Influence of anti-diabetic drugs on alveolar bone metabolism during tooth movement in experimental models of type 1 and 2 diabetic rats

Abstract

Bone complications caused by Diabetes melittus (DM) is one of the major disorders that affect the population. Antidiabetic drugs such as insulin and biguanides have been widely used for DM control. Both drugs act directly on bone remodeling process and their effects during tooth movement are not well defined. The purpose is to verify the effects of insulin and metformin on alveolar bone remodeling during orthodontic tooth movement in diabetic type 1 (DM1) and 2 (DM2) rats. One hundred eighty rats will be randomly divided into groups: Normoglycemic (NG, n=30) which will receive intraperitoneal (i.p.) injection of saline 0.9%, DM1 (n= 90) induced by i.p. 50mg/kg streptozotocin and DM2 (n = 60) induced by high-fat diet and i.p. 30mg/kg of streptozotocin. After 7 days, the animals of the untreated subgroups (ST): ST-NG (n= 30), ST-DM1 (n= 30) and ST-DM2 (n= 30), will receive saline solution daily. The animals of the Treated subgroups (T) with: Insulin (TINDM1, n= 30) will receive 6U insulin, Metformin (TMF-DM2, n=30) 150 mg/kg of metformin, and Insulin and Metformin (TIN+MFDM1, n=30) 150 mg/kg of metformin plus insulin dosage should be adjusted according to blood glucose level. 14 days after the induction, the first right upper molar will be mesializated with 50g of force and the contralateral molar will serve as control. In days 3, 7 and 14 after orthodontic appliance installation, the hemimaxillas/group will be analyzed by micro-CT and histomorphometry to determine the amount of tooth movement and quality of bone remodeling in pressure and tension sides. Immunohistochemistry analysis will be evaluated the expression of cytokines involved in the formation/activation and survival of osteoclasts (TNF-±, RANKL, OPG and HMGB1, RAGE) and in the differentiation and activity of osteoblasts (Runx-2, OC and ALP). Thus we aim to check if Metformin associated or no to insulin can have a beneficial effect on bone remodeling process. (AU)