Impaired insulin release in aging rats: Metabolic and ionic events

Castro, Mario; Pedrosa, Diego França; Osuna, Jesús

doi:10.1007/bf01952596

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…Functional Alterations in CaM-Dependent Enzymes During Aging. While previous measurements have not identified age-related alterations in the function of CaM, reported reductions in the activity of the PM-Ca-ATPase and CaMdependent protein kinase II isolated from the brains of older animals could be the result of decreased expression levels or oxidative modifications involving CaM (56)(57)(58)(59)(60). Similar reductions in the transport activity of the PM-Ca-ATPase in aged erythrocytes are reversed upon purification of the erythrocyte ghosts and addition of exogenous CaM (61,62), suggesting that CaM itself may be a principal target of ROS under conditions involving oxidative stress.…”

Section: Discussionmentioning

confidence: 91%

Progressive Decline in the Ability of Calmodulin Isolated from Aged Brain To Activate the Plasma Membrane Ca-ATPase

et al. 1998

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To identify possible relationships between the loss of calcium homeostasis in brain associated with aging and alterations in the function of key calcium regulatory proteins, we have purified calmodulin (CaM) from the brains of Fischer 344 rats of different ages and have assessed age-related alterations in (i) the secondary and tertiary structure of CaM and (ii) the ability of CaM to activate one of its target proteins, the plasma membrane (PM) Ca-ATPase. There is a progressive, age-dependent reduction in the ability of CaM to activate the PM-Ca-ATPase, which correlates with the oxidative modification of multiple methionines to their corresponding methionine sulfoxides. No other detectable age-related posttranslational modifications occur in the primary sequence of CaM, suggesting that the reduced ability of CaM to activate the PM-Ca-ATPase is the result of methionine oxidation. Corresponding age-related changes in the secondary and tertiary structure of CaM occur, resulting in alterations in the relative mobility of CaM on polyacrylamide gels, differences in the intrinsic fluorescence intensity and solvent accessibility of Tyr99 and Tyr138, and a reduction in the average alpha-helical content of CaM at 20 degreesC. Shifts in the calcium- and CaM-dependent activation of the PM-Ca-ATPase are observed for CaM isolated from senescent brain, which respectively requires larger concentrations of either calcium or CaM to activate the PM-Ca-ATPase. The observation that the oxidative modification of CaM during normal biological aging results in a reduced calcium sensitivity of the PM-Ca-ATPase, a lower affinity between CaM and the PM-Ca-ATPase, and the reduction in the maximal velocity of the PM-Ca-ATPase is consistent with earlier results that indicate the calcium handling capacity of a range of tissues including brain, heart, and erythrocytes isolated from aged animals declines, resulting in both longer calcium transients and elevated basal levels of intracellular calcium. Thus, the oxidative modification of selected methionines in CaM may explain aspects of the loss of calcium homeostasis associated with the aging process.

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Section: Discussionmentioning

confidence: 91%

Progressive Decline in the Ability of Calmodulin Isolated from Aged Brain To Activate the Plasma Membrane Ca-ATPase

et al. 1998

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“…Investigations by Elahi et al (79,Reaven and Reaven (76), Sartin et al (77), and Castro (17), have demonstrated attenuated glucose oxidation concomitant with diminished insulin secretion in islets isolated from older versus younger rats. In contrast, Ammon et al (78) reported no differences in glucose utilization nor in NADPH production in islets from old rats as compared to islets from younger animals.…”

Section: Glucose Oxidation Insulin Secretion and Agingmentioning

confidence: 96%

Aging and Insulin Secretion

Coordt¹,

Ruhe²,

McDonald³

1995

Experimental Biology and Medicine

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Aging in mammals has often been associated with decreased insulin secretion and a subsequent deterioration in the ability to maintain glucose homeostasis. However, recent studies have demonstrated that factors such as disease, obesity, and physical activity more closely reflect diminished insulin secretion rather than aging per se. Thus, the purpose of this article is to review recent studies of how biological aging, i.e. the process independent of disease states such as type II diabetes, may affect insulin secretion. To this end, this review will address the impact of aging on insulin secretion in terms of in vivo and in vitro assessment, as well as possible age-related alterations in the hormonal and neural regulation of insulin secretion. Finally, this review describes some evidence that alterations in the functional heterogeneity of the beta-cell population may represent a means by which the endocrine pancreas is able to maintain appropriate insulin secretion during senescence.

