Alterations of epinephrine-induced gluconeogenesis in aging

Kim, Kyung‐Tae; Cho, Sung Chun; Cova, Anthony; Jang, Ik Soon; Park, Sang Chul

doi:10.3858/emm.2009.41.5.037

Cited by 8 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, our data agree with reports of age-related alterations in G protein-coupled receptor kinases (GRKs) and β-arrestin expression and activity in liver, vascular smooth muscle and myocardial cells from F344 rats [Kim et al, 2009; Schutzer et al, 2005; Dobson et al, 2003]. Since GRKs, particularly, GRK-2, and β-arrestin are required for β 2 -AR desensitization through internalization and degradation, our observed increase in β-AR signaling despite increased SNA could also be explained by a deficiency of old splenocytes to internalize β-AR in response to higher NE concentrations.…”

Section: Discussionsupporting

confidence: 92%

Chronically lowering sympathetic activity protects sympathetic nerves in spleens from aging F344 rats

Perez

Kozic

Molinaro

et al. 2012

Journal of Neuroimmunology

View full text Add to dashboard Cite

In the present study, we investigated how increased sympathetic tone during middle-age affects the splenic sympathetic neurotransmission. Fifteen-month-old F344 rats received rilmenidine (0, 0.5 or 1.5 mg/kg/day, i.p. for 90 days) to lower sympathetic tone. Controls for age were untreated 3 or 18M rats. We report that rilmenidine (1) reduced plasma and splenic norepinephrine concentrations and splenic norepinephrine turnover, and partially reversed the sympathetic nerve loss; and (2) increased β-adrenergic receptor (β-AR) density and β-AR-stimulated cAMP production. Collectively, these findings suggest a protective effect of lowering sympathetic tone on sympathetic nerve integrity, and enhanced sympathetic neurotransmission in secondary immune organs.

show abstract

Section: Discussionsupporting

confidence: 92%

Chronically lowering sympathetic activity protects sympathetic nerves in spleens from aging F344 rats

Perez

Kozic

Molinaro

et al. 2012

Journal of Neuroimmunology

View full text Add to dashboard Cite

show abstract

“…[19][20][21] Our results showed that the serum concentration of epinephrine increased in a dosedependent manner after the administration of olanzapine (Fig. 3B).…”

Section: Discussionmentioning

confidence: 61%

“…Serum concentrations of immunoreactive insulin and glucagon were 1,OLZ , the serum concentration of olanzapine in the central compartment; C 2,OLZ , the serum concentration of olanzapine in the peripheral compartment; V 1 , the distribution volume of olanzapine in the central compartment; k 12 , the first order transfer rate constant for a drug moving from the central to the peripheral compartment; k 21 , the first order transfer rate constant for a drug moving from the peripheral to the central compartment; V max,OLZ , the maximum velocity of the elimination of olanzapine; K m,OLZ , the Michaelis constant for the elimination of olanzapine; C Epi , the serum concentration of epinephrine; k in,Epi , the zero order constant for epinephrine input; C Epi(0) , the serum concentration of epinephrine at baseline; K S,Epi , the proportionality constant for the stimulation of epinephrine input by olanzapine; C Glu , the serum concentration of glucose; k in,Glu , the zero order constant for glucose input; C Glu(0) , the serum concentration of glucose at baseline; E max,Glu the maximum effect for the stimulation of glucose input by epinephrine; EC 50,Glu , the epinephrine concentration corresponding to 50% of the maximum effect for the stimulation of glucose input by epinephrine.…”

Section: Methodsmentioning

confidence: 99%

“…where 21 , V max,OLZ , and K m,OLZ represent the serum concentration of olanzapine in the central compartment, the serum concentration of olanzapine in the peripheral compartment, the distribution volume of olanzapine in the central compartment, first order transfer rate constant for a drug moving from the central to the peripheral compartment, first order transfer rate constant for a drug moving from the peripheral to the central compartment, the maximum velocity of the elimination of olanzapine, and the Michaelis constant for the elimination of olanzapine. The indirect response model proposed by Jusko et al 15,16) was applied to account for the olanzapine-induced increase in epinephrine secretion and subsequent increase in serum glucose.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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

“…Indeed, GRK and β‐arrestin1 are altered in congestive heart failure (Vinge et al ., ), and GRK2/3 in the failing human heart (Ungerer et al ., ). Studies in other tissues support age‐dependent shifts in GRK expression: GRK2 and 6 (and β‐arrestin‐2) are suppressed with age in the human brain (Grange‐Midroit et al ., ); and age switches the liver isoform profile from GRK2 to GRK3 and down‐regulates β‐arrestin (Kim et al ., ). In contrast, in diabetic mice, hyperinsulinaemia up‐regulates GRK (and down‐regulates β‐arrestin2) in vascular smooth muscle, inhibiting activation of the Akt/eNOS pathway involved in cytoprotection in other cell types (Taguchi et al ., ).…”

Section: Sarcolemmal Makeup and Cardioprotective Signallingmentioning

confidence: 97%

Sarcolemmal dependence of cardiac protection and stress‐resistance: roles in aged or diseased hearts

Hoe

May

Headrick

et al. 2016

British J Pharmacology

View full text Add to dashboard Cite

Disruption of the sarcolemmal membrane is a defining feature of oncotic death in cardiac ischaemia-reperfusion (I-R), and its molecular makeup not only fundamentally governs this process but also affects multiple determinants of both myocardial I-R injury and responsiveness to cardioprotective stimuli. Beyond the influences of membrane lipids on the cytoprotective (and death) receptors intimately embedded within this bilayer, myocardial ionic homeostasis, substrate metabolism, intercellular communication and electrical conduction are all sensitive to sarcolemmal makeup, and critical to outcomes from I-R. As will be outlined in this review, these crucial sarcolemmal dependencies may underlie not only the negative effects of age and common co-morbidities on myocardial ischaemic tolerance but also the on-going challenge of implementing efficacious cardioprotection in patients suffering accidental or surgically induced I-R. We review evidence for the involvement of sarcolemmal makeup changes in the impairment of stress-resistance and cardioprotection observed with ageing and highly prevalent co-morbid conditions including diabetes and hypercholesterolaemia. A greater understanding of membrane changes with age/disease, and the inter-dependences of ischaemic tolerance and cardioprotection on sarcolemmal makeup, can facilitate the development of strategies to preserve membrane integrity and cell viability, and advance the challenging goal of implementing efficacious 'cardioprotection' in clinically relevant patient cohorts. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.

show abstract

Alterations of epinephrine-induced gluconeogenesis in aging

Cited by 8 publications

References 30 publications

Chronically lowering sympathetic activity protects sympathetic nerves in spleens from aging F344 rats

Chronically lowering sympathetic activity protects sympathetic nerves in spleens from aging F344 rats

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

Sarcolemmal dependence of cardiac protection and stress‐resistance: roles in aged or diseased hearts

Contact Info

Product

Resources

About