Amylin increases bone volume but cannot ameliorate diabetic osteopenia.
Amylin is normally secreted in a regulated fashion by the pancreatic beta-cells in parallel with insulin and has been reported to have bone-conserving 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 amylin levels, occurs. We investigated the effects of amylin on bone mineral metabolism in normal and diabetic (streptozotocin-induced) rats, in order to ascertain whether amylin would modify the streptozotocin-induced diabetic osteopenia. Ten-week-old male Sprague-Dawley rats were randomized as follows: group A (n = 18) received normal saline; group B (n = 18) received amylin; group C, diabetic rats (n = 23), received normal saline; and group D, diabetic rats (n = 23), received amylin. Amylin (100 pmol/100 g b.w.) was administered by a daily subcutaneous injection. Double calcein-labeled tibiae were removed for histomorphometric analysis followed sacrifice on day 19. Results showed no difference in blood ionized calcium between groups. Blood glucose remained above 600 mg/dl in the diabetic animals and was not affected by the administration of amylin. Serum osteocalcin, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), and 1,25 dihydroxyvitamin D [1,25(OH)2D] were significantly lower in the diabetic rats compared with control group A by day 19. Amylin produced higher levels of serum osteocalcin in group B on day 9 (P < 0.05) compared with controls but returned to control values (group A) by day 19; no such change occurred in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)
Romero
D F
DF
Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141, USA.
Bryer
H P
HP
Rucinski
B
B
Isserow
J A
JA
Buchinsky
F J
FJ
Cvetkovic
M
M
Liu
C C
CC
Epstein
S
S
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D058228:Islet Amyloid Polypeptide; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D000682:Amyloid; D001786:Blood Glucose; D058228:Islet Amyloid Polypeptide; D010281:Parathyroid Hormone; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D002117:Calcitriol; D002118:Calcium