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“…These phenomena may be explained by the reduced capacity of response of pancreatic -cells and by the insulin resistance occurring in aging (Castro et al 1993, Carvalho et al 1996, Rocha et al 2003, 2004. However, the similarity of insulin content and secretion by LGs in the aging and young groups may suggest mechanisms to preserve the levels offered to the LGs and ocular surface, and supports the theory that this hormone is a key element for LGs and ocular surface maintenance (Hann et al 1991).…”

Section: Figurementioning

confidence: 89%

“…Metabolic alterations involving early elements of the signaling cascades may be related to insulin reduction or resistance and consequent organ dysfunctions in old rats (Castro et al 1993, Perfetti et al 1995, Paez-Espinosa et al 1999, Rocha et al 2004). One of the major consequences of insulin resistance, as observed in the elderly, is chronic hyperglycemia and oxidative stress leading to the formation of AGEs, obtained from chemical reaction of carbohydrates with proteins (Pongor et al 1984, Singh et al 2001, Evans et al 2002.…”

Section: Introductionmentioning

confidence: 99%

“…It is present in the tear film, and insulin receptors (IRs) have been demonstrated in LGs (Hann et al 1991, Rocha et al 2000. In rats, insulin secretion from pancreatic islet cells (Castro et al 1993, Perfetti et al 1995 and the secretory response of LGs are impaired by aging (Draper et al 2003). It is unknown whether insulin secretion is reduced in aging LGs following the secretory dysfunctions observed in these tissues.…”

Section: Introductionmentioning

confidence: 99%

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Nuclear factor-κB and advanced glycation end-products expression in lacrimal glands of aging rats

Alves

Cunha

Calegari

et al. 2005

Journal of Endocrinology

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Advanced glycation end products (AGEs) increase with aging and induce signaling alterations that lead to inflammation and dysfunction in several tissues. Aging reduces function and insulin signaling in lacrimal glands (LGs). To evaluate whether AGE signaling and insulin secretion inLGs are altered in aging, 24-and 2-month-old male Wistar rats were compared. Immunohistochemistry with confocal microscopy was used to evaluate AGE, AGE receptor (RAGE) and nuclear factor-B (NF-B) expression in LGs. Basal tear secretion volume, insulin, interleukin-1 (IL-1 ) and tumor necrosis factor-(TNF-) levels in tears and LGs and peroxidase activity in LG tissue were measured. Insulin secretion from isolatedLGs and pancreatic -cells was compared in the supernatant of aging and control rats in vitro by RIA after stimulation with 2·8-16·7 mM glucose, carbachol and KCl. AGE, RAGE and NF-B expression was higher inLGs of aging compared with young rats. Basal tear secretion and peroxidase activity were significantly lower in the aging group (P=0·016 for both assays). IL-1 and TNF-levels were higher in tears of aging rats compared with young rats (P=0·007 and 0·05 respectively); however, even though aging rats were insulin-resistant (as confirmed by the insulin-tolerance test), the insulin levels in the tear film of aging and control rats were similar in vivo and in vitro. The higher expression of AGEs, RAGE and NF-B in LGs of aging rats is accompanied by systemic insulin resistance and may be involved in LG and tear film alterations but does not affect insulin secretion in the tear film. These observations indicate that metabolic events may be related to LG and tear film dysfunctions in aging.

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Impaired insulin release in aging rats: Metabolic and ionic events

Cited by 8 publications

References 17 publications

Progressive Decline in the Ability of Calmodulin Isolated from Aged Brain To Activate the Plasma Membrane Ca-ATPase

Progressive Decline in the Ability of Calmodulin Isolated from Aged Brain To Activate the Plasma Membrane Ca-ATPase

Aging and Insulin Secretion

Nuclear factor-κB and advanced glycation end-products expression in lacrimal glands of aging rats

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