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

Rafacho, Alex; Ortsäter, Henrik; Nadal, Ángel; Quesada, Iván

doi:10.1530/joe-14-0373

Cited by 177 publications

(140 citation statements)

References 115 publications

(158 reference statements)

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…Herein, we suggest that hypercorticosteronemia associated with hyperactivity of vagus nerves contributes to functional changes in pancreatic β-cells in MSG-obese rats. In fact, as previously reported, hyperactivity of vagus nerves reduces apoptosis and increases proliferation in pancreatic β-cells (Medina et al 2013), and excessive corticosteroids induce β-cell proliferation leading to insulin oversecretion (Rafacho et al 2014).…”

Section: Figurementioning

confidence: 60%

“…Surgery causes blunting of ACh release in pancreatic β-cell neuronal ends, which reduces the cholinergic response of glucose-induced insulin secretion (GIIS) (Henquin 2000). Glucocorticoids induce gluconeogenesis, which supports high blood glucose levels in humans and rodents submitted to chronic treatment with glucocorticoids (Rafacho et al 2014). High HPA axis activity induces an enhancement of insulin secretion.…”

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

Miranda

Torrezan

Oliveira

et al. 2016

Journal of Endocrinology

View full text Add to dashboard Cite

Neuroendocrine dysfunctions such as the hyperactivity of the vagus nerve and hypothalamus–pituitary–adrenal (HPA) axis greatly contribute to obesity and hyperinsulinemia; however, little is known about these dysfunctions in the pancreatic β-cells of obese individuals. We used a hypothalamic-obesity model obtained by neonatal treatment with monosodiuml-glutamate (MSG) to induce obesity. To assess the role of the HPA axis and vagal tonus in the genesis of hypercorticosteronemia and hyperinsulinemia in an adult MSG-obese rat model, bilateral adrenalectomy (ADX) and subdiaphragmatic vagotomy (VAG) alone or combined surgeries (ADX–VAG) were performed. To study glucose-induced insulin secretion (GIIS) and the cholinergic insulinotropic process, pancreatic islets were incubated with different glucose concentrations with or without oxotremorine-M, a selective agonist of the M3muscarinic acetylcholine receptor (M3AChR) subtype. Protein expression of M3AChR in pancreatic islets, corticosteronemia, and vagus nerve activity was also evaluated. Surgeries reduced 80% of the body weight gain. Fasting glucose and insulin were reduced both by ADX and ADX–VAG, whereas VAG was only associated with hyperglycemia. The serum insulin post-glucose stimulation was lower in all animals that underwent an operation. Vagal activity was decreased by 50% in ADX rats. In the highest glucose concentration, both surgeries reduced GIIS by 50%, whereas ADX-VAG decreased by 70%. Additionally, M3AChR activity was recovered by the individual surgeries. M3AChR protein expression was reduced by ADX. Both the adrenal gland and vagus nerve contribute to the hyperinsulinemia in the MSG model, although adrenal is more crucial as it appears to modulate parasympathetic activity and M3AChR expression in obesity.

show abstract

Section: Figurementioning

confidence: 60%

Section: Figurementioning

confidence: 99%

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

Miranda

Torrezan

Oliveira

et al. 2016

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…11 Rafacho et al suggested a strong relationship between peripheral insulin resistance and glucose homeostasis imbalance. 12 The role of serum fructosamine and FBG in elevated glucose homeostasis has been documented in the literature. 13 Therefore, the present study examined the association of serum fructosamine and FBG with major depressive disorder (MDD).…”

Section: Resultsmentioning

confidence: 99%

The relationship between major depressive disorders and glucose parameters: A cross-sectional study in Chinese population

