Insulin has long been recognized as a major endocrine regulator of the uptake, cellular transport, and intermediary metabolism of small nutrient molecules such as amino acids, fatty acids, and glucose1. Adipose tissue and skeletal muscle are the classical major target of insulin action; the CNS, in contrast, has traditionally been considered to be largely insulin-insensitive. However, clues that insulin may have physiological functions in the CNS began to emerge in the 1960s, and an impressive body of literature has since accumulated about insulin in the CNS. Although insulin now regularly appears in litanies cataloging CNS peptides, its status as a CNS regulatory peptide remains obscure and elusive. The situation has become more clouded with the recent discovery that insulin-like growth-factors (IGFs) and their receptors are also present in the CNS. Since IGFs and insulin share similar primary amino acid structure, receptor binding, and biological activity2, any discussion about insulin as a CNS regulatory peptide must also consider the IGFs. In the present article, we summarize the status of insulin and IGFs as regulatory peptides in the CNS. Our choice of literature has been selective, with a focus on recent reports, controversial issues, and unsolved problems. Readers are referred to previous reviews for much of the earlier literature1-5.
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