ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This review describes progress of our understanding of insulin action in the brain, as well as the consequences of brain insulin resistance. Insulin resistance of the brain results in impaired modulation of peripheral metabolism, the maintenance of obesity and an unfavorable body fat distribution. Current evidence suggest that brain insulin resistance is a treatable condition, thereby improving systemic metabolism and brain functions including cognition.

The human brain plays a central role in the regulation of glucose and lipid metabolism, body weight and fat distribution. When insulin is administered transnasally, it reaches the brain and has dose-dependent effects there, particularly in the hypothalamus. This influences lipid metabolism, such as fat distribution, and is important for homeostasis, food intake and cognition.

The human brain can suppress endogenous glucose production and stimulate glucose uptake in peripheral tissues such as muscles and adipocytes. It also influences insulin secretion by the pancreas. After food intake, insulin enters the brain, which sends signals to the periphery to suppress glucose production in the liver and promote insulin secretion. Disruptions in these signaling pathways can lead to a high risk of complications and increased mortality. The question how these signals are transmitted from the brain to peripheral tissues is key to understanding metabolic regulation.