The seminal concept proposed by Sir Harold Himsworth more than 75 years ago that a large number of patients with diabetes were '
insulin insensitive', now termed
insulin resistance, has now expanded to include several endocrine syndromes, namely those of
glucocorticoid excess, and
growth hormone excess and deficiency. Synthetic
glucocorticoids are increasingly used to treat a wide variety of
chronic diseases, whereas the beneficial effects of
recombinant growth hormone replacement
therapy in children and adults with
growth hormone deficiency have now been well-recognized for over 25 years. However, clinical and experimental studies have established that increased circulating levels of
glucocorticoids and
growth hormone can also lead to worsening of
insulin resistance,
glucose intolerance, overt
diabetes mellitus and
cardiovascular disease. Improved understanding of the physiological 24-h rhythmicity of
glucocorticoid and
growth hormone secretion and its influence on the dawn phenomenon and the Staub-Trauggot effect has therefore led to renewed interest in studies on the mechanisms of
insulin resistance induced by exogenous administration of
glucocorticoids and
growth hormone in humans. In this review, we describe the physiological events that result from the presence of resistance to
insulin action at the level of skeletal muscle, adipose tissue, and liver, describe the known mechanisms of
glucocorticoid- and
growth hormone-mediated
insulin resistance, and provide an update of the contributions of
glucocorticoids and
growth hormone to understanding the pathophysiology of
insulin resistance and its effects on several endocrine syndromes.