La tormentosa relación entre las grasas y el desarrollo de la diabetes mellitus de tipo 2: actualizado. Parte 1

Abstract

A review is presented on a functional relationship between fat and carbohydrate metabolism and inter-dependence from the traditional concepts of glucose-fatty acids cycle (Randle), and from the insulin resistance portal hypothesis up to the new aspects on brown and beige adipocytes. Emphasis is placed on the normal function of an endocrine pattern, in which its malfunction is the key in the pathophysiology of these conditions: the adipoinsular axis, with a functional link with the hypothalamic-pituitary-adrenal axis, which involves 2 adipogenic hormones (insulin and glucocorticoid). This has an influence on the development of omental peri-visceral fat, with severe metabolic consequences. A discussion is also presented on the concept of ectopic fat on non-adipose tissues that results in the incapacity of fatty tissue for storing lipids and the considerations about the endocrine activity of adipocyte producing substances that influence several mechanisms that could result in insulin resistance (leptin, adiponectin, TNF-α, resistin, etc.). New aspects are considered regarding the decrease in the oxidative capacity in the mitochondrial respiratory chain, and the re-birth of the concept of de novo lipogenesis that increases the storing of intra-cellular fat. In non-adipose tissues there are small intra-cellular fat quantities for essential functions, but lipid overloading leads to cell dysfunction (lipo-toxicity) and death (lipo-apoptosis). The stormy relationship between fat and Langerhans’ Islets goes beyond the functional effort as consequence of peripheral insulin-resistance and the pancreatic beta cell suffers a direct lipid (or derivatives) functional effect. Without insulin deficiency diabetes does not appear.