• Alex Rafacho, Henrik Ortsäter, Angel Nadal, and Ivan Quesada.
• Department of Physiological SciencesCenter of Biological Sciences, Federal University of Santa Catarina (UFSC), 88040-900, Florianópolis, SC, BrazilDepartment of Clinical Science and EducationSödersjukhuset, Karolinska Institutet, SE-11883 Stockholm, SwedenInstitute of Bioengineering and the Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM)Miguel Hernández University, University Avenue s/n, 03202, Elche, Spain alex.rafacho@ufsc.br ivanq@umh.es.
• J. Endocrinol. 2014 Dec 1; 223 (3): R49-62.

AbstractGlucocorticoids (GCs) are broadly prescribed for numerous pathological conditions because of their anti-inflammatory, antiallergic and immunosuppressive effects, among other actions. Nevertheless, GCs can produce undesired diabetogenic side effects through interactions with the regulation of glucose homeostasis. Under conditions of excess and/or long-term treatment, GCs can induce peripheral insulin resistance (IR) by impairing insulin signalling, which results in reduced glucose disposal and augmented endogenous glucose production. In addition, GCs can promote abdominal obesity, elevate plasma fatty acids and triglycerides, and suppress osteocalcin synthesis in bone tissue. In response to GC-induced peripheral IR and in an attempt to maintain normoglycaemia, pancreatic β-cells undergo several morphofunctional adaptations that result in hyperinsulinaemia. Failure of β-cells to compensate for this situation favours glucose homeostasis disruption, which can result in hyperglycaemia, particularly in susceptible individuals. GC treatment does not only alter pancreatic β-cell function but also affect them by their actions that can lead to hyperglucagonaemia, further contributing to glucose homeostasis imbalance and hyperglycaemia. In addition, the release of other islet hormones, such as somatostatin, amylin and ghrelin, is also affected by GC administration. These undesired GC actions merit further consideration for the design of improved GC therapies without diabetogenic effects. In summary, in this review, we consider the implication of GC treatment on peripheral IR, islet function and glucose homeostasis. © 2014 Society for Endocrinology.

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