Lipocalins and insulin resistance: etiological role of retinol-binding protein 4 and lipocalin-2?

摘要

The prevalence of type 2 diabetes is increasing dramatically worldwide. Excess adiposity is an important contributor to the development of type 2 diabetes and cardiovascular diseases (1). Insulin resistance, inflammation, hypertension, and dyslipidemia, components of the metabolic syndrome, have been implicated in the effects of adiposity on type 2 diabetes and cardiovascular diseases, but the mechanisms responsible for these detrimental effects of adiposity have not been fully elucidated. Two paradigms are currently areas of intense study: one focused on ectopic fat and the other on the endocrine function of adipose tissue (2). Ectopic fat is present in nonadipose tissues such as the liver, muscle, and probably pancreatic beta-cells. Both lipodystrophy (failure to develop adipose tissue) and obesity with full adipose cells are characterized by a lack of fat-storage capacity, resulting in overflow to other tissues of triglycerides and free fatty acids in the form of ectopic fat. Normal physiological processes can be disrupted by this ectopic fat, leading to insulin resistance and impaired insulin secretion. The endocrine function of adipose tissue is an important regulatory process throughout the body that is carried out by signaling proteins secreted by adipose tissue. These signaling proteins are called adipocytokines or adipo-kines, and they include leptin, adiponectin, resistin, tumor necrosis factor-alpha, and interleukin-6.