Study Of The Damage Of Pancreas Islet Treated With Streptozotocin And The Relativity Of The Damage And Hyperglycemia

Objective:At present, in the study to develop the animal model of diabetic mellitus treated with streptozotocin (STZ), there are different reports about blood glucose and glucose tolerance lacking a long period of observation after once injection of low dose STZ. There are much more study of morphological observation on pancreas islet than that of morphometry of pancreas islet in the hyperglycemic animals. It is still unclear what degree the total volume of the pancreas islet is decreased, whether there is positive relativity of the total volume of the pancreas islet and the level of blood glucose and whether pancreas islet damaged can reverse in the hyperglycemic animals. Few people study the non-hyperglycemic animals. It is lacking in study what degree the pancreas islet is damaged, whether the glucose tolerance is impaired, whether hyperglycemia is induced afterwards and whether animal model of type 2 diabetic mellitus is developed in the non-hyperglycemic animals. Morphometry using stereological methods was performed to study the damage of pancreas islet treated with STZ in rats and explore the relativity of the damage of pancreas islet and hyperglycemia combined with measurement of serum insulin and blood glucose and the intraperitoneal glucose tolerance test (IPGTT) in order to provide much more theoretic base to study animal model of diabetic mellitus induced by STZ.Methods:1. Experimental 1: ninety-eight ordinary male SD rats, aged 10~12 weeks, were randomly divided into control group with twenty-five rats, low dose group with fourty-four rats and high dose group with twenty-nine rats. Experimental 2: fourty-six ordinary male SD rats, aged 12~14 weeks, were randomly divided into control group with ten rats and high dose group with thirty-six rats. Rats in the low dose group received intraperitoneal injection of 30 mg/kg STZ, rats in the high dose group received injection of 60 mg/kg STZ and rats in the control group received intraperitoneal injection of equal dose acidified saline used to make fluid of STZ.2. At 7,14,28,42,56and 84 day after injection, observation on body weight, fasting blood glucose and IPGTT were performed. At 7 day after injection in Experimental 1 and at 84 day after injection in Experimental 2, measurement of serum insulin was performed, the pancreata were removed after excision and hydroxyethyl methacrylate resin-embeded pancreas sections were obtained in the high dose group and the control group. Observe the histology of the pancreas islet by light microscopy. Measure the area and total volume of the the pancreas islet using stereological methods.Results:1. Low dose STZ did not induce hyperglycemia or abnormal IPGTT at each time point in all annimals after injection in experimental 1.2. At 7 day after injection of high dose STZ in experimental 2, nineteen annimals had hyperglycemia, i.e the fasting blood glucose≥10 mmol/L, ten annimals had no hyperglycemia. At 84 day, there were nine animals alive respectively in the hyperglycemic and non-hyperglycemic annimals. Annimals alive with hyperglycemia were under hyperglycemic conditions at each time point and didn't reverse. Among the annimals alive with no hyperglycemia, there were six annimals whose fasting blood glucose levels were normal all the time, but glucose tolerance was impaired, there were three annimals whose fasting blood glucose levels were normal at first and under hyperglycemic conditions after 42 day.3. Serum insulin levels in the nine annimals with hyperglycemia treated with high dose STZ were significant decreased 66% in experimental 1 and 92% in experimental 2 compared with control group. Serum insulin levels in the nine annimals with no hyperglycemia had difference. Among the six annimals whose fasting blood glucose levels were normal all the time, there were three annimals whose serum insulin levels approached normal levels, and there were three annimals whose serum insulin levels stood in levels between the hyperglycemic group and the control group. Serum insulin levels in remained three annimals whose fasting blood glucose levels were under hyperglycemic conditions afterwards approached levels of the hyperglycemic group.4. The pancreas islets were damaged severely in the annimals with hyperglycemia treated with high dose STZ. The pancreas islets became small and were in the shape of disorder. Reduction in the numbers of cells in the pancreas islet was present. In pancreas sections, average areas of islet outline were significant decreased 30% in experimental 1 and 56% in experimental 2, numbers of islet outline of unit of area in pancreas section were significant decreased 63% in experimental 1 and 69% in experimental 2 and the total volumes of pancreas islet were significant decreased 74% in experimental 1 and 89% in experimental 2 compared with the control group. The damage of pancreas islet in the annimals with no hyperglycemia treated with high dose STZ had difference. Most of pancreas islets looked like normal and the total volumes of pancreas islet approached normal levels or stood in levels between the hyperglycemic group and the control group in the six annimals whose fasting blood glucose levels were normal all the time. Most of pancreas islets were damaged and the total volumes of pancreas islet approached levels of the hyperglycemic group in the three annimals remained whose fasting blood glucose levels were under hyperglycemic conditions afterwards.Conclusion:1. Pancreas islet didn't reverse after being damaged severely by high dose STZ and the animals would be under hyperglycemic conditions for a long time. High dose STZ did not induce hyperglycemia in a short period i.e at 7 day after injection in few animals because of less severe damage of pancreas islet. Most of animals were under normal conditions, but had impaired glucose tolerance. Animals remained whose pancreas islets were damaged severely relatively had hyperglycemia at 42 day after injection.2. Low dose STZ did not induce hyperglycemia or abnormal IPGTT in all animals because of slight damage of pancreas islet. If we want to develop animal model of type 2 diabetic mellitus assisted by STZ, it is possible for non-hyperglycemic animals treated with high dose STZ to provide a particular advantage for developing animal model of type 2diabetic mellitus compared with those animals treated with low dose STZ .