Our current understanding of the pituitary indicates that Proopiomelanocortin (POMC) pituitary cells are controlled entirely by the hypothalamic endocrine system and by feedback signals from hypothalamic circuits, the pituitary, and specific peripheral organs. However, it is plausible that direct regulation of anterior lobe (AL) pituitary cells by blood glucose exists, because glucose-sensing cells are found in the AL of the pituitary.
The studies of Enriori, Chen et al. describe a new endocrine circuit that is capable of modulating post-prandial glucose homeostasis. The authors demonstrate that in humans, non-human primates, and mice, the pituitary detects circulating glucose and responds with increased α-melanocyte stimulating hormone (α -MSH) secretion. Overall, this is the first report showing that the increase in plasma α-MSH exclusively enhances muscle glucose uptake through the direct activation of canonical melanocortin 5 receptor (MC5R)-PKA pathways in muscle of lean but not obese subjects. Inhibition of phosphodiesterase restores α-MSH mediated glucose tolerance in obese mice. This discovery provides the basis for future studies to determine how melanocortin control of muscle glucose uptake and glycolysis can be utilized in treating patients with obesity and type 2 diabetes.
The cover image shows a microphotograph of a Japanese macaque pituitary.