Degree Name

Doctor of Philosophy (PhD)


Department of Biomedical Science - Faculty of Science


Insulin resistance (IR) is thought to be a major aetiological factor in the development in type II diabetes and the Metabolilc Syndrome, yet the underlying mechanisms behind IR remain unknown. Both resistance (RT) and aerobic (AT) exercise training lead to an increase in insulin sensitity (IS), however it is uncertain as to whether the effect of exercise on IS extends beyond the last exercise bout and which mode of exercise (RT or AT) is most beneficial. A human exercise intervention trial comparing the effect of RT and AT on insulin sensitivity measured 72 hours after the last exercise bout was used to examine the two previous questions. The oxidative capacity of the muscle and the membrane phospholipid fatty acid composition are considered possible mechanisms relating exercise and IR. Both of these were measured to see if the changes in IS parallel these proposed mechanistic markers. A previous animal study has shown that exercising rats have lower levels of unsaturated fatty acids in their membranes compared to sedentary rats, suggesting that exercise may have a negative effect on one of the possible mechanisms related to IS. This thesis set out to replicate this finding in animals and determine if the same relationship is seen in humans. Also diet composition was monitored in both rats and humans to determine if exercise induced changes in membrane phospholipid fatty acid composition have an effect on dietary intake. The first study performed was a human exercise intervention trial. 20 healthy sedentary males aged between 30 and 55 years were randomly allocated into either an AT group or RT group. Both groups exercised for 10 weeks, 3 times per week for 45 minutes each session. Total amount of work (kJ) performed during each training session was matched for both groups. Following training fasting insulin levels(In transformed) did change significantly (p(less than)0.05) in both groups (2.8 + 0.11 to 2.58 + 0.13, AT: 2.67 + 0.14 to 2.59 + 0.17, RT) with the reduction in the AT group appearing to be greater than the RT group. Peripheral IS, measured by hyperinsulinemic euglycemic glucose clamps, did not change significantly over the training period in either group (4.3 + 0.3 to 4.8 + 0.7, AT: 4.4 + 0.9 to 4.2 + 0.8, RT -1).min(superscript -1). Hepatic insulin resistance, indexed by HOMA-R, reduced significantly in both groups over the training period (1.3 + 0.1 to 1.1 + 0.1, AT: 1.3 + 0.2 to 1.2 + 0.2, RT). Citrate Synthase activity in skeletal muscle increased significantly in both groups over the training period (12.3 + 1.3 to 17.4 + 1.1, AT: 12.2 + 0.8 to 15.1 + 0.9, RT ?mol.min(superscript -1).g(superscript -1). Unsaturation index (UI) a measure of membrane fluidity, increased significantly in both groups (157.7 + 3.8 to 163.4 + 3.4, AT 142.6 + 10.4 to 150.5 + 8.9, RT). Both groups exhibited a significant decrease in poly-unsaturated fatty acid (PUFA) consumption (14.6 + 1.9 to 13.0 + 0.9, AT: 20.9 + 2.2 to 16.3 + 0.9, RT % of total fat intake) and a significant increase in saturated fatty acid (SFA) consumption (47.46 + 2.1 to 48.14 + 1.3, AT: 39.6 + 3.1 to 44.6 + 2.0, RT % of total fat intake). The 10 week exercise programs in humans had no effect on peripheral IS 72 hours after the last exercise bout, indicating that the effect of exercise on peripheral IS is an acute one. However there was a significant decrease in hepatic IR over the training period in both groups 72 hours after the last exercise bout. In addition the majority of this effect appeared to occur in the AT group. The therapeutic implication of this finding is that for maximum effect on insulin sensitivity individuals should exercise more frequently than every 72 hours and that their program should be based on AT. An anecdotal observation made by the author of this thesis was that the RT program was much better received than the AT program. There fore the inclusion of RT may improve compliance in an exercise training program. No strong relationship between changes in skeletal muscle citrate synthase and IS was found. A favourable change in the membrane phospholipid fatty acid composition of both groups, as indicated by an increase in the UI of both groups was not related to changes in IS. Thus the oxidative capacity of the muscle and the fluidity of the skeletal muscle membrane may not be central mechanisms in the relationship between IS and exercise. The animal exercise study saw 12 female Wistar rats randomly allocated into 2 groups, a sedentary control group (SED; n=6) and an exercise group (EX; n=6), performing voluntary wheel cage running. Rats in both groups had adlibitum access to 2 diets which were identical except for fat composition, with one diet high in saturated fat and the other high in unsaturated fat. The exercise period lasted for 34 days with an eight day baseline period. Upon conclusion all rats were fasted for 24 hours, killed and their red quadriceps extracted. The UI of the EX group (214 + 5.5 EX) was significantly lower than the SED group (232.2 + 3.5 SED). During baseline, diet preference between the two groups did not differ, however during the exercise period of the EX group consumed significantly more of the unsaturated fat diet (62.9 + 7.1 - 59.5 + 5.4, SED; 65.1 + 5.2 - 71.7 + 5.3, EX; % intake). Distance ran was shown to have an effect on dietary intake with the greater the distance ran the more unsaturated diet consumed (F(1,9) = 5.29, P = 0.024). Both the human and rat studies showed a significant change in dietary intake in response to the exercise training. The rat study showed that exercise lead to an increase in the consumption of unsaturated fatty acids. An intriguing possibility for this change in diet intake is that the rats, driven by some intrinsic drive were attempting to replenish their membranes. In humans the opposite occurred with a decrease in PUFA consumption and an increase in SFA consumption. This could suggest that no such intrinsic drive exists in humans. However instinctual dietary choices of the human subjects may have been altered by social and media influences promoting reduced total fat consumption. An unintended and potentially deleterious consequence of this may be a selective reduction in intake of the more visible PUFA component of dietary fat.

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