The autonomic nervous system regulates glucose and lipid metabolism

The review reports that brain insulin action and autonomic nervous system signalling influence insulin secretion, postprandial hepatic glucose production and lipid handling. It also describes opposing roles of the sympathetic and parasympathetic branches across the pancreas, liver and adipose tissue.

This review examines how the autonomic nervous system (ANS) coordinates glucose and lipid metabolism across multiple organs and how circulating and brain-acting hormones interact with these neural pathways. It highlights human and animal evidence that insulin acting in the brain, including via intranasal administration in humans, affects peripheral metabolism and autonomic tone. The article describes opposing actions of the sympathetic and parasympathetic branches on the pancreas, liver and adipose tissue, and it outlines links between autonomic signalling and immune activity. Several findings rely on human studies while others are drawn from animal experiments and remain under active investigation. Key points: - Brain insulin action, studied in humans using intranasal insulin, promotes a shift toward parasympathetic tone and has been reported to improve peripheral insulin sensitivity and to suppress endogenous hepatic glucose production in the postprandial state. - The pancreas is directly modulated by both ANS branches: sympathetic signalling generally inhibits insulin secretion via α-adrenoceptors in the fasted state and can enhance glucagon via β-adrenergic pathways, while parasympathetic (vagal) input stimulates insulin secretion through acetylcholine acting on muscarinic receptors. - In the liver, sympathetic activation stimulates glycogen breakdown and gluconeogenesis, whereas parasympathetic activity enhances glycogen synthesis and inhibits glucose production; autonomic signals also affect hepatic lipid handling and VLDL secretion. - Sympathetic nerves drive lipolysis in human adipose tissue through β-adrenergic receptors; clear parasympathetic innervation of adipose tissue in humans is not established, and indirect parasympathetic effects occur via insulin release. - The ANS interacts with the immune system: sympathetic signalling can be context-dependent and bidirectional for inflammation, while parasympathetic pathways (the cholinergic anti-inflammatory pathway) are described as anti-inflammatory in several experimental settings. Summary: The review brings together evidence that the ANS and brain-acting hormones coordinate systemic glucose and lipid metabolism through organ-specific, often opposing sympathetic and parasympathetic actions. Some mechanisms are demonstrated in humans (for example, effects of intranasal insulin on peripheral metabolism) while others are supported mainly by animal studies. Undetermined at this time.