Effects of caloric restriction on SIRT1 expression and apoptosis of islet beta cells in type 2 diabetic rats

Deng, Xiaheng; Cheng, Jinquan; Zhang, Yunping; Li, Ningxu; Chen, Lulu

doi:10.1007/s00592-009-0159-7

Cited by 22 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SIRT1 has been associated with reduced apoptotic nuclear DNA degradation in islet beta cells [70] and with the prevention of membrane PS externalization in neurons [13, 39] and in lymphoblastoid cell lines [71]. In our model of ECs during elevated D-glucose exposure, we have specifically identified the ability of SIRT1 to prevent early apoptotic membrane PS externalization and subsequent nuclear DNA degradation.…”

Section: Discussionmentioning

confidence: 99%

Early Apoptotic Vascular Signaling is Determined by Sirt1 Through Nuclear Shuttling, Forkhead Trafficking, Bad, and Mitochondrial Caspase Activation

Hou¹,

Chong²,

Shang³

et al. 2010

CNR

120

View full text Add to dashboard Cite

Complications of diabetes mellitus (DM) weigh heavily upon the endothelium that ultimately affect multiple organ systems. These concerns call for innovative treatment strategies that employ molecular pathways responsible for cell survival and longevity. Here we show in a clinically relevant model of DM with elevated D-glucose that endothelial cell (EC) SIRT1 is vital for the prevention of early membrane apoptotic phosphatidylserine externalization and subsequent DNA degradation supported by studies with modulation of SIRT1 activity and gene knockdown of SIRT1. Furthermore, during elevated D-glucose exposure, we show that SIRT1 is sequestered in the cytoplasm of ECs, but specific activation of SIRT1 shuttles the protein to the nucleus to allow for cytoprotection. The ability of SIRT1 to avert apoptosis employs the activation of protein kinase B (Akt1), the posttranslational phosphorylation of the forkhead member FoxO3a, the blocked trafficking of FoxO3a to the nucleus, and the inhibition of FoxO3a to initiate a "pro-apoptotic" program as shown by complimentary gene knockdown studies of FoxO3a. Vascular apoptotic oversight by SIRT1 extends to the direct modulation of mitochondrial membrane permeability, cytochrome c release, Bad activation, and caspase 1 and 3 activation, since inhibition of SIRT1 activity and gene knockdown of SIRT1 significantly accentuate cascade progression while SIRT1 activation abrogates these apoptotic elements. Our work identifies vascular SIRT1 and its control over early apoptotic membrane signaling, Akt1 activation, post-translational modification and trafficking of FoxO3a, mitochondrial permeability, Bad activation, and rapid caspase induction as new avenues for the treatment of vascular complications during DM.

show abstract

Section: Discussionmentioning

confidence: 99%

Early Apoptotic Vascular Signaling is Determined by Sirt1 Through Nuclear Shuttling, Forkhead Trafficking, Bad, and Mitochondrial Caspase Activation

Hou¹,

Chong²,

Shang³

et al. 2010

CNR

120

View full text Add to dashboard Cite

show abstract

“…These effects are mediated by a wide spectrum of biochemical and cellular adaptations, including redox homeostasis, mitochondrial function [80] , inflamma tion [81,82] , apoptosis [83] , and autophagy [84] . Oxidative stress plays an important role in the pathogenesis of coronary artery disease by mediating expression of inflammatory genes and eliciting oxidative modification of lipoprotein particles [85,86] .…”

Section: Signal Transduction Mechanism Involved In Crmentioning

confidence: 99%

Caloric restriction and heart function: is there a sensible link?

Han

Ren

2010

Acta Pharmacol Sin

View full text Add to dashboard Cite

Calorie restriction (CR) is defined as a reduction in calorie intake below the usual ad libitum intake without malnutrition. In general, the daily caloric intake subjected to CR has been restricted to 50% to 70% of the average food intake in subjects eating ad libitum [1,2] . CR was first reported to retard aging and prolong median and maximal life span in the 1930s [3] . Over the last several decades, CR has been widely studied which exhibits an apparent beneficial impact on longevity, ageassociated diseases, and attenuation of functional decline, across a broad variety of species (including rats, mice, fish, flies, worms and yeast) [4,5] . Moreover, CR provides protection against a cadre of chronic diseases including diabetes mellitus, neurodegenerative diseases, autoimmune disorders [6][7][8] and cancer [9][10][11][12] . CR has been shown to alter a variety of physiological parameters especially reduced metabolic rate and oxidative damage, resulting in a decrease in the incidence of cardiovascular diseases [13] . In response to energy deficiency, experimental animals experience a drastic decrease in both fat mass and lean body mass. Muscle mass is overtly reduced, although the rate of loss of function and mass/body weight with the aging process is attenuated [9,[14][15][16] . Metabolic rate may decrease transiently although studies have indicated similar metabolic rate per kg lean body mass to that of ad libitum fed rodents in longterm CR protocol [17] . Body temperature, systolic and diastolic blood pressure all decrease [18,19] along with the reduced sympathetic activity [20] . CR-treated animals are more spontaneously active and display superior cognitive abilities compared to their ad libitum counterparts [21,22] .The most prominent mechanism that may be responsible for the beneficial health and physiological effects of CR are usually mediated through increased insulin sensitivity which results in reduced plasma glucose and insulin concentrations and improved glucose tolerance [23] ; reduced levels of oxidative stress (decreased oxidative damage to proteins, lipids and DNA) [24] , increased resistance to various types of stress including heat, oxidative and metabolic stress [25] as well as enhanced immune function [26] . Impact of CR on agingAn inverse relationship between calorie intake and lifespan has been revealed in mice, suggesting a key role for regulators of energy metabolism in the mechanism of CR. Accordingly, CR-induced metabolic reprogramming may be a key event in the mechanism of lifespan extension [27,28] . The age when CR is started, the severity of restriction, and strain or genetic background of animals determine the magnitude of life extension. The only mammals in which CR has clearly been shown ReviewCaloric restriction and heart function: is there a sensible link? Calorie restriction (CR) is defined as a reduction in calorie intake below the usual ad libitum intake without malnutrition. Ample of clinical and experimental evidence has demonstrated that CR is capable of retarding aging p...

show abstract

“…Sir2 levels are known to increase with nutrient deprivation, and in those cases caloric restriction did not extend the lifespan in Sir2/Sirt1-deficient Drosophila, yeast or mice. In mammals, Sirt1 expression and activity are regulated by nutrient availability, which modulates the adaptive response to caloric restriction [35]. More recently, dietary restriction has been used to reduce oxidative stress by SIRT3-mediated SOD2 activation [36].…”

Section: Discussionmentioning

confidence: 99%

Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice

Kanda

Hashiramoto

Shimoda

et al. 2015

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

Effects of caloric restriction on SIRT1 expression and apoptosis of islet beta cells in type 2 diabetic rats

Cited by 22 publications

References 31 publications

Early Apoptotic Vascular Signaling is Determined by Sirt1 Through Nuclear Shuttling, Forkhead Trafficking, Bad, and Mitochondrial Caspase Activation

Early Apoptotic Vascular Signaling is Determined by Sirt1 Through Nuclear Shuttling, Forkhead Trafficking, Bad, and Mitochondrial Caspase Activation

Caloric restriction and heart function: is there a sensible link?

Dietary restriction preserves the mass and function of pancreatic β cells via cell kinetic regulation and suppression of oxidative/ER stress in diabetic mice

Contact Info

Product

Resources

About