Insulin release, peripheral insulin resistance and muscle function in protein malnutrition: a role of tricarboxylic acid cycle anaplerosis.
Pancreatic beta-cells and skeletal muscle act in a synergic way in the control of systemic glucose homeostasis. Several pyruvate-dependent and -independent shuttles enhance tricarboxylic acid cycle intermediate (TACI) anaplerosis and increase beta-cell ATP:ADP ratio, triggering insulin exocytotic mechanisms. In addition, mitochondrial TACI cataplerosis gives rise to the so-called metabolic coupling factors, which are also related to insulin release. Peripheral insulin resistance seems to be related to skeletal muscle fatty acid (FA) accumulation and oxidation imbalance. In this sense, exercise has been shown to enhance skeletal muscle TACI anaplerosis, increasing FA oxidation and by this manner restores insulin sensitivity. Protein malnutrition reduces beta-cell insulin synthesis, release and peripheral sensitivity. Despite little available data concerning mitochondrial metabolism under protein malnutrition, evidence points towards reduced beta-cell and skeletal muscle mitochondrial capacity. The observed decrease in insulin synthesis and release may reflect reduced anaplerotic and cataplerotic capacity. Furthermore, insulin release is tightly coupled to ATP:ADP rise which in turn is related to TACI anaplerosis. The effect of protein malnutrition upon peripheral insulin resistance is time-dependent and directly related to FA oxidation capacity. In contrast to beta-cells, TACI anaplerosis and cataplerosis pathways in skeletal muscle seem to control FA oxidation and regulate insulin resistance.
Zoppi
Claudio C
CC
Department of Anatomy, State University of Campinas, Campinas, SP, Brazil. claudiozoppi@hotmail.com
Silveira
Leonardo R
LR
Oliveira
Camila A M
CA
Boschero
Antonio C
AC
Curi
Rui
R
Carneiro
Everardo M
EM
D004044:Dietary Proteins; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D044342:Malnutrition / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000378:metabolism*
D004044:Dietary Proteins; D007328:Insulin