The Importance of Adrenomedullin (AM) on ACTH-Cortisol-Glucose Axis

Overview

Hyperglycemia is frequent manifestations of the human metabolic response to systemic inflammatory response syndrome (SIRS),sepsis and septic shock, and are implicated in the clinical outcome. Adrenomedullin is elevated in SIRS, sepsis and septic shock and has been demonstrated the inhibitory role on insulin and adrenocorticotropic hormone secretion. Our hypothesis is that: AM elevation after SIRS could be the responsible to maintain hyperglycemia

Studies in cultured vascular endothelial cells and vascular smooth muscle cells demonstrate that cytokines strongly stimulate adrenomedullin production and release. Adrenomedullin has been measured in a wide range of clinical researches. Of all conditions investigated, the greatest increment in plasma adrenomedullin has been observed in septic shock. It appears that AM is directly responsible for the hypotension characteristic of septic shock. Studies have shown that administration of AM and AMBP-1 before the onset of sepsis (i.e., pretreatment) prevents transition from the hyperdynamic phase to the hypodynamic phase in the progression of sepsis, attenuates tissue and organ damage, and reduces sepsis-induced mortality. Two groups described the effects of AM on the pituitary. Taken together, these studies suggest that AM has a role in inhibiting ACTH release. Mulder et al. first reported the stimulatory effects of adrenomedullin on insulin secretion from isolated rat islets. In direct contrast to this, Martínez et al. clearly demonstrated the inhibitory role of adrenomedullin on insulin secretion in vitro.

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