AUTONOMIC MEDIATION OF THE EFFECT OF RAISED ARTERIAL GLUCOSE UPON FREE FATTY ACIDS

Area of Science:

• Endocrinology
• Neuroscience
• Metabolic Research

Background:

• Fasting elevates free fatty acids (FFAs) due to sustained lipolysis.
• The autonomic nervous system plays a role in regulating lipolysis.
• The central nervous system's (CNS) role in glucose-mediated FFA reduction is not fully understood.

Purpose of the Study:

• To investigate the CNS mechanisms underlying the reduction of arterial free fatty acids (FFAs) following glucose infusion.
• To determine the involvement of the sympathetic nervous system in this glucose-induced FFA response.
• To assess the role of insulin secretion in mediating the effect of glucose on FFAs.

Main Methods:

• Intravenous glucose infusion (600 mg over 30 minutes) in overnight-fasted subjects.
• Administration of ganglionic or adrenergic blocking agents to assess autonomic and sympathetic nervous system involvement.
• Monitoring arterial blood glucose and free fatty acid concentrations.
• Evaluating insulin secretion in response to glucose infusions.
• Studying insulin-dependent diabetics primed with long-acting insulin.

Main Results:

• Glucose infusion caused a 17% decrease in arterial FFAs.
• This FFA reduction was abolished by ganglionic or adrenergic blockade, indicating sympathetic nervous system involvement.
• Small insulin secretion occurred, but the FFA response was observed in insulin-dependent diabetics when pre-treated with insulin.
• Even minor glucose elevations (3 mg%) triggered the FFA response, which was blocked by autonomic inhibitors.

Conclusions:

• A CNS mechanism exists that responds to arterial glucose elevations by inhibiting sympathetic tone.
• This CNS pathway partially reduces sympathetic-mediated lipolysis during fasting.
• The observed reduction in FFAs is primarily mediated by the central nervous system's influence on sympathetic outflow, rather than solely by insulin secretion.