AMYLIN INCREASES BONE VOLUME BUT CANNOT AMELIORATE DIABETIC OSTEOPENIA

Amylin normally secreted in a regulated fashion by the pancreatic beta -cells in parallel with insulin and has been reported to have bone-con serving properties. Type I diabetes mellitus results in a low-turnover osteopenia in the presence of decreased amylin, which is in contrast to type II diabetes where less bone loss, in the presence of high amyl in levels, occurs. We investigated the effects of amylin on bone miner al metabolism in normal and diabetic (streptozotocin-induced) rats, in order to ascertain whether amylin would modify the streptozotocin-ind uced diabetic osteopenia. Ten-week-old male Sprague-Dawley rats were r andomized as follows: group A (n = 18) received normal saline; group B (n = 18) received amylin; group C, diabetic rats (n = 23), received n ormal saline; and group D, diabetic rats (n = 23), received amylin. Am ylin (100 pmol/100 g b.w.) was administered by a daily subcutaneous in jection. Double calcein-labeled tibiae were removed for histomorphomet ric analysis followed sacrifice on day 19. Results showed no differenc e in blood ionized calcium between groups. Blood glucose remained abov e 600 mg/dl in the diabetic animals and was not affected by the admini stration of amylin. Serum osteocalcin, insulin-like growth factor-1 (I GF-1), parathyroid hormone (PTH), and 1,25 dihydroxyvitamin D [1,25(OH )(2)D] were significantly lower in the diabetic rats compared with con trol group A by day 19. Amylin produced higher levels of serum osteoca lcin in group B on day 9 (P < 0.05) compared with controls but returne d to control values (group A) by day 19; no such change occurred in th e diabetic group. Amylin administration did not influence IGF-1, 1,25( OH)(2)D or PTH levels compared with the untreated animals. Analysis of the bone histomorphometry showed a low-turnover osteopenia in the dia betic animals. Amylin administration resulted in a significant increas e in bone volume in the normal rats, group B (P < 0.05), but was unabl e to significantly alter this parameter in the diabetic animals. In co nclusion, amylin has a beneficial effect on the bone metabolism of the rat in vivo by increasing bone volume. It is, however, unable to over come the osteopenia caused by streptozotocin-induced diabetes mellitus at the doses used in this study.