Changes in Insulin Secretion and Glucose Metabolism Induced by Dexamethasone in Lean and Obese Females

Abstract

BESSE, CHRISTINE, NATHALIE NICOD, AND LUC TAPPY. Changes in insulin secretion and glucose metabolism induced by dexamethasone in lean and obese females. Obes Res. 2005;13:306 -311. Objective: In healthy lean individuals, changes in insulin sensitivity occurring as a consequence of a 2-day dexamethasone administration are compensated for by changes in insulin secretion, allowing glucose homeostasis to be maintained. This study evaluated the changes in glucose metabolism and insulin secretion induced by short-term dexamethasone administration in obese women. Research Methods and Procedures: Eleven obese women with normal glucose tolerance were studied on two occasions, without and after 2 days of low-dose dexamethasone administration. A two-step hyperglycemic clamp (7.5 and 10 mM glucose) with 6,6 2 H 2 glucose was used to assess insulin secretion and whole body glucose metabolism. Results were compared with those obtained in a group of eight lean women. Results: Without dexamethasone, obese women had higher plasma insulin concentrations in the fasting state, during the first phase of insulin secretion, and at the two hyperglycemic plateaus. However, they had normal whole body glucose metabolism compared with lean women, indicating adequate compensation. After dexamethasone, obese women had a 66% to 92% increase in plasma insulin concentrations but a 15.4% decrease in whole body glucose disposal. This contrasted with lean women, who had a 91% to 113% increase in plasma insulin concentrations, with no change in whole body glucose disposal. Discussion: Dexamethasone administration led to a significant reduction in whole body glucose disposal at fixed glycemia in obese but not lean women. This indicates that obese women are unable to increase their insulin secretion appropriately.

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

“…Therefore, the insulinogenic index may not necessarily match the peripheral insulin demand imposed by GCs. The negative impact of GCs on glucose homeostasis is more apparent in individuals or rodents with any degree of susceptibility to glucose intolerance, such as those with low insulin sensitivity (Larsson & Ahrén 1999), low insulin response to glucose (Wajngot et al 1992), first-degree relatives of patients with type 2 diabetes (Jensen et al 2012), obesity (Besse et al 2005) and those who are older (Novelli et al 1999). In these contexts, b-cell function does not correspond to the peripheral insulin demand, and the deregulation of glucose homeostasis becomes more pronounced, reinforcing that individual background is a critical factor.…”

Impact of glucocorticoids on insulin resistance in the critically ill

“…In addition, endogenous glucose production is enhanced by glucocorticoids [9,[12][13]34], possibly through their enhancement of the synthesis and action of catecholamines [19,32,[35][36].…”

Functional and Molecular Aspects of Glucocorticoids in the Endocrine Pancreas and Glucose Homeostasis

“…However, it is also known that GCs, by direct effects, can cause pancreatic -cell dysfunction, which leads to attenuated GSIS (Lambillotte et al, 1997;Jeong et al, 2001;Ullrich et al, 2005;Zawalich et al, 2006;Roma et al, 2011). The crucial point is that, at least during short (2 to 15 days) periods of treatment, the direct negative effects of GCs are not reproduced on pancreatic -cell during in vivo GC administration to normal subjects, and the derangement of -cells during GC treatment seems to depend on predispositions such as genetic background (Ogawa et al, 1992), age (Novelli et al, 1999) as well as previous glucose intolerance and/or low insulin sensitivity (Wajngot et al, 1992;Ohneda et al, 1993;Henriksen et al, 1997;Larsson & Ahren, 1999;Besse et al, 2005). In the next topic, we will discuss in detail the endocrine pancreas and glucose homeostasis profile both in human and in rodent experimental models of GC treatment.…”

“…Administration of GCs to individuals with any degree of susceptibility towards glucose intolerance, but still normoglycemic, before treatment with GCs, such as those with low insulin sensitivity (Larsson & Ahren, 1999) or with low insulin response to glucose (Wajngot et al, 1992), obese women (Besse et al, 2005) and first-degree relatives of patients with type 2 diabetes mellitus (T2DM) (Henriksen et al, 1997), fails to induce the adaptive islet compensation observed in healthy subjects. Thus, in such individuals GC treatment may disrupt glucose homeostasis and cause hyperglycemia.…”

“…Thus, in such individuals GC treatment may disrupt glucose homeostasis and cause hyperglycemia. The derangements that contribute to glucose intolerance include reduction in glucose-dependent or arginine-induced insulin release (Larsson & Ahren, 1999), increased glucose production and decreased glucose clearance (Wajngot et al, 1992), and reduction in whole body glucose disposal (Besse et al, 2005). Therefore, the enhancement in -cell response, required to accommodate the GCinduced IR state, is impaired in these subjects.…”