High insulin and low IGF-I plasma levels following pancreas transplantation in rats. Implications for bone and mineral metabolism

Primary disturbances in mineral metabolism and deficiencies in insulin and insulin-like growth factor-I (IGF-I) have been implicated in the pathogenes is of diabetic osteopenia. This prompted us to investigate whether normal b one minerals and bone morphology are preserved after pancreas transplantati on. To this end, 8 inbred rats (transplants) were compared with 9 sham-oper ated rats (controls) 20 months after orthotopic pancreas transplantation. W hile basal levels of insulin remained unaffected by transplantation, an ora l 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 calciu m, magnesium and phosphorus, net calcium absorption and the respective seru m mineral levels were unchanged after transplantation, as were those of the calciotropic hormones. Serum osteocalcin and bone alkaline phosphatase rem ained unaffected, and urinary excretion of pyridinium and deoxypyridinium w ere unchanged. Fasting plasma IGF-I concentration was significantly decreas ed in transplants (930 +/- 42 ng ml(-1)) vs. control rats (1074 +/- 49 ng m l(-1); p < 0.05). Despite similar physical and chemical properties of bone in both groups, histomorphometry revealed slight osteopenia in transplant r ats, as reflected by a 38% reduction in the cancellous bone area of the pro ximal tibial metaphysis. Plasma IGF-I levels were significantly correlated with bone mineral apposition rate (r = 0.70, p < 0.02), osteoblast perimete r (r = 0.60, p < 0.05) and osteoid perimeter (r = 0.60, p < 0.05). In concl usion, 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 lev el, which was correlated with the mineral apposition rate.