Abstract

It is now apparent that the shuttling of lactate through the interstitium and vasculature provides a major means of distributing carbohydrate potential energy during exercise. To further explore aspects of the 'lactate shuttle' hypothesis, two aims are identified. Under the umbrella of Aim 1, we will address a set of interrelated goals, all directed to understanding regulation of substrate supply during exercise.
Under Aim 1 a, we will evaluate the hypothesis that endurance training enhances lactate clearance during exercise.
Under Aim 1 b, we will address the hypothesis that sympatho-adrenal responses, specifically epinephrine, act to stimulate glycogenolysis in 'active' (contracting) muscles as well as 'inactive' (non-contracting) muscles and, thereby, provide for feed- forward regulation of lactate supply during exercise.
Under Aim 1 c, we will develop and test a model of lactate uptake and release during exercise. To explore aspects of substrate utilization during exercise, we will use combinations of tracer and non-tracer lactate infusion (ie., the 'lactate clamp'), gluconeogenic blockade (with 3-MPA), beta2-adrenergic blockade (with ICI 118,551), glucose clamping (with and without somatostatin), and epinephrine infusion. Additionally, tail suspension of rats during treadmill running to produce active (fore limb) and inactive (hind limb) muscle beds will be used to verify that endocrine signals are responsible for mobilization of glycogen and lactate release from inactive muscle beds during contraction in other muscle beds. By these means we hope to elucidate the hormonal and substrate signals coordinating the 'shuttle' mechanism.
Under Aim 2 we will address the hypothesis that a muscle cell membrane lactate transport protein (permease) exists and that presence of such a permease facilitates function of the 'lactate shuttle.' Specifically, we propose to isolate and purify the sarcolemmal lactate transport protein, as well as describe the regulation of protein induction in different muscle fiber types, and in response to exercise training.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK019577-12A2
Application #
2137351
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1990-04-01
Project End
1999-01-31
Budget Start
1995-02-01
Budget End
1996-01-31
Support Year
12
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Type
Other Domestic Higher Education
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

McClelland, Grant B; Khanna, Savita; Gonzalez, Gilda F et al. (2003) Peroxisomal membrane monocarboxylate transporters: evidence for a redox shuttle system? Biochem Biophys Res Commun 304:130-5
Brooks, G A (2002) Lactate shuttles in nature. Biochem Soc Trans 30:258-64
McClelland, Grant B; Brooks, George A (2002) Changes in MCT 1, MCT 4, and LDH expression are tissue specific in rats after long-term hypobaric hypoxia. J Appl Physiol 92:1573-84
Trimmer, J K; Casazza, G A; Horning, M A et al. (2001) Autoregulation of glucose production in men with a glycerol load during rest and exercise. Am J Physiol Endocrinol Metab 280:E657-68
Trimmer, J K; Casazza, G A; Horning, M A et al. (2001) Recovery of (13)CO2 during rest and exercise after [1-(13)C]acetate, [2-(13)C]acetate, and NaH(13)CO3 infusions. Am J Physiol Endocrinol Metab 281:E683-92
Bergman, B C; Horning, M A; Casazza, G A et al. (2000) Endurance training increases gluconeogenesis during rest and exercise in men. Am J Physiol Endocrinol Metab 278:E244-51
Brooks, G A (2000) Intra- and extra-cellular lactate shuttles. Med Sci Sports Exerc 32:790-9
Dubouchaud, H; Butterfield, G E; Wolfel, E E et al. (2000) Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle. Am J Physiol Endocrinol Metab 278:E571-9
Liu, J; Yeo, H C; Overvik-Douki, E et al. (2000) Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants. J Appl Physiol 89:21-8
Brooks, G A; Dubouchaud, H; Brown, M et al. (1999) Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle. Proc Natl Acad Sci U S A 96:1129-34

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