Effect of muscle fibre type on the relative contribution of muscle lactate glyconeogenesis to glycogen resynthesis following high intensity exercise

Bradley Kelly

    Research output: ThesisDoctoral Thesis

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    Abstract

    Muscle glycogen plays an important role in supporting the energy demands associated with high intensity physical activity. Since a large proportion of this fuel is mobilised in response to a single bout of intense exercise, it is important to rebuild rapidly these muscle glycogen stores post-exercise. Although this can be achieved with the ingestion of carbohydrates, most animal species have the capacity to replenish their muscle glycogen stores even without food. There is compelling evidence that this occurs at the expense of the lactate that accumulates in response to high intensity exercise.

    Two pathways can support the conversion of lactate into muscle glycogen, namely the Cori cycle and muscle lactate glyconeogenesis. The Cori cycle involves the release of lactate into the blood and its recycling to glucose via hepatic/renal gluconeogenesis before this glucose is stored as muscle glycogen. Muscle lactate glyconeogenesis, in contrast, operates exclusively in skeletal muscles rich in type II fibres and not in type I fibres, and involves the intramuscular conversion of lactate into muscle glycogen. It is still unclear whether the relative contribution of lactate glyconeogenesis differs between type IIa and IIb muscle fibres. Since, glucose transport capacity in rats is higher in the red (rich in type IIa fibres) compared to the white gastrocnemius muscles (rich in type IIb fibres), the primary purpose of this thesis was to test the hypothesis that the relative contribution of lactate glyconeogenesis in rats is higher in muscles rich in type IIb fibres.

    One indirect way to evaluate the contribution of the aforementioned pathways is to inject rats recovering from exercise with [U-14C]glucose to determine the rate of glycogen synthesis from glucose. The differences between the amount of glycogen deposited during recovery and that derived from [U-14C]glucose and the hexose glyconeogenesis. Using this experimental approach, this thesis shows that during recovery from high intensity exercise, lactate glyconeogenesis, glucose, and the HMP contribute 54.5, 30.4 and 15.1%, respectively, of the glycogen deposited in the white gastrocnemius muscles. In contrast, lactate glyconeogenesis is not involved in the red gastrocnemius muscles, with glucose and the HMP contributing 85.3% and 11.1%, of the glycogen being replenished. On the basis of these findings, it is concluded that the relative contribution of lactate glyconeogenesis to glycogen repletion in rats is higher in muscles rich in type IIb fibres than in those rich in type IIa fibres, with lactate glyconeogenesis playing no role in muscles rich in type IIa fibres.

    One limitation with the aforementioned findings is that they are based on an indirect rather than a direct estimate of lactate glyconeogenesis. For this reason, our next objective was to evaluate more directly the contribution of lactate glyconeogenesis to glycogen repletion by taking advantage of the observation that only carbons 1 and 6 of glycogen-glucosyl residues are labelled when [3-13C]lactate is converted intramuscularly to glycogen, whereas carbons 1, 2, 5 and 6 are labelled when hepatic gluconeogenesis is involved. Using this novel approach, we found that in the red and white gastrocnemius muscles, glucose is the primary carbon source for the replenishment of muscle glycogen stores, with the contribution of lactate glyconeogenesis being far less important, irrespective of muscle fibres type (<21%). Our most liberal estimates indicate that the contribution of glucose is 60% and 82% in the white and red gastrocnemius muscles, respectively, and that lactate glyconeogenesis is 21% and 8.1%. These findings are consistent with the Cori cycle playing a major role in recycling lactate into muscle glycogen post-exercise, but not lactate glyconeogenesis. Although our two experimental approaches yield similar findings with respect to the lesser role played by lactate glyconeogenesis in type IIa muscle fibres, they differ markedly with respect to the role attributed to lactate glyconeogenesis in type IIb muscle fibres. This mismatch may be explained if carbon sources other than lactate, HMP, and glucose are involved in the replenishment of muscle glycogen stores. In conclusion, this thesis shows for the first time that during recovery, lactate glyconeogenesis plays no role in the replenishment of glycogen in muscles rich in type IIa fibres, but its role in type IIb fibres is still unresolved.

    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2013

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