Insulin receptor and leptin

by Yecenia Arellano

We presented this week on a paper The role of insulin receptor signaling in the brain. we learned that Insulin enters the central nervous system through the blood brain barrier via a receptor mediated transport mechanism. Insulin receptors are found in highest concentrations in the olfactory bulb, hypothalamus, cerebral cortex, cerebellum, and hippocampus. By studying the effects of glucose in the brain they found that direct administration into the brain yielded an anorexigenic effect which resulted is weight loss. Where as inhibition of insulin resulted in an orexigenic effect and increase in body weight( just like in type 2 diabetes). The insulin receptors found within the hypothalamus play a role in regulating glucose in the periphery. They go into high detail in order to understand what exactly in the pathway is producing these effects with a series of knock in knock out experiments. Ultimately they go into why the insulin receptor is important in learning, memory, and its role in degenerative diseases. They found that intranasal administration of insulin produces an increases performance in learning tasks. Linking it back to Alzheimer’s, these patients have high insulin concentrations in their plasma as compared to the cerebral-spinal fluid, which they correlate as poor insulin metabolism in the brain that could lead to impairments. They also point out that Alzheimer’s and Parkinson’s patient did infact show a reduced expression of the insulin receptor.

We later learned about leptin and its implications. Leptin is the hormone responsible for inhibiting hunger and increasing energy expenditure. It is produced primarily within white adipose tissues. It also enhances insulin’s ability to suppress glucose production. Increased adiposity causes increase in plasma concentration which could lead to leptin resistance which in turm leads to increased body adiposity. The pathway:

There was an emphasis placed on POMC neurons which are responsible for releasing alpha-melanocyte stimulating hormone that affects the melanocortin receptors. This hormone is responsible for inhibiting food intake, increasing energy expenditure, and decreasing body weight. Leptin will act on these POMC neurons to activate them and produce the aforementioned results. On the opposite side insulin will hyperpolarize theses POMC neurons therefore inhibiting its effects. NPY and AgRP are peptides responsible for increase food intake, decrease in energy expenditure by inhibiting POMC neurons. Leptin will inhibit these NPY and AgRP neurons causing the opposite effect.

Both papers that were discussed this week showed that leptin and insulin share a pathway in which different effects are produced by either hormone. The major concept that was seen throughout was that all theses hormones and pathways work together in order to maintain homeostasis.