Effects of metformin on serum and pancreas osteocalcin in type 2 diabetic rats

Abstract

Objective To investigate the effect of osteocalcin on function of β-cell in type 2 diabetic rats, and to analyze the relationship of metformin with osteocalcin, glucose, lipid and insulin metabolism. Methods Thirty-six healthy Sprague-Dawlay (SD) rats aged 8 weeks were randomly assigned to group A (n=12), B (n=12), and C (n=12). Those of group A were fed normally, while those of group B and C were fed with high-fat diet. At 8 weeks, 25 μg/g streptozotocin (STZ) was injected into abdominal cavity of rats in group B and C, and 25 μg/g sodium citrate solution was injected into rats in group A. At 10 weeks, oral glucose tolerance test (OGTT) was conducted, and the rats of group C were treated with 25 mg·kg-1·d-1 metformin for 4 weeks. At 4, 8, 10 and 14 weeks, serum levels of osteocalcin, fasting plasma glucose (FPG), fasting insulin (FINS), insulin sensitivity index (ISI), triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were tested. At 14 week, all the rats were killed, and the pancreatic tissue was observed under microscope. The expression of osteocalcin was detected by immunohistochemical method. One-way of variance, LSD t test and Pearson linear correlation were used for data analysis. Results At 10 weeks, 19 diabetic rats were successfully established in group B and C. At 8 weeks, body weight, TG, TC, and FINS in group B and C were significantly higher than those in group A (F values were 86.04, 74.25, 13.12 and 157.65, respectively; all P<0.01), while HDL-C and ISI were lower (F values were 12.13 and 24.01, respectively; all P<0.01). At 14 weeks, in group B and C, osteocalcin in pancreas were significantly decreased (0.84±0.09, 2.55±0.24 and 3.17±0.08, respectively; F value was 12.14, P<0.05). Pearson linear correlation analysis showed that pancreas osteocalcin was negatively correlated with FPG, TG and TC (r values were -0.811, -0.699 and -0.733, respectively; all P<0.05), and positively correlated with serum FINS, ISI, and HDL-C (r values were 0.826, 0.414 and 0.706, respectively; all P<0.05). Conclusions Osteocalcin could promote islet β-cells insulin secretion in type 2 diabetes rats. Serum and pancreas osteocalcin in group C was higher than that in group B after intervention with metformin, which suggests that metformin may promote the secretion of osteocalcin. Key words: Diabetes mellitus, type 2; Osteocalcin; Metformin