Kissler H J, Hofmann G, Gepp H, Erben R G, Schwille P O
Department of Surgery, Friedrich Alexander University, Erlangen, Germany.
Scand J Clin Lab Invest. 2000 May;60(3):175-87. doi: 10.1080/003655100750044820.
Primary disturbances in mineral metabolism and deficiencies in insulin and insulin-like growth factor-I (IGF-I) have been implicated in the pathogenesis of diabetic osteopenia. This prompted us to investigate whether normal bone minerals and bone morphology are preserved after pancreas transplantation. To this end, 8 inbred rats (transplants) were compared with 9 sham-operated rats (controls) 20 months after orthotopic pancreas transplantation. While basal levels of insulin remained unaffected by transplantation, an oral glucose load elicited hyperinsulinemia (integrated incremental response: mean +/- SEM, 62+/-8 nmol l(-1) 60 min in transplants vs. 32+/-6 nmol l(-1) 60 min in controls; p<0.01) in the presence of normal glucose levels. Fecal and urinary excretion and fractional intestinal absorption of calcium, magnesium and phosphorus, net calcium absorption and the respective serum mineral levels were unchanged after transplantation, as were those of the calciotropic hormones. Serum osteocalcin and bone alkaline phosphatase remained unaffected, and urinary excretion of pyridinium and deoxypyridinium were unchanged. Fasting plasma IGF-I concentration was significantly decreased in transplants (930+/-42 ng ml(-1)) vs. control rats (1074+/-49 ng ml(-1); p < 0.05). Despite similar physical and chemical properties of bone in both groups, histomorphometry revealed slight osteopenia in transplant rats, as reflected by a 38% reduction in the cancellous bone area of the proximal tibial metaphysis. Plasma IGF-I levels were significantly correlated with bone mineral apposition rate (r=0.70, p<0.02), osteoblast perimeter (r=0.60, p<0.05) and osteoid perimeter (r=0.60, p<0.05). In conclusion, pancreas transplantation preserves physical and chemical properties of bone, but bone metabolism is not completely normal after transplantation, as evidenced by decreased cancellous bone. This might have resulted from the insulin resistance associated with the lowering of the plasma IGF-I level, which was correlated with the mineral apposition rate.
矿物质代谢的原发性紊乱以及胰岛素和胰岛素样生长因子-I（IGF-I）的缺乏与糖尿病性骨质减少的发病机制有关。这促使我们研究胰腺移植后正常的骨矿物质和骨形态是否得以保留。为此，在原位胰腺移植20个月后，将8只近交系大鼠（移植组）与9只假手术大鼠（对照组）进行比较。虽然移植未影响胰岛素的基础水平，但在血糖水平正常的情况下，口服葡萄糖负荷会引发高胰岛素血症（综合增量反应：移植组平均±标准误为62±8 nmol l⁻¹ 60分钟，对照组为32±6 nmol l⁻¹ 60分钟；p<0.01）。移植后，钙、镁和磷的粪便及尿液排泄、肠道吸收分数、净钙吸收以及各自的血清矿物质水平均未改变，钙调节激素的水平也是如此。血清骨钙素和骨碱性磷酸酶未受影响，吡啶鎓和脱氧吡啶鎓的尿排泄也未改变。移植组空腹血浆IGF-I浓度显著低于对照大鼠（930±42 ng ml⁻¹ vs. 1074±49 ng ml⁻¹；p<0.05）。尽管两组骨骼的物理和化学性质相似，但组织形态计量学显示移植大鼠存在轻度骨质减少，这表现为胫骨近端干骺端松质骨面积减少38%。血浆IGF-I水平与骨矿物质沉积率（r=0.70，p<0.02）、成骨细胞周长（r=0.60，p<0.05）和类骨质周长（r=0.60，p<0.05）显著相关。总之，胰腺移植保留了骨骼的物理和化学性质，但移植后骨代谢并不完全正常，松质骨减少就是证据。这可能是由于与血浆IGF-I水平降低相关的胰岛素抵抗所致，而血浆IGF-I水平与矿物质沉积率相关。
