The role of growth hormone in substrate utilization.
Substrate fluxes in response to growth hormone administration depend on both the calorie as well as acid-base balance. Growth hormone's acidogenic action as a consequence of promoting fatty acid utilization yields protons required for driving hepatic glutamate efflux; effective uncoupling of nitrogenous precursors from ureagenesis and recycling as glutamate bound for the periphery appears dependent upon this mechanism. Subsequent peripheral retrieval of the salvaged glutamate requires insulin-like growth factor-1 (IGF-1) activated uptake and acid-base homoeostasis. In addition to this nitrogen sparing acidogenic effect, growth hormone is also basogenic in combination with IGF-1 and acting on the kidney as a target organ. Therefore acid-base and nitrogen homoeostasis are normally attuned to one another through the co-ordinated action of growth hormone/IGF-1 on substrate fluxes. However during starvation ketoacid production as the consequence of incomplete fatty acid oxidation and ketone excretion swamps the basogenic limb and full-blown metabolic acidosis prevails; under this condition growth hormone's effectiveness in sparing nitrogen for anabolic processes is curtailed as glutamate (emanating from the liver) and glutamine (derived from muscle proteolysis) are directed to the kidneys, supporting ammoniogenesis: nitrogen balance is now sacrificed for acid-base homoeostasis. Underlying this state is an intracellular acidosis that may contribute to insulin resistance and developing hyperglycaemia in response to growth hormone. In acute injury, an additional acid load contributed from muscle proteolysis and cytokines reinforces an intracellular acidosis that further blunts growth hormone responsiveness and suppresses coupled IGF-1 production. From this perspective growth hormone's acidogenic and basogenic actions should balance for an effective anabolic response during hypermetabolic catabolic illnesses.
Welbourne
T C
TC
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
Milford
L
L
Carter
P
P
D000818:Animals; D004435:Eating / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D008660:Metabolism / Q000502:physiology*; D013217:Starvation / Q000503:physiopathology; D014947:Wounds and Injuries / Q000503:physiopathology
D013006:Growth Hormone