levels of type II diabetic non-treated group were insignificantly different when compared to the corresponding values of type I
diabetic non-treated group. On the other hand, in type II diabetic Vil-treated group these parameters were significantly lower when compared to the corresponding values of type I diabetic Vil-treated group.
There was significantly attenuated vascular reactivity for vasoconstrictors (NE and Ang-II) and vasodilators (ACh and SNP), with the three doses used, in type I DM and type II DM both (non-treated and Vil-treated) groups when compared to corresponding values of non-diabetic group. Vascular reactivity for vasoconstrictors (NE and Ang-II) and vasodilators (ACh and SNP), with the three doses used, was significantly improved in both type I DM and type II DM Vil-treated groups when compared to the corresponding values in type I DM and type II DM non-treated groups respectively. Vascular reactivity for vasoconstrictors (NE and Ang-II) and vasodilators (ACh and SNP), with the three doses used, was significantly improved in in type II DM Vil-treated group when compared to the corresponding values in type I DM Vil-treated group.