Jose Donato Jr. Pages 2070 - 2081 ( 12 )
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.
brain, drugs, hypothalamus, insulin, insulin resistance, leptin, diabetes mellitus (T2DM), hyperglycemia, glucose homeostasis, synthetic drugs, tissues.
University of Sao Paulo, Institute of Biomedical Sciences, Department of Physiology and Biophysics, Av. Prof. Lineu Prestes, 1524, room 234, Sao Paulo, SP, Brazil, 05508-000.