Date of Award

1989

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

The purpose of this study was to examine the role of diabetes-associated hypothyroidism in changes in plantaris muscle contractile, histochemical and biochemical properties. Three experiments were designed to examine this relationship. Experiment I evaluated the time course of diabetes-associated hypothyroidism and examined the effect of daily triiodothyronine (T3) supplementation on serum T3 and thyroxine (T4) levels in the diabetic rat. The effects of diabetes and diabetes in conjunction with T3 supplementation on plantaris muscle contractile, histochemical and biochemical properties were examined in Experiments II and III respectively.;The results of Experiment I indicated that T3 levels exhibited a transient change after diabetes inducement, decreasing within the first week of the diabetic state and returning to normal by week three. In contrast, T4 levels were not significantly affected by the diabetic state until after the second week and remained in a reduced state through fifteen weeks of chronic streptozotocin (STZ)-induced diabetes. Daily supplementation of either 30, 50 or 75 ug/kg body weight of T3 to diabetic animals instigated a normal negative feedback response despite the diabetic state. These data would support the hypothesis that the alterations in thyroid hormone production observed in the diabetic state are a function of either an altered peripheral tissue responsiveness to thyroid hormone levels or a decrease in T4-5{dollar}\sp\prime{dollar}-deiodinase activity.;The effect of diabetes on plantaris muscle functional properties observed in this study was opposite to what would be expected in a hypothyroid state. Muscle temporal parameters were found to be significantly faster while absolute force generating ability was decreased and specific force generating ability was unaltered. These findings would suggest that factors other than thyroid hormone levels are responsible for the decrease in temporal parameters and absolute force generating ability of the plantaris muscle associated with the diabetic state. No consistent differences were observed in histochemical or biochemical properties of skeletal muscle from diabetic rats.;Contractile properties of the plantaris muscle in diabetic rats were not further affected by daily administration of T3. The lack of significant augmentations in temporal and force generating parameters suggests that skeletal muscle exposed to a diabetic-thyrotoxic state is not as affected by changes in serum T3 levels as would be skeletal muscle of a non-insulin deficient animal. Blood serum, histochemical and biochemical data confirmed the presence of a hyperthyroid state despite normal muscle functional parameters.;These data suggest that full expression of thyroid hormone levels is altered in the diabetic state. An interactive effect between insulin and thyroid hormone is postulated. The decline in insulin assoicated with the diabetic state may prevent full expression of thyroid hormone effects. Changes observed in skeletal muscle contractile, histochemical and biochemical properties with diabetes are not a result of diabetes-associated hypothyroidism.

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