Effects of glucagon as a neurohormone on the central nervous system and glucose homeostasis.

OBJECTIVE: This study aimed to elucidate the possible effects of the acute/long-term infusion of glucagon in the brain as the regulatory role on the endocrine secretions of the pancreas.

MATERIALS AND METHODS: Ninety male Wistar albino rats were divided as Control, artificial Cerebrospinal Fluid (aCSF) (120 min), Glucagon (120 min), pancreatic denervation (PD)+aCSF (120 min), PD+Glucagon (120 min), aCSF (7 days), Glucagon (7 days), PD+aCSF (7 days) and PD+Glucagon (7 days). Glucagon and solvent (aCSF) were administered after pancreatic denervation (PD) by Hamilton syringe and osmotic mini pump (1 µg/10 µl/min) in the third ventricle of the brain.

RESULTS: Acute intracerebroventricular (icv) administration of glucagon resulted in an elevation of glucagon levels and a concurrent reduction in blood glucose levels. Furthermore, in both the PD+aCSF (7 days) and PD+Glucagon (7 days) groups, there was a notable decrease in propiomelanocortin (POMC) and agouti-related protein (AgRP). Significant changes were observed in feed consumption and body weight, as well as pancreatic glucagon levels, with a simultaneous decrease in insulin levels in the PD (7 days), Glucagon (7 days), and PD+Glucagon (7 days) groups. These alterations were statistically significant when compared to the control group (p<0.05).

CONCLUSIONS: The research outcomes established that pancreas-secreted glucagon functions as a neurohormone within the brain, activating central pathways linked to blood glucose regulation. The presence of glucagon led to a decrease in POMC levels. Surprisingly, this reduction in POMC resulted in the suppression of AgRP. Contrary to expectations, the suppression of AgRP led to an increase in food intake rather than a decrease. As already highlighted in the results section, it was emphasized that POMC may play a more significant role than AgRP in influencing feeding behavior.