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

Abstract

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.

FTIR Spectroscopic Investigation of Mineral Structure of Streptozotocin Induced Diabetic Rat Femur and Tibia

“…DM can affect bone formation and resorption by creating several metabolic irregularities in calcium-phosphate and acid-base balances. Primary disturbances in vitamin D and mineral metabolisms and a deficiency of insulin and IGF-I have been implicated in the pathogenesis of diabetic bone disease in animal models and IDDM patients [1,2,[17][18][19]. On the other hand, free radicals have been shown to be involved in osteoclastogenesis and in bone resorption [20] and it is thought that diabetes mellitus is associated with increased oxidative stress.…”

Effect of Selective Denervation of the Rat Pancreas on Pancreatic Endocrine Function

“…Two studies by Kissler et al [29,30], using orthotopic pancreas transplantation in rats, have shown that stimulated arterial insulin levels did not vary between controls and transplanted animals 3 months after operation while 20 months after transplantation oral glucose load elicited hyperinsulinemia. Berry et al [31] and Baumgartner et al [32] did not observe any differences in insulin levels after extrinsic pancreatic denervation and partial pancreatectomy in dogs.…”