Article

Brain region-dependent effects of dexamethasone on counterregulatory responses to hypoglycemia in conscious rats.

Department of Medicine, Vanderbilt University School of Medicine, Nashville Veterans Affairs Medical Center, Nashville, TN 37232-6303, USA.
AJP Regulatory Integrative and Comparative Physiology (impact factor: 3.34). 03/2005; 288(2):R413-9. DOI:10.1152/ajpregu.00674.2003 pp.R413-9
Source: PubMed

ABSTRACT The aim of this study was to determine whether activation of central type II glucocorticoid receptors can blunt autonomic nervous system counterregulatory responses to subsequent hypoglycemia. Sixty conscious unrestrained Sprague-Dawley rats were studied during 2-day experiments. Day 1 consisted of either two episodes of clamped 2-h hyperinsulinemic (30 pmol x kg(-1) x min(-1)) hypoglycemia (2.8 +/- 0.1 mM; n = 12), hyperinsulinemic euglycemia (6.2 +/- 0.1 mM; n = 12), hyperinsulinemic euglycemia plus simultaneous lateral cerebroventricular infusion of saline (24 microl/h; n = 8), or hyperinsulinemic euglycemia plus either lateral cerebral ventricular infusion (n = 8; LV-DEX group), fourth cerebral ventricular (n = 10; 4V-DEX group), or peripheral (n = 10; P-DEX group) infusion of dexamethasone (5 microg/h), a specific type II glucocorticoid receptor analog. For all groups, day 2 consisted of a 2-h hyperinsulinemic (30 pmol x kg(-1) x min(-1)) or hypoglycemic (2.9 +/- 0.2 mM) clamp. The hypoglycemic group had blunted epinephrine, glucagon, and endogenous glucose production in response to subsequent hypoglycemia. Consequently, the glucose infusion rate to maintain the glucose levels was significantly greater in this group vs. all other groups. The LV-DEX group did not have blunted counterregulatory responses to subsequent hypoglycemia, but the P-DEX and 4V-DEX groups had significantly lower epinephrine and norepinephrine responses to hypoglycemia compared with all other groups. In summary, peripheral and fourth cerebral ventricular but not lateral cerebral ventricular infusion of dexamethasone led to significant blunting of autonomic counterregulatory responses to subsequent hypoglycemia. These data suggest that prior activation of type II glucocorticoid receptors within the hindbrain plays a major role in blunting autonomic nervous system counterregulatory responses to subsequent hypoglycemia in the conscious rat.

0 0
 · 
0 Bookmarks
 · 
21 Views
  • Source
    Article: Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake.
    Darleen A Sandoval, Didier Bagnol, Stephen C Woods, David A D'Alessio, Randy J Seeley
    [show abstract] [hide abstract]
    ABSTRACT: Glucagon-like peptide-1 (GLP-1) promotes glucose homeostasis through regulation of islet hormone secretion, as well as hepatic and gastric function. Because GLP-1 is also synthesized in the brain, where it regulates food intake, we hypothesized that the central GLP-1 system regulates glucose tolerance as well. We used glucose tolerance tests and hyperinsulinemic-euglycemic clamps to assess the role of the central GLP-1 system on glucose tolerance, insulin secretion, and hepatic and peripheral insulin sensitivity. Finally, in situ hybridization was used to examine colocalization of GLP-1 receptors with neuropeptide tyrosine and pro-opiomelanocortin neurons. We found that central, but not peripheral, administration of low doses of a GLP-1 receptor antagonist caused relative hyperglycemia during a glucose tolerance test, suggesting that activation of central GLP-1 receptors regulates key processes involved in the maintenance of glucose homeostasis. Central administration of GLP-1 augmented glucose-stimulated insulin secretion, and direct administration of GLP-1 into the arcuate, but not the paraventricular, nucleus of the hypothalamus reduced hepatic glucose production. Consistent with a role for GLP-1 receptors in the arcuate, GLP-1 receptor mRNA was found to be expressed in 68.1% of arcuate neurons that expressed pro-opiomelanocortin mRNA but was not significantly coexpressed with neuropeptide tyrosine. These data suggest that the arcuate GLP-1 receptors are a key component of the GLP-1 system for improving glucose homeostasis by regulating both insulin secretion and glucose production.
    Diabetes 06/2008; 57(8):2046-54. · 8.29 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

2-day experiments
 
2-h hyperinsulinemic
 
4V-DEX group
 
4V-DEX groups
 
central type II glucocorticoid receptors
 
conscious rat
 
conscious unrestrained Sprague-Dawley rats
 
endogenous glucose production
 
fourth cerebral ventricular
 
glucose infusion rate
 
hyperinsulinemic euglycemia
 
hypoglycemic group
 
lateral cerebral ventricular infusion
 
LV-DEX group
 
P-DEX group
 
prior activation
 
significant blunting
 
simultaneous lateral cerebroventricular infusion
 
specific type II glucocorticoid receptor analog
 
type II glucocorticoid receptors