Señales De La Insulina

Archives of Physiology and Biochemistry, April 2006; 112(2): 82 – 88

REVIEW ARTICLE

Insulin signalling in human adipose tissue

LUIGI LAVIOLA, SEBASTIO PERRINI, ANGELO CIGNARELLI, & FRANCESCO GIORGINO
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Section of Internal Medicine, Endocrinology and MetabolicDiseases, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy

Abstract Adipose tissue is a critical regulator of energy balance and substrate metabolism, and synthesizes several different substances with endocrine or paracrine functions, which regulate the overall energetic homeostasis. An excessive amount of adipose tissue has been associated with the development oftype 2 diabetes, premature atherosclerosis, and cardiovascular disease. It is believed that the adverse metabolic impact of visceral fat relies on a relative resistance to the action of insulin in this depot compared to other adipose tissue depots. However, information on insulin signalling reactions in human fat is limited. In this paper, we review the major insulin signalling pathways inadipocytes and their relevance for metabolic regulation, and discuss recent data indicating different signalling properties of visceral fat as compared to other fat depots, which may explain the metabolic and hormonal specificity of this fat tissue depot in humans.

Key words: Insulin receptor, Akt, Erk, visceral fat, subcutaneous fat, adipocytes.

Biological functions of adipose tissue Adipose tissueis an important regulator of energy balance and substrate metabolism. The ‘classical’ function of fat is to regulate storage and utilization of energy in the triglycerides depots, under the control of insulin, catecholamines, and the autonomic nervous system. However, adipose tissue is not only responsible for storage of energy. Rather, it is a highly active and dynamic tissue involved in theinterplay between hormones, nerves and metabolism. Adipocytes produce several different substances with different endocrine or paracrine functions, such as leptin, which regulates energy balance by reducing food intake and increasing energy expenditure, and adiponectin, an adipocyte-derived plasma protein with insulin sensitising, anti-atherogenic and antiinflammatory properties (Ahima & Flier, 2000).Adipose tissue also synthesises and secretes cytokines, for example tumour necrosis factor alpha (TNF-a) and interleukin (IL) 6 and 8, that possess metabolic effects on the adipose tissue itself and probably also in other organs. Cytokines appear to be released from adipose tissue in response to inflammatory stimuli, and contribute to obesity-associated insulin resistance and metabolic derangement(Ahima & Flier, 2000). In addition, in adipose tissue biologically inactive cortisone can be converted to active cortisol by 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD-1) (Rask et al., 2001), and testosterone is converted to estrogens by aromatases (De Ronde et al., 2003). An excessive amount of adipose tissue has been associated with the development of type 2 diabetes, prematureatherosclerosis, and cardiovascular disease (National Task Force on the Prevention and Treatment of Obesity, 2000). The relationship between excessive fat and increased cardio-metabolic risk has not been fully elucidated, but it is increasingly apparent that accumulation of adipose tissue in the abdominal region, rather than excess body fat per se, is the key factor in determining the unfavourableoutcomes of obesity (Despres et al., 2001). Support for a specific adverse impact of abdominal fat also comes from studies in human and experimental insulin-resistance, in which surgical removal of visceral fat was followed by metabolic improvement, both in humans and in rodents (Thorne et al., 1994; Gabriely et al., 2002; Gabriely & Barzilai, 2003). Indeed, visceral adiposity, manifested as a high...