Age-related changes in hepatic and splenic insulin receptors and serum insulin and glucose levels in inbred mice

Abstract

Inbred mice of strains A J , DBA 1J , and SJL J were housed and aged in our animal colony, and parameters of carbohydrate metabolism were assessed at various ages. The patterns of age-related change were both organ- and strain-specific. Age-related changes in two of the strains were associated with relative carbohydrate intolerance. Common to all three strains was a biphasic pattern of change in hepatic insulin receptor number, with a decrease in early life and a return to earlier levels late in life. In both A J and DBA 1J mice, there was a sharp increase in serum insulin level (twofold to 9.7-fold) that corresponded to the decrease in hepatic insulin receptors and was associated with hyperglycemia; no significant change in serum insulin or glucose levels was seen in SJL J mice, despite a similar biphasic pattern in hepatic insulin receptor concentration. Age-related changes in splenic insulin receptors resembled changes in the liver in A J and SJL J mice, ie, there were synchronous biphasic age-related patterns. This was not the case in the spleens of DBA 1J mice, in which we did not observe age-related changes. There was no change in insulin receptor affinity with age, nor was there any difference in affinity between tissues or mouse strains. The pattern of change in hepatic insulin receptors and serum insulin levels was more complex than has been previously recognized. We do not know the mechanisms responsible for this complex pattern, but it must involve at least two discrete age-related events. Further experiments will be necessary to elucidate the mechanisms underlying the pattern. Future studies of age-related change in carbohydrate metabolism in inbred mice must include comparisons among multiple ages rather than comparisons between only two ages, ie, young and old mice, as has usually been done in the past. Only by following age-related changes throughout life can we determine the dynamics of age progression and reveal the complexity of changes in carbohydrate metabolism.