Effect of Anti diabetic Drugs on Glucose-6-phosphatase Activity in Patients with Type 2 Diabetes Mellitus

number: 
3683
English
department: 
Degree: 
Author: 
Zainab Salih Hallab
Supervisor: 
Dr. Alaa Hussain Jawad Asst. prof))
year: 
2016

Background:
       Type 2 Diabetes mellitus  is a disease characterized by chronically elevated blood glucose levels, even when fasting  largely due to increased endogenous glucose production. In liver, glucose-6-phosphatase catalyses the terminal step of glycogenolysis and gluconeogenesis. The classical role of glucose-6-phosphatase in the liver is the production of glucose for release into the blood. This correlation between type 2 diabetes and glucose-6-phosphatase makes this enzyme an appealing drug target for control of blood glucose levels as its inhibition would directly prevent the release of free glucose into the blood stream. Aims of  the study were to assess the effects of anti-diabetic drugs( metformin and  metformin  plus glibenclamide) on Glucose-6-phosphatase  activity, serum leptin concentration, Fasting plasma glucose (FPG) , Glycated  hemoglobin (HbA1c%) and lipid  profile   in type 2 diabetic patients and to study the factors that affect the  binding between Glucose-6-Phosphatase and     biotin antibody  in all diabetic patients and control. 

Subjects, Materials and Methods:
This study includes (84) subjects, their age ranged from (40 to 54) years. (20) subjects were healthy chosen as control group and (64) patients with type 2 diabetes mellitus were divided into three groups
according to their type of anti diabetic therapy  : (23) newly diagnosed group without therapy ( Group1) , (20) with  metformin therapy (Group2) and (21)  with  metformin plus  glibenclamide therapies( Group3) . In the first part of the study Glucose- 6 -Phosphatase   (G-6-Pase) activity  and Leptin hormone level were quantitatively determined in patients and healthy subjects by Enzyme-Linked Immuno sorbent Assay [ELISA] test.In addition to that, the duration of disease, duration of taking treatment,fasting plasma glucose (FPG), Glycated hemoglobin (HbA1c%), body mass index (BMI), and lipid profile were identified in the patients. In the second part we study the characteristics of the binding of biotin antibody with G-6-Pase in the sera of the  healthy subjects and patients. Different factors affecting this binding were studied such as concentration of antibody, concentration of antigen, temperature, and incubation time.

Results:
 This study showed the following:
Part I:
- The levels of G-6-Pase activity and serum leptin hormone are found to be significantly higher in diabetic patients compared with healthy control group (P<0.05).  
- The levels of  G-6-Pase activity and serum leptin hormone  were found to be  significantly higher in newly diagnosed group when compared with metformin group,metformin plus glibenclamide group and control group(P<0.05).
- A significant correlation  (P<0.05) was found between G6-Pase activity and  FPG   in all diabetics groups ( newly diagnosed group, metformin group, metformin plus glibenclamide group) and a significant correlation between G-6-Pase activity  and  HbA1c % in newly diagnosed group and metformin group.
-No significant correlation (P>0.05) was found between the level of leptin and G-6-Pase activity and significant correlation (P<0.05) was found between the level of leptin and BMI in all diabetic groups.