Change of insulin action with aging in conscious rats determined by euglycemic clamp

Nishimura, Haruo; Kuzuya, Hideshi; Okamoto, Motozumi; Yoshimasa, Yasunao; Yamada, Kotaro; Ida, Takanori; Kakehi, Takako; Imura, Hiroo

doi:10.1152/ajpendo.1988.254.1.e92

Cited by 59 publications

(68 citation statements)

References 14 publications

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“…Ageing is associated with fat mass accretion (Nishimura et al 1988) and long-term changes in circulating adipokines could modulate insulin sensitivity. High levels of adiponectin have been associated with increased insulin sensitivity and, in situations of insulin resistance a low concentration of adiponectin has been observed (Chandran et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Aged Wistar rats present a lower glucose disposal rate during euglycemic-hyperinsulinemic clamp than mature young rats, without changes in fasting plasma glucose and insulin concentrations (Nishimura et al 1988, Escrivá et al 1997, demonstrating a state of insulin resistance. However, this decrease in insulin sensitivity, far from being homogeneous, is tissue specific.…”

Section: Introductionmentioning

confidence: 94%

“…Ageing is associated with a moderate decrease in peripheral insulin sensitivity in humans (De Fronzo 1981, Fink et al 1983, Rowe et al 1983) and rodents (Goodman et al 1983, Narimiya et al 1984, Nishimura et al 1988, Escrivá et al 1997. It is also associated with changes in body composition, especially in adipose tissue, making it difficult to evaluate the role of ageing by itself in the impairment of insulin action.…”

Section: Introductionmentioning

confidence: 99%

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Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity

Escrivá

Gavete

Fermín

et al. 2007

Journal of Endocrinology

117

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Insulin resistance develops with ageing in humans and rodents. Here, we have studied the evolution of insulin sensitivity with ageing trying to discriminate the role of adiposity from that of ageing in this process. We performed oral glucose tolerance tests and determined overall and tissue-specific glucose utilization under euglycemic-hyperinsulinemic conditions in 3-, 8-, and 24-month-old rats fed ad libitum, and in 8-and 24-month-old rats after 3 months of calorie restriction. Body composition and adipocytederived cytokines such as leptin, resistin, and adiponectin were analyzed. Overall insulin sensitivity decreases with ageing. Calorie restriction improves global insulin sensitivity in 8-but not in 24-month-old rats. Insulin-stimulated glucose utilization in adipose tissues decreases in 8 months, while in oxidative muscles it reaches significance only in older rats. Calorie restriction restores adipose tissue insulin sensitivity only in 8-month-old rats and no changes are observed in muscles of 24-month-old rats. Resistin and leptin increase with ageing. Food restriction lowers resistin and increases adiponectin in 8-month-old rats and decreases leptin in both ages. Visceral and total fat increase with ageing and decrease after calorie restriction. We conclude that accretion of visceral fat plays a key role in the development of insulin resistance after sexual maturity, which is reversible by calorie restriction. With aging, accumulation of retroperitoneal and total body fat leads to impaired muscle glucose uptake and to a state of insulin resistance that is difficult to reverse.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity

Escrivá

Gavete

Fermín

et al. 2007

Journal of Endocrinology

117

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“…Aged Wistar rats are characterized by fasting normoglycemia and normoinsulinemia and show overall insulin resistance as assessed by the euglycemic-hyperinsulinemic clamp technique (Nishimura et al 1988, Escrivá et al 1997.…”

Section: Introductionmentioning

confidence: 99%

Differential gene expression of insulin receptor isoforms A and B and insulin receptor substrates 1, 2 and 3 in rat tissues: modulation by aging and differentiation in rat adipose tissue

Serrano

Villar²,

Martı́nez

et al. 2005

Journal of Molecular Endocrinology

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The insulin receptor (IR) occurs as two alternatively spliced isoforms, IR-A (exon 11−) and IR-B (exon 11+), which exhibit functional differences and are expressed in a tissue-specific manner. The IR substrate (IRS) proteins 1, 2 and 3 also differ in function and tissue distribution. Here we show the differential gene expression of IRs and IRSs in several rat target tissues of insulin action. IR-B is significantly higher than IR-A in epididymal white adipose tissue and adipogenesis induces a shift in the alternatively spliced species of IR from the A to the B isoform. Moreover, since aging in the rat is associated with the development of insulin resistance we looked for alterations of expression of these proteins in adipocytes from old rats. Our results reveal that there is a specific decrease in the expression of the IR-B isoform, as well as both mRNA and protein levels of IR, IRS-1 and IRS-3 being significantly decreased, in epididymal adipose tissue from old compared with adult rats. It is concluded that the down-regulation of early components of the insulin transduction pathway in a primary insulin target tissue could be related to the insulin resistance of aging.

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“…Old Wistar rats are characterized by peripheral insulin resistance without overt alterations in glucose homeostasis and a moderate increase in adiposity without a considerable increment in the obesity Lee index [7,14,15]. These rats also show increased serum leptin concentrations during ageing, suggesting that they are leptin resistant [7].…”

mentioning

confidence: 99%

Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats

et al. 2002

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Aims/hypothesis. Ageing is associated with insulin and leptin resistance in mammals. These alterations might be caused by the increased adiposity associated with ageing, by ageing alone or both. We studied whether leptin resistance occurs at the central level in the Wistar rat and we aimed to discriminate between the effects of ageing from those of the increased adiposity associated with ageing. Methods. Leptin was infused intracerebroventricularly at a constant rate in young adult, old and old Wistar rats fasted for 3 months, using osmotic pumps. The effects on body weight, daily food intake, Lee index, adiposity and serum leptin values were analysed. The effect of food restriction on the expression of the long form of leptin receptor in the hypothalamus was also studied. Results. Leptin decreased daily food intake and body weight in young and old Wistar rats. With a dose of 10 µg/day similar responses were obtained in young and old rats but with a dose of 0.2 µg/day, only young rats showed decreases in these parameters. Foodrestriction in old rats lowered adiposity and serum leptin to values close to those of young rats, recovered responsiveness to i.c.v. administration of leptin at the dose of 0.2 µg/day and increased leptin receptor expression in the hypothalamus. Conclusion/interpretation. Our data show that old Wistar rats have a decreased response to leptin at the central level. Food-restriction recovers leptin responsiveness and increases leptin receptor in the hypothalamus suggesting that adiposity plays a key role in the development of leptin resistance associated with ageing. [Diabetologia (2002[Diabetologia ( ) 45:997-1003 Keywords Leptin, leptin-resistance, food-restriction, ageing, Wistar rat.

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Change of insulin action with aging in conscious rats determined by euglycemic clamp

Cited by 59 publications

References 14 publications

Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity

Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity

Differential gene expression of insulin receptor isoforms A and B and insulin receptor substrates 1, 2 and 3 in rat tissues: modulation by aging and differentiation in rat adipose tissue

Long-term food restriction prevents ageing-associated central leptin resistance in wistar rats

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