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Biomedical subjects

D A Podolin

Publications and source records attributed to D A Podolin.

8 recordsLinked to original sources

Hormonal regulation of hepatic gluconeogenesis: influence of age and training.

The contributions of three major gluconeogenic regulators, glucagon (10(-7) M), alpha-adrenergic agonist phenylephrine (10(-5) M), and beta-agonist isoproterenol (10(-5) M) to hepatic glucose synthesis in liver slices from Fischer 344 rats were examined in relation to age and endurance training. Young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats (n = 66) were divided into trained or sedentary groups. Trained animals were run 10 wk on a treadmill at 75% of maximal capacity, 1 h/day, 5 days/wk. Animals were killed at rest, and sections of liver were removed and sliced in a tissue microtome. Slices were incubated in L-[U-14C]lactic acid, Ringer solution, and one of the aforementioned gluconeogenic regulators. Rates of lactate incorporation into glucose and glycogen were significantly greater in young compared with old animals for all three regulators in both trained and untrained animals. Training elicited a 35, 52, and 63% improvement in lactate incorporation into glucose compared with untrained when the livers of young (16.9 +/- 1.2 vs. 10.9 +/- 1.1 mumol.g protein-1.min-1), middle-aged (12.8 +/- 1.3 vs. 6.1 +/- 1.2 mumol.g protein-1.min-1), and old (11.2 +/- 1.1 vs. 4.1 +/- 0.6 mumol.g protein-1.min-1) animals, respectively, were incubated in glucagon. Rates with phenylephrine followed a similar pattern to that with glucagon across age and training, but absolute rates were significantly lower. No training effect in gluconeogenic rate was found when liver was incubated in the presence of isoproterenol. It is concluded that the gluconeogenic capacity of liver declines with age regardless of the gluconeogenic regulator and that training was able to partially offset age-related declines in glucagon-stimulated and alpha-receptor-mediated gluconeogenesis.

Aging

Effects of age and endurance training on beta-adrenergic receptor characteristics in Fischer 344 rats.

The purpose of this investigation was to examine changes in beta-adrenergic receptor characteristics in various tissues with age and endurance training. Forty-eight young (6 months), middle-aged (15 months), and old (25 months) male Fischer 344 rats were assigned to either a trained or sedentary running group. Animals were endurance trained by 10 weeks of treadmill running at 75% maximal capacity, 1 h/day, 5 days/week. Animals were sacrificed at rest and the heart, liver, and soleus were removed for analysis. Percent of high and low affinity binding sites were determined by competitive binding experiments. Competition curves were generated using 12 concentrations of ICI-89406 (beta 1 antagonist) and ICI-118551 (beta 2 antagonist) to inhibit the total binding of (-) [125I] pindolol (IPIN). Maximal binding site number (Bmax) and affinity (KD) were determined by Scatchard analysis. Heart Bmax did not differ with age or training. An aging effect was observed in liver such that middle-aged and old animals had greater Bmax compared to young animals. In soleus, Bmax was not altered with training but decreased with age. While training had no affect on affinity in the liver and soleus, heart affinity increased with training in both the middle-aged (21%) and old (27%) animals. In soleus, affinity increased but remained unaltered in heart and liver with age. The ratio of beta 1:beta 2 receptors in the heart and liver did not differ with age or training. The influence of age and training on beta-adrenergic receptor characteristics appear to be tissue specific.

Aging

Acclimatization to high altitude increase muscle sympathetic activity both at rest and during exercise.

This investigation examined the relationship between alterations in plasma norepinephrine associated with 21 days of high-altitude exposure and muscle sympathetic activity both at rest and during exercise. Healthy sea level residents, divided into a control group (n = 5) receiving a placebo or a drug group (n = 6) receiving 240 mg/day of propranolol, were studied while at sea level, upon arrival (acute), and after 21 days of residence (chronic) at 4,300 m. Arterial norepinephrine levels and net leg uptake and release of norepinephrine were determine both at rest and during 45 min of submaximal exercise via samples collected from femoral arterial and venous catheters. Arterial norepinephrine levels increased significantly after chronic altitude exposure both at rest (84%) and during exercise (174%) compared with sea level and acute values. A net uptake of norepinephrine was found in resting legs at sea level (0.28 +/- 0.05 nmol/min) and with acute exposure (0.07 +/- 0.06 nmol/min); however, a significant switch to net leg norepinephrine release was observed with chronic altitude exposure (0.51 +/- 0.11 nmol/min). With exercise, a net release of norepinephrine by the leg occurred across all conditions with chronic exposure, again eliciting the greatest values (5.3 +/- 0.6, 8.0 +/- 1.7, and 14.4 +/- 3.1 nmol/min for sea level, acute, and chronic exposure, respectively). It was concluded that muscle sympathetic activity is significantly elevated both at rest and during submaximal exercise as a result of chronic high-altitude exposure, and muscle is a major contributor to the increase in plasma norepinephrine levels associated with prolonged altitude exposure. The presence of dense beta-blockade did not alter this adaptation to altitude.

Acclimatization

Influence of aging and endurance training on lactate dehydrogenase in liver and skeletal muscle.

The purpose of this investigation was to determine the effects of aging and endurance training on lactate dehydrogenase (LDH) activity and isozyme pattern in liver and skeletal muscle. Male Fischer 344 rats (n = 30) of three different age groups (young, 4 months; middle-aged, 12 months and old, 22 months) were trained on a treadmill at 75% running capacity for 1 h/day, five times per week for 10 weeks. Age-matched sedentary controls (n = 36) were used for comparison. Total LDH enzyme activity was measured spectrophotometrically; LDH isozymes were separated by native 5.5% polyacrylamide gel electrophoresis and quantified densitometrically. With increasing age, hepatic LDH activity decreased 28%. Old sedentary animals displayed significantly less (22%) hepatic LDH 5 than young and middle-aged animals, and significantly more (40%) hepatic LDH 4 than middle-aged animals. Training resulted in a significant decrease (38%) in total hepatic LDH activity in young rats only. Young animals displayed a significant increase in hepatic LDH 3 (28%), whereas middle-aged animals exhibited a significant decrease in hepatic LDH 3 (40%) with training. No change in total hepatic LDH activity was exhibited in middle-aged or old rats with training. Neither aging or training had a significant effect on LDH activity or isozyme pattern in extensor digitorum longus (EDL). Similarly, LDH activity was maintained in soleus with age, and isozyme pattern was only negligibly affected. We conclude that with age there is a decline in hepatic LDH activity and a decrease in the LDH 5 isozyme. Endurance training induced significant decreases in hepatic LDH activity of young animals. However, these decreases were not a result of shifts in isozymal pattern. Further, LDH activity was maintained in EDL and soleus muscle with age. Finally, endurance training did not have a significant effect on LDH activity or isozymal pattern of EDL or soleus.

Adaptation, Physiological

Coincidence of lactate threshold and HR-power output threshold under varied nutritional states.

The purpose of this study was to cross-validate the method of Conconi et al. (5) that purports to determine "anaerobic threshold" based on a deflection point between heart rate (HR) vