Insulin receptors and insulin action in the brain: review and clinical implications
Introduction
Insulin receptors are widely dispersed throughout tissues of the periphery, and their function is well known — namely, mediation of glucose transport into cells. The existence of insulin receptors within the brain is less well known, and the function of these receptors is somewhat of an enigma. It is noteworthy that brain cells are not fully reliant upon insulin for glucose supply, i.e. they have insulin-independent means of obtaining glucose. Also, brain insulin receptors (InsRb) differ somewhat from their peripheral counterparts. What then is the physiological role of insulin receptors in the brain? The answer appears to be two-fold: (1) for tight control of glucose transport in specific brain regions, and (2) for as yet incompletely understood function in central nervous system (CNS) development and function. Aberrant function of the InsRb has been hypothesized to be involved in CNS dysfunction.
Section snippets
Rats
It might be expected that insulin receptors would be evenly distributed throughout all regions of the brain, particularly if their only function was to mediate insulin-induced glucose transport into neurons as a source of energy, and not as a signal-transduction pathway. In fact, insulin receptor density within the CNS is distributed irregularly and in distinct regional patterns. In rat brains, the highest InsRb densities are found in the olfactory bulb, cerebral cortex, hypothalamus,
Clinical implications
As summarized in the previous sections, neurons rely on glucose for energy, but only a small percentage of the glucose supply to neurons is delivered via insulin-dependent transport mechanisms. The rest of the glucose is obtained through non-insulin-dependent mechanisms. Further, insulin receptors are found in high density in some regions of brain, but in only low density in other regions of the brain [2], [3]. This uneven distribution is somewhat correlated with neuronal activity [1] and,
Summary
Brain insulin receptors, which are structurally slightly different from peripheral insulin receptors, are present — but not evenly distributed — throughout the brain. There are suggestions that the role of these receptors exceeds mediation of insulin utilization. First, the distribution of InsRb in the brain is neither homogeneous nor a simple function of glucose-utilization (energy-demand) patterns, second, InsRb have been shown to be present on synapses, and third, InsRb modulates
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