Title:Insulin and the Brain
Volume: 9
Issue: 2
Author(s): Fatemeh Derakhshan and Cory Toth
Affiliation:
Keywords:
Central nervous system diseases, Diabetes, Food intake, Insulin, Intranasal delivery, Memory.
Abstract: Mainly known for its role in peripheral glucose homeostasis, insulin has also significant impact within the
brain, functioning as a key neuromodulator in behavioral, cellular, biochemical and molecular studies. The brain is now
regarded as an insulin-sensitive organ with widespread, yet selective, expression of the insulin receptor in the olfactory
bulb, hypothalamus, hippocampus, cerebellum, amygdala and cerebral cortex. Insulin receptor signaling in the brain is
important for neuronal development, glucoregulation, feeding behavior, body weight, and cognitive processes such as
with attention, executive functioning, learning and memory. Emerging evidence has demonstrated insulin receptor signaling
to be impaired in several neurological disorders. Moreover, insulin receptor signaling is recognized as important for
dendritic outgrowth, neuronal survival, circuit development, synaptic plasticity and postsynaptic neurotransmitter receptor
trafficking. We review the multiple roles of insulin in the brain, as well as its endogenous trafficking to the brain or its exogenous
intervention. Although insulin can be directly targeted to the brain via intracerebroventricular (ICV) or intraparenchymal
delivery, these invasive techniques are with significant risk, necessitating repeated surgical intervention and
providing potential for systemic hypoglycemia. Another method, intranasal delivery, is a non-invasive, safe, and alternative
approach which rapidly targets delivery of molecules to the brain while minimizing systemic exposure. Over the last
decades, the delivery of intranasal insulin in animal models and human patients has evolved and expanded, permitting
new hope for associated neurodegenerative and neurovascular disorders.
