Amylin (AMY) is a 37 amino acid peptide cosecreted with insulin (INS) by pa
ncreatic beta -cells and absent in type I diabetes, a condition frequently
associated with osteopenia. AMY binds to calcitonin receptors, lowers plasm
a calcium concentration, inhibits osteoclast activity, and stimulates osteo
blasts. In the present study, we examined the effects of AMY replacement on
bone loss in a streptozotocin (STZ)-induced rodent model type I diabetes.
Of 50 male Wistar rats studied, 40 were made diabetic with intraperitoneal
STZ (50 mg/kg; plasma glucose concentrations >11 mM within 5 days). Ten non
diabetic control (CONT) rats received citrate buffer without STZ. Diabetic
rats were divided into four groups in = 10/group) and injected subcutaneous
ly with rat AMY (45 mg/kg), INS (12 U/kg), both (same doses), or saline (ST
Z; diabetic controls) once per day. After 40 days of treatment and five 24-
h periods of urine collection for deoxypyridinoline (DPD), the animals were
killed, blood was sampled, and femurs were removed. The left femur was tes
ted for mechanical resistance (three-point bending). The right femur was te
sted for total, diaphyseal (cortical bone), and metaphyseal (trabecular bon
e) bone densities using dual-energy S-ray absorptiometry (DXA). Bone was as
hed to determine total bone mineral (calcium) content. None of the treatmen
ts had any significant effect on femoral length and diameter. Untreated dia
betic rats (STZ; 145 +/- 7N) had lower bone strength than did nondiabetic C
ONT (164 +/- 38; p < 0.0,5). Total bone mineral density (BMD; g/cm(2)) was
significantly lower in STZ (0.2523 <plus/minus> 0.0076) than in CONT (0.282
6 +/- 0.0055), as were metaphyseal and diaphyseal densities. Diabetic rats
treated with AMY, INS, or both had bone strengths and bone densities that w
ere indistinguishable from those in nondiabetic CONT. Changes in bone miner
al content paralleled those for total BMD (T-BRID). Plasma osteocalcin (OC)
concentration, a marker for osteoblastic activity, was markedly lower in u
ntreated diabetic rats (7.6 +/- 0.9 ng/ml); p < 0.05) than in nondiabetic C
ONT (29.8 <plus/minus> 1.7; p < 0.05) or than in AMY (20.1 <plus/minus> 0.
7; p < 0. 05). Urinary DPD excretion, a marker for bone resorption, was sim
ilar in untreated and AMY-treated diabetic rats (35.0 <plus/minus> 3.1 vs.
35.1 +/- 4.4 nmol/mmol creatinine), intermediate in rats treated with INS (
49.9 +/- 2.7), and normalized in diabetic rats treated with both agents (58
.8 +/- 8.9 vs. 63.2 +/- 4.5 in CONT). Thus, in our STZ rat model of diabeti
c osteopenia, addition of AMY improved bone indices apparently by both inhi
biting resorption and stimulating bone formation.