The Influence Of Different Insulin Delivery On Type 2 Diabetic Mice, Blood Glucose, Blood Lipids And Oxygen Free Radical Metabolism

Insulin is a promising drug which is the most efficacious while with the lowest cost. Subcutaneous which is the conventional route of insulin administration has many potential disadvantages in the treatment of diabetes. Complications are the key points which are always a disturbing problem for diabetics, but complications can not be avoided by this conventional route. Unstable blood sugar level, disorders of lipid and free radicals metabolism are major factors which are recognized as contributors to the complicating diseases of diabetes. Intraperitoneal insulin administration attracts much attention nowadays because it can mimic the physiological portal route of insulin delivery.Experiments were performed by using KK mice which are ideal animal models with type 2 diabetes because of the characteristics of obesity, hyperglycemia, hyperlipidemia and hyperinsulinemia, which very similar to diabetic clinical manifestation. This paper focused on determing the differences of glycemia control, lipid and free radicals metabolism by chronic exogenous insulin delivery either by the intraperitoneal or by the subcutaneous route. The results have vital clinical significance of avoiding and postponing occurrence, development of complications, also can provide a better route of administration for clinical treatment.The results of pharmacodynamics indicated the blood sugar level could be stably controlled within normal scope (5.1±0.2) mmol/L by intraperitoneal route when the insulin dose was in the range of 1.1-1.7 U/kg, and the dose-response curve showed an obvious plateau phase, the dose-response curve showed a linear relation with the blood sugar level in range of 2.1-9.2 mmol/L by subcutaneous injection.Under given condition that subcutaneous dose 20%more than intraperitoneal dose. Determination of blood lipid contents showed that TG, LDL-c and HDL-c were not recoverd to the normal scope by subcutaneous injection group, but TG, TC, LDL-c and HDL-c were recovered to the normal level by intraperitoneal injection. This result showed that compared with subcutaneous injection, intraperitoneal injection can be more efficacious to correct the disorder of lipid metabolism.Determination of free radicals ability showed that compared with subcutaneous injection, intraperitoneal injection can be more efficacious to enhance the anti-oxidant ability and decrease the free radical production of the kidney and serum. In the liver, GSH-PX activity was enhanced to higher level by intraperitoneal injection than by subcutaneous injection, but SOD activity was enhanced to higher level by subcutaneous injection.As stated previously, intraperitoneal injection of insulin can control blood sugar level more stably, cause less fluctantion and better improve blood lipid contents compared with subcutaneous injection. Two routes of administrations of insulin are all able to decrease the free radical production to normal level in blood and liver, kidney, heart. The ways of regulating the free radical metabolism by intraperitoneal and subcutaneous injections may be different.