Functional Alterations in Endocrine Pancreas of Rats With Different Degrees of Dexamethasone-Induced Insulin Resistance

Abstract

We demonstrate that in DEX 0.5 and, especially in DEX 0.1 groups, but not in DEX 1.0, the adaptations that occurred in the endocrine pancreas are able to counteract metabolic disorders (glucose intolerance and dyslipidemia). These animal models seem to be interesting approaches for the study of degrees of subjacent effects that may mediate type 2 diabetes (DEX 1.0) and islet function alterations, without collateral effects (DEX 0.1 and DEX 0.5).

Reduced pancreatic β-cell mass is associated with decreased FoxO1 and Erk1/2 protein phosphorylation in low-protein malnourished rats

“…Among these alterations, reduction in β-cell mass and proliferation has been reported, as well as diminished islet vascularization (1)(2)(3)(4). Changes in peripheral insulin sensitivity are compensated by reciprocal alterations in islet mass and function (10)(11)(12)(13). The interaction between the systemic requirement for insulin and islet function guarantees that blood glucose is kept within physiological ranges in rats when malnutrition is induced by a low-protein diet (6,7).…”

Regulation of Glucocorticoid Receptor Signaling and the Diabetogenic Effects of Glucocorticoid Excess

“…Despite their excellent effects for the treatment of inflammatory and allergic diseases, GCs use is limited by their side effects on several systems, organs and/or tissues (Table 1), which are dependent on the dose and duration of the GC treatment. Among these adverse effects are the endocrine derangements that include increase in central fat deposition Asensio et al, 2004), hyperphagia (Debons et al, 1986), hepatic steatosis , dyslipidemia characterized by increased TG and nonesterified fatty acid (NEFA) levels (Taskinen et al, 1983;Rafacho et al, 2008), muscle atrophy (Prelovsek et al, 2006), IR and/or glucose intolerance (Stojanovska et al, 1990;Binnert et al, 2004;Rafacho et al, 2008), as well as overt diabetes in susceptible individuals (Schacke et al, 2002).…”

Insulin signaling proteins in pancreatic islets of insulin-resistant rats induced by glucocorticoid

“…injection of 1mg/kg b.w. dexamethasone (DEX rats) or saline -NaCl 0.9% -(CTL rats), between 7:30 -8:30 h, for 5 consecutive days (Rafacho et al, 2008a).…”

“…It has been proposed that hyperinsulinemia in dexamethasonetreated individuals is a compensatory mechanism of the endocrine pancreas to counteract insulin resistance (Karlsson et al, 2001;Nicod et al, 2003;Rafacho et al, 2010a). The mechanisms that support the increased circulating insulin levels under insulin resistance include the augment in islet response to metabolic and nonmetabolic signals, especially glucose (Karlsson et al, 2001;Rafacho et al, 2008a) and an increase in β-cell proliferation and mass (Rafacho et al, 2008b;Rafacho et al, 2009). …”

“…Administered in excess, dexamethasone can induce adverse effects such as peripheral insulin resistance (Stojanovska et al, 1990;Binnert et al, 2004;Korach-André et al, 2005). Based on this information, dexamethasone is used as a tool for the induction of experimental insulin resistance in rodents (Stojanovska et al, 1990;Korach-André et al, 2005;Burén et al, 2008;Rafacho et al 2008a;Rafacho et al, 2010a) and transitory insulin resistance in humans (Beard et al, 1984;Nicod et al, 2003;Binnert et al, 2004) and in rodents (Rafacho et al, 2010b).…”