Abstract
In evolution, genes survived that could code for metabolic pathways, promoting long term survival during famines or fasting when suffering from trauma, disease or during physiological growth. This requires utilization of substrates, already present in some form in the body. Carbohydrate stores are limited and to survive long, their utilization is restricted to survival pathways, by inhibiting glucose oxidation and glycogen synthesis. This leads to insulin resistance and spares muscle protein, because being the main supplier of carbon for new glucose production. In these survival pathways, part of the glucose is degraded in glycolysis in peripheral (muscle) tissues to pyruvate and lactate (Warburg effect), which are partly reutilized for glucose formation in liver and kidney, completing the Cori-cycle. Another part of the glucose taken up by muscle contributes, together with muscle derived amino acids, to the production of substrates consisting of a complete amino acid mix but extra non-essential amino acids like glutamine, alanine, glycine and proline. These support cell proliferation, matrix deposition and redox regulation in tissues, specifically active in host response and during growth. In these tissues, also glucose is taken up delivering glycolytic intermediates, that branch off and act as building blocks and produce reducing equivalents. Lactate is also produced and released in the circulation, adding to the lactate released by muscle in the Cori-cycle and completing secondary glucose cycles. Increased fluxes through these cycles lead to modest hyperglycemia and hyperlactatemia in states of healthy growth and disease and are often misinterpreted as induced by hypoxia.
Highlights
Besides pain, fever and swelling, the responses to trauma, infection and other stresses include insulin resistance and often hyperglycaemia
We are inclined to consider this metabolic response as an undesirable effect because long-standing insulin resistance in type 2 diabetes mellitus is associated with
The metabolic switch, that leads to insulin resistance in inflammatory states consists on the one hand of inhibition of glucose oxidation and glycogen synthesis, and on the other hand off stimulation of gluconeogenesis from lactate and carbon skeletons of glucogenic amino acids derived from protein breakdown
Summary
Fever and swelling, the responses to trauma, infection and other stresses include insulin resistance and often hyperglycaemia. Almost 30 years ago, these findings were confirmed in more detail in a multi-catheterized pig model after operative trauma, and later after endotoxin infusion [29,30] In both studies, interplay between peripheral tissues and liver led to the production of glucose and glutamic acid in the liver, and muscle release of glutamine, alanine and glycine in markedly higher amounts than present in muscle protein and all other amino acids in modest amounts (Fig. 4). Intestine, tumorous tissue, brain and tissues that support foetal growth and very likely of other proliferating areas, adds to the lactate that is produced in the primary Cori-cycle in peripheral tissues and serves largely as substrate for renewed gluconeogenesis in liver and kidney
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call