Insulin resistance is increasingly being seen as a causative agent in the development of Western lifestyle diseases. Poor diet may contribute significantly to the development of insulin resistance. In particular, low quality foods increase oxidative stress, both through the direct generation of free radicals and also indirectly through the oversupply of nutrients to the main energy producing pathways. Further, low quality diets also lack antioxidant phytonutrients that can quench free radical chain reactions and lower oxidative stress levels. Oxidative stress may interfere with the insulin signal cascade and thus induce insensitivity to the action of insulin. As well as diet, stress may also lead to the development of insulin resistance. The stress reaction causes the release of glucocorticoids which may in turn down regulate insulin sensitivity. Pathological conditions characterised by high levels of circulating glucocorticoids, such as Cushing’s Syndrome, are accompanied by reductions in the sensitivity of cells to the action of insulin.
The main glucocorticoid in man is cortisol, whereas in other mammals such as the rat, the main glucocorticoid can be corticosterone. Glucocorticoids are produced by the adrenal cortex in response to an exposure to a perceived environmental stressors. Stress therefore results in elevated levels of circulating glucocorticoids. Glucocorticoids regulate a number of systems including blood pressure, immune function and metabolism. They are also important in regulating the uptake and utilisation of glucose as a fuel. In this regard they oppose the action of insulin through induction of insulin resistance and may also reduce the release of insulin from the β-cells of the pancreas (although under some conditions they increase insulin release via stimulation of the vagal nerve). This explains the symptoms of excess cortisol in humans, that include central obesity, weight gain and glucose intolerance, as well as increased appetite. In fact, glucocorticoids were so named because of the observed relationship to glucose metabolism.
Studies have investigated the effects of glucocorticoids on insulin. From such studies it has become clear that the relationship between glucocorticoids and insulin sensitivity is complex. The main determinant of glucose sensitivity in cells is the presence of GLUT4 transporters of the membranes of the cells. While glucocorticoids increase the expression of GLUT4 transporters, they decrease their translocation to the cell membrane. Thus the facilitation of glucose to the interior of the cell is diminished with high circulating glucocorticoid levels. Glucocorticoids may also cause elevation in the amount of free fatty acids in circulation, through increased lipolysis, and this may contribute to the formation of insulin resistance. Glucocorticoids may also inhibit endothelium-dependent vasodilation, a process that increases glucose supply to peripheral tissues. In addition, glucocorticoids can alter hepatic glucose metabolism and in this respect may oppose or complement the action of insulin, however the exact effects are not clear.
Stress can therefore have significant effects on glucose metabolism and may be a significant driver of insulin resistance. Stress is an often overlooked factor in the development of Western lifestyle disease. In fact one of the ways that a high quality diet may protect from disease is through increasing the tolerance of the individual to environmental stress. In this way a high quality diet can limit the damage caused by external stressors that can lead to oxidative stress, immune dysfunction and metabolic perturbations. The ability of exercise to counter the effect of stress, partly through increasing the rate of metabolism and excretion of stress hormones, may explain the beneficial effects of exercise on insulin sensitivity. However, exercise itself can be a stress if performed to excess and so this beneficial effect likely occurs at lower to moderate levels of activity. Meditation, massage and other relaxation techniques may also counter the negative effects of stress and so may have beneficial effects on insulin sensitivity.
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