Early endocrine and molecular changes in metabolic syndrome models

Abstract

SummaryThe twenty-first century arrived in the middle of a global epidemic of metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). It is generally accepted that an excess of nutrients linked to a low physical activity triggers the problem. However, the molecular features that interact to develop the MS are not clear. In an effort to understand and control them, they have been extensively studied, but this goal has not been achieved yet. Nonhuman animal models have been used to explore diet and genetic factors in which experimental conditions are controlled. For example, only one factor in the diet, such as fats or carbohydrates can be modified to better understand a single change that would be impossible in humans. Most of the studies have been done in rodents. However, it is difficult to directly compare them, because experiments are different in more than one variable; genetic strains, amount, and the type of fat used in the diet and sex. Thus, the only possible criteria of comparison are the relevance of the observed changes. We review different animal models and add some original observations on short-term changes in metabolism and beta cells in our own model of adult Wistar rats that are not especially prone to get fat or develop DM2, treated with 20% sucrose in drinking water. One early change observed in pancreatic beta cells is the increase in GLUT2 expression that is located to the membrane of the cells. This change could partially explain the presence of insulin hypersecretion and hyperinsulinemia in these rats. Understanding early changes that lead to MS and in time to pancreatic islet exhaustion is an important biomedical problem that may contribute to learn how to prevent or even reverse MS, before developing DM2.

Liraglutide Compromises Pancreatic β Cell Function in a Humanized Mouse Model

“…These findings are consistent with the notion that “excessive” activation of an already overworked beta cell under diabetic conditions during long-term treatment with incretin mimetics may lead to metabolic exhaustion of the beta cell (Araki et al, 2003; Larque et al, 2011) and, ultimately, compromised glucose homeostasis. This is conceptually important to consider prior to prescribing long-term multi-year continuous usage of GLP-1 analogs for the treatment of T2D.…”

Hyperinsulinemia is Associated with Increased Soluble Insulin Receptors Release from Hepatocytes

“…We used a model of MS in adult male Wistar rats as previously reported by our group (19). Briefly, MS was induced in 2-months-old rats by a hypercaloric diet over 8 weeks, which consisted of a 20% (w/v) sucrose solution as drinking water.…”

“…This effect could be partially prevented by inhibiting protease activity. To test if a similar process could be present in the whole animal, we used a rat model of MS (19, 20) that presents hyperinsulinemia. We observed that levels of circulating SIR were increased.…”

Metabolic syndrome induces changes in KATP-channels and calcium currents in pancreatic β-cells

“…According to the definition of metabolic syndrome, all these changes indicate that the high-carbohydrates intake is sufficient to develop metabolic syndrome, as previously observed with a two months long treatment. 4 Since Reaven's metabolic syndrome description, 12 insulin resistance has been proposed as the key issue to understand its etiology. At present, it is well accepted that abdominal fat is frequently linked to insulin resistance and therefore obesity has been considered a risk factor for developing MS (for a review, see subpopulation 10.3 ± 0.6 was found compared with the others (Fig.…”

“…Hyperinsulinemia and insulin resistance are key issues to understanding MS. 3 We recently described that exposing Wistar young adult male rats to high sucrose in drinking water for two months induces MS. 4 Glucose-induced insulin secretion is a complex process of signal transduction in β cells, comprised by proximal events, which include glucose internalization through GLUT2 transporters and glucose metabolism that increase the ATP/ADP relationship, and by distal events, which include the activation of different ionic channels. Distal events start with the closure of ATP-sensitive Metabolic syndrome (MS) can be defined as a group of signs that increases the risk of developing type 2 diabetes mellitus (DM2).…”