Insulin: A connection between pancreatic β cells and the hypothalamus

Abstract

Insulin is a hormone secreted by pancreatic β cells. The concentration of glucose in circulation is proportional to the secretion of insulin by these cells. In target cells, insulin binds to its receptors and activates phosphatidylinositol-3-kinase/protein kinase B, inducing different mechanisms depending on the cell type. In the liver it activates the synthesis of glycogen, in adipose tissue and muscle it allows the capture of glucose, and in the hypothalamus, it regulates thermogenesis and appetite. Defects in insulin function [insulin resistance (IR)] are related to the development of neurodegenerative diseases in obese people. Furthermore, in obesity and diabetes, its role as an anorexigenic hormone in the hypothalamus is diminished during IR. Therefore, hyperphagia prevails, which aggravates hyper-glycemia and IR further, becoming a vicious circle in which the patient cannot regulate their need to eat. Uncontrolled calorie intake induces an increase in reactive oxygen species, overcoming cellular antioxidant defenses (oxidative stress). Reactive oxygen species activate stress-sensitive kinases, such as c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, that induce phos-phorylation in serine residues in the insulin receptor, which blocks the insulin signaling pathway, continuing the mechanism of IR. The brain and pancreas are organs mainly affected by oxidative stress. The use of drugs that regulate food intake and improve glucose metabolism is the conventional therapy to improve the quality of life of these patients. Currently, the use of antioxidants that regulate oxidative stress has given good results because they reduce oxidative stress and inflammatory processes, and they also have fewer side effects than synthetic drugs.

Keywords: Insulin; Pancreas; Hypothalamus; Hyperphagia; Hyperglycemia; Stress

Core Tip: Insulin is the connection between the β cells of the pancreas and the hypothalamus. Insulin reaches the arcuate nucleus of the hypothalamus and represses the expression of orexigenic neuropeptides to suppress appetite. However, its function decreases when there is damage to the β cells of the pancreas. Its anorexigenic effect decreases and thus increases appetite. The excess of nutrients, specifically carbohydrates, aggravates the damage to β cells and induces obesity and/or diabetes and oxidative damage. The use of antioxidants constitutes a therapeutic approach that has been approached experimentally to regulate the negative effects of alterations in insulin secretion and function.