2017

View full text Add to dashboard Cite

Background. Depressive symptoms have been linked with insulin resistance in middle-aged and elderly populations. A strong relationship between peripheral insulin resistance and glucose homeostasis imbalance has been well established in previous studies. The role of serum fructosamine and fasting blood glucose (FBG) in elevating glucose homeostasis has been documented in the literature.Objectives. The aim of the study was to examine the association of serum fructosamine and FBG with major depressive disorder (MDD). Material and methods.The study analyzed the clinical characteristics and biochemical parameters of 305 patients with MDD and 312 healthy individuals.Results. Serum concentrations of lipoprotein-cholesterol (HDL-C), total protein (TP) and creatinine (Cr) were found to be significantly different between the two groups. Serum fructosamine and fasting blood glucose (FBG) concentrations were high in patients with MDD compared with healthy individuals (2.3 ± 0.26 vs. 2. 1 ± 0.27, p = 0.018; 4.7 ± 0.45 vs. 4.5 ± 0.45, p < 0.001). The levels of serum fructosamine and FBG were also significantly higher in patients with MDD when all participants were stratified by gender. Age was found to be positively correlated with FBG, serum fructosamine and Cr (r = 0.203, p < 0.001; r = 0. 129, p = 0.025; r = 0. 129, p = 0.024), and negatively correlated with TP (r = -0. 114, p = 0.047) in patients with MDD. However, there were no correlations between age and FBG, serum fructosamine or Cr in the healthy controls. In a multivariate logistic regression analysis, increased serum fructosamine and FBG concentrations were positively associated with MDD independently of age and gender, after adjustment for age and potential confounding factors (OR = 6.313, CI95 %:2.953-13.393, p < 0.001; OR = 2.251, CI95 %: 1.464-3.462, p < 0.001). Conclusions.The study results suggest that increased serum fructosamine and FBG concentrations are associated with depressive conditions, which may influence glucose metabolism and impair glucose homeostasis in patients with MDD.

show abstract

“…[25][26][27] In addition, glucocorticoids induce peripheral insulin resistance. 27) Although the serum concentration of corticosterone increased after the infusion of olanzapine in the present study, no significant difference was noted among the olanzapine dose groups (Fig. 2C).…”

Section: Discussionmentioning

confidence: 99%

Mechanism Underlying Induction of Hyperglycemia in Rats by Single Administration of Olanzapine

Nagata

Nakajima

Ishiwata

et al. 2016

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Acute administration of olanzapine rapidly elevates blood glucose levels. However, the mechanism underlying the rapid development of hyperglycemia with the administration of olanzapine remains unclear. The aim of the present study was to clarify the mechanism underlying olanzapine-induced acute hyperglycemia. Male Wistar rats received an intravenous infusion of saline (control) or olanzapine 2.5, 5, or 10 mg/kg. Blood samples were obtained periodically after olanzapine infusion to determine serum concentrations of glucose, olanzapine, and several endogenous substances. In a separate experiment, rats received an intravenous injection of propranolol (2 mg/kg) 30 min before infusion of olanzapine (10 mg/kg). The intravenous infusion of olanzapine induced dose-dependent increases in the serum concentrations of glucose, epinephrine, and insulin. Pretreatment with propranolol suppressed olanzapine-induced elevations in the serum concentration of glucose, but did not affect the serum concentration of olanzapine or olanzapine-induced increase in the serum concentration of epinephrine. Although the serum concentration of corticosterone increased after administration of olanzapine, no significant differences were observed among the olanzapine dose groups. Furthermore, administration of olanzapine did not affect the serum concentration of glucagon or histamine. We developed a pharmacokinetic-pharmacodynamic model assuming that the olanzapine-induced secretion of epinephrine leads to elevated serum glucose concentrations. This model appeared to satisfactorily characterize olanzapine-induced hyperglycemia. In conclusion, a single intravenous dose of olanzapine dosedependently increased the serum concentration of glucose in rats, and epinephrine plays a role in olanzapineinduced acute hyperglycemia.

show abstract

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

Cited by 177 publications

References 115 publications

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

HPA axis and vagus nervous function are involved in impaired insulin secretion of MSG-obese rats

The relationship between major depressive disorders and glucose parameters: A cross-sectional study in Chinese population

Mechanism Underlying Induction of Hyperglycemia in Rats by Single Administration of Olanzapine

Contact Info

Product

Resources

About