Most of the drugs available to treat type 2 diabetes mellitus (T2DM) act either in the pancreas by increasing insulin
secretion or in tissues such as the liver or muscle by improving insulin sensitivity. However, recent studies have
shown that the brain also plays a critical role in the regulation of glucose homeostasis. For example, central leptin administration
reduces hyperglycemia and improves the survival of mice with type 1 diabetes mellitus (T1DM). In addition, several
pieces of evidence show that the brain can control the insulin sensitivity in different tissues and the pancreatic secretion
of insulin and glucagon. Therefore, the brain emerges as a promising new target of drugs aiming to treat both T1DM
and T2DM. An exciting finding is that there is a partial overlap between neuronal populations that regulate energy balance
and glucose homeostasis. Therefore, obesity and T2DM may have similar origins that are related to dysfunctions in the
central nervous system. Likewise, future drugs that target the brain to treat T2DM may have beneficial effects in reducing
body weight, and vice versa. In this review, the recent data showing how the brain is able to have an important regulatory
effect over blood glucose levels as well as the possible neuronal circuitries involved in the control of glucose homeostasis
will be summarized. The opportunities and challenges of using synthetic drugs or natural compounds that act in the central
nervous system to treat diabetes mellitus will also be discussed.
Keywords: brain, drugs, hypothalamus, insulin, insulin resistance, leptin, diabetes mellitus (T2DM), hyperglycemia, glucose homeostasis, synthetic drugs, tissues.
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