The potential osteogenic effects of systemic leptin and insulin administration in streptozotocin-induced diabetic female rats

OBJECTIVE: To evaluate the effect of leptin administration on some biochemical parameters of bone turnover in diabetic rats using either leptin alone or a combination of leptin and insulin.

METHODS: The study was carried out on 32 female Wistar rats supplied by the Medical College animal house at King Khalid Hospital, Riyadh, Kingdom of Saudi Arabia during the period from March to December 2006. Rats were divided into 4 groups (8 rats each), controls, non-treated diabetic, leptin-treated diabetic, and leptin plus insulin-treated diabetic rats. After induction of diabetes by 6 weeks, treatment with leptin either alone or combined with insulin was continued for 2 weeks more. At the end of treatment, serum samples were taken to measure levels of bone alkaline phosphatase (BAP), alkaline phosphatase, osteocalcin, insulin like growth factor-1 (IGF-1), parathyroid hormone (PTH), glucose, creatinine, calcium ions (Ca2+), and phosphorus using enzyme-linked immunoassay (ELISA) and spectrophotometric methods. Body weight and urinary calcium excretion were also measured.

RESULTS: Combined leptin and insulin treatment produced a significant increase of serum BAP and a decrease of urinary calcium and serum glucose as compared to rats treated by leptin only, and a significant increase of BAP, alkaline phosphates, IGF-1, and glucose and a decrease in osteocalcin as compared to control rats. Positive correlations were detected between serum IGF-1 levels and each of BAP, alkaline phosphatase, and osteocalcin in diabetic rats treated by leptin, and those with leptin plus insulin.

CONCLUSION: Combined leptin plus insulin treatment can offer extra gain of bone formation over leptin treatment alone. Confirmation of these preliminary observations must await careful long-term studies of bone turnover in experimental diabetes.