2.1 The Insulin Stress Response Theory-

The insulin stress response theory postulates two novel endocrine stress pathways that regulate the secretion of the hormone insulin following life threatening tissue injury. The preliminary research presented in the next section indicates that fasting serum insulin concentrations display a highly regulated response  to life threatening injury. This highly regulated response over time following life threatening injury is postulated to result from a specific secretory endocrine response by the pancreas to the physical stress of tissue injury. 

This theory postulates that the changes in fasting serum insulin concentration result from a specific endocrine stress response which regulates a change in glucose stimulated insulin secretion (GSIS) by the beta cells of the pancreas in response to injury. The changes in fasting serum insulin concentrations following life threatening injury are highly correlated with serum concentrations of endocrine mediators that are known to mediate changes in GSIS. These features indicate that insulin secretion by pancreas following life threatening injury is regulated by two endocrine stress pathways that are activated in response to the physical stress associated with tissue injury. 

The preliminary research indicates that changes in fasting serum insulin concentration over time following life threatening injury display characteristic features of a stress response to injury. The insulin stress response theory proposes that these changes in fasting insulin concentration over time represent a temporary and reversible change in GSIS by the pancreas in response to injury. When the changes in fasting serum insulin concentration are plotted graphically over time following injury a characteristic pattern is observed which has features similar to other stress hormones secreted following injury.

This insulin stress response to life threatening injury varies between individuals depending on factors related to the underlying mechanisms of these two endocrine pathways that mediate characteristic changes in GSIS and fasting insulin concentrations. Importantly, due to these underlying mechanisms, the insulin stress response to injury is best demonstrated when fasting serum insulin concentrations are analysed by comparing the change from pre-injury (unstressed) to the immediate post-injury (stressed) state- the delta value ΔV. When this change is measured from the unstressed to the stressed state, the highly regulated nature of the insulin secretory response to tissue injury can be most accurately demonstrated. 

This comparison involves measuring fasting serum insulin concentrations in both the unstressed and the stressed states. The unstressed state is defined as resting metabolic conditions where there is the absence of any physical  stress or noxious stimuli that produce tissue injury. The stressed state is defined as the endocrine and metabolic conditions that are activated following any life threatening host tissue injury. This involves tissue injury sufficient to produce a stress response.  Typically this includes tissue injurres secondary to trauma, haemorrhage, burns, exposure to toxins. hypo- and hyperthermia or tissue ischaemia/reperfusion injury due to impaired blood supply.