Biomedical subjects

Dominique Meynial-Denis

Publications and source records attributed to Dominique Meynial-Denis.

6 recordsLinked to original sources

PubMed2005

Does acute glutamine depletion enhance the response of glutamine synthesis to fasting in muscle in adult and old rats?

BACKGROUND AND AIMS: In earlier studies, skeletal muscle glutamine synthetase (GS) activity was shown to be enhanced by fasting and glucocorticoids, and inhibited by exogenous glutamine (Gln) supplementation. The current study was designed to determine whether phenylbutyrate (PhiB), a Gln-chelating agent in humans, (1) could trap Gln and produce a decline in plasma Gln in rats, as it does in humans, and (2) if so, whether (Phi)B would further enhance the response of muscle GS activity to fasting in rats. METHODS: Adult (6-8 months) and aged (20-21 months) rats were fasted for 5 days and received two doses of 0.5 g(Phi)Bby orogastric route at times 0 and 4 h, and were then sacrificed at 5.5 h. Plasma Gln was measured by enzymatic methods, other amino acids were quantified by amino acid analysis. GS activity was measured in soleus (SO) and tibialis anterior (TA) muscles. RESULTS: (Phi)B treatment was associated with: (1) a 20% decline in plasma Gln concentration from 572+/-54 to 424+/-34 micromol/L (P<0.05) and from 476+/-49 to 360+/-80 micromol/L (P<0.05) in fasted adult and old rats, respectively; and (2) a preservation of GS up-regulation by fasting in TA and SO muscles in both adult and aged rats, with TA muscle GS activities of 198+/-65 vs. 203+/-68 ((Phi)B-treated vs. vehicle-treated, NS), and 244+/-81 vs. 274+/-59 (NS) nmol/h/mg protein in adult and aged rats, respectively. CONCLUSION: These data suggest that: (1) large doses of (Phi)B deplete plasma Gln in fasted rats, regardless of age, (2) Gln depletion induced by Phi)B does not alter GS activity.

Age Factors↗

PubMed2005

Insulin-dependent glycogen synthesis is delayed in onset in the skeletal muscle of food-deprived aged rats.

Insulin resistance with aging may be responsible for impaired glycogen synthesis in the skeletal muscle of aged rats and contribute to the well-known decreased ability to respond to stress with aging. For this reason, to assess the ability of the skeletal muscle to utilize glucose for glycogen synthesis during aging, the time course of glycogen synthesis was continuously monitored by 13C nuclear magnetic resonance for 2 h in isolated [13C] glucose-perfused gastrocnemius-plantaris muscles of 5-day food-deprived adult (6-8 months; n=10) or 5-day food-deprived aged (22 months; n=8) rats. [13C] glucose (10 mmol/L) perfusion was carried out in the presence or absence of an excess of insulin (1 micromol/L). Food deprivation only decreased glycogen level in adult rats (8.9+/-2.4 micromol/g in adults vs. 35.6+/-2.4 micromol/g in aged rats; P<.05). In the presence of an excess of insulin, muscle glycogen synthesis was stimulated in both adult and aged muscles, but the onset was delayed with aging (40 min later). In conclusion, this study highlights the important role of glycogen depletion in stimulating glycogen synthesis in muscles. Consequently, the absence of glycogen depletion in response to starvation in aged rats may be the origin of the delay in insulin-stimulated glycogen synthesis in the skeletal muscle. Glycogen synthesis clearly was not impaired with aging.

Aging↗

PubMed2002

The LOU/c/jall rat as an animal model of healthy aging?

We propose the LOU/c/jall rat as a possible model for research into aging. Physiological and behavioral data have been collected over the past 5 years, using lifelong and cross-sectional studies. The median life span of the rats was 29 months in males and 33-34 months in females. A low level of body fat throughout life was observed in both sexes. Basic phenomena of aging such as body weight loss, decrease in caloric intake, and dramatic drop in protein selection were noted from the age of 18 months in males and 28 months in females. A decline in muscle mass, depending on the sex and the type of muscle, was seen. These data allowed us to demonstrate physiological aging in male and female LOU/c/jall rats. The most interesting characteristics of this strain of rat for aging studies are longevity, and the absence of obesity and of severe pathologies. Further studies are required in order to confirm this last point.

Adaptation, Physiological↗

PubMed2002

Do sex steroids regulate glutamine synthesis with age?

Glutamine synthetase, a key enzyme in the production of glutamine, is known to be induced by glucocorticoids and preserved in skeletal muscle during aging, but the effect of other steroids, such as sex steroids (progesterone, estradiol), is unknown in vivo. The aim of this study was to determine whether progesterone or estradiol plays a role in the regulation of glutamine synthetase (GS) with aging. The effects of glucocorticoids and sex steroids on muscle GS activity and mRNA expression were measured in adult (6-8 mo; n = 7 in each group) and aged (26 mo; n = 10 in each group) female Wistar rats after adrenalectomy (ADX), ovariectomy (OV), or both (ADXOV) and were compared with those in sham-operated (Sham) control rats. In tibialis anterior muscle, ADX noticeably decreased both GS activity and expression irrespective of age (50-60%; P < 0.05), whereas OV had no effect at either age. Progesterone and estradiol replacement had no effect on the recovery of muscle GS response in either ADX or OV rats, regardless of age. In contrast, heart GS activity was decreased by ADX in aged animals only. These results suggest that the reproductive endocrine status of female rats does not affect muscle GS activity either in muscle or in heart, in young or aged animals, and that the heart GS response to steroids may be differently regulated in aged rats.

Adrenalectomy↗

PubMedDate not supplied

Alterations in glutamine synthetase activity in rat skeletal muscle are associated with advanced age.

OBJECTIVE: Glutamine synthetase (GS), a key enzyme in the production of glutamine, is preserved in skeletal muscle during early aging (<24 mo). Because the effects of advanced age on GS are unknown, we investigated the effect of advanced age (>24 mo) on GS activity in skeletal muscle. We hypothesized that advanced age would enhance muscle GS activity. METHODS: Muscle GS activities were assessed in adult (8 mo), mature adult (15 mo), aged (20-22 mo), advanced age (25-27 mo), or very advanced age (29-32 mo) female Wistar rats. Male Wistar (6-27 mo) were used to investigate the effect of gender on this activity. RESULTS: Glutamine synthetase activity remained low and unaltered in rats from 8 to 22 mo of age, as previously demonstrated. In contrast, GS activity was high ( approximately 75% of individual values were higher than the low value mean) in 25-mo to 27-mo-old rats. In very-old-aged rats (29-32 mo), approximately 55% of GS activity data points exhibited low values. Changes in GS protein content paralleled those in GS activities. In male rats, GS activity was also high ( approximately 80% of individual values were higher than the mean value of 6-mo to 19-mo-old rats) at the upper limit of life expectancy (27 mo). CONCLUSION: There is enhanced GS activity in old female and male rats suggesting a greater need for glutamine. In some very old rats, low GS activity may be associated with longevity or reflect a limitation in glutamine production due to extremely advanced age per se.

Adenosine Triphosphate↗

PubMedDate not supplied

Does glutamine supplementation decrease the response of muscle glutamine synthesis to fasting in muscle in adult and very old rats?

BACKGROUND: Glutamine synthetase (GS), a key enzyme in the production of glutamine, is preserved in rat skeletal muscle during aging but is increased with advanced age in vivo. The aim of this study was to determine whether glutamine supplementation affects up-regulation of GS by fasting in vivo in adult and very old female rats. METHODS: Muscle GS activities were assessed in 5-day-fasted female Wistar adult (6 months) and very old (27 months) rats refed and supplemented with glutamine or other amino acids (alanine or glycine). Fed rats were used to investigate the possible effect of glutamine supplementation in the fed state. RESULTS: After 5 days' fasting, the up-regulated GS activity was decreased whatever the type of amino acid supplementation (glutamine, alanine, and glycine) in adults, whereas it was only decreased by glutamine supplementation in very old rats). In the fed state, no effect of glutamine supplementation was observed even if GS activity remained up-regulated whatever the age and the period of supplementation. CONCLUSIONS: These results confirm that glutamine has a specific role in very old rats. The up-regulated GS activity was decreased by an exogenous supply of glutamine only if intramuscular glutamine was depleted; this was confirmed by studies in the fed state. The up-regulated GS activity in both fed and fasted rats may be associated with increased glutamine requirements in the whole body.

Aging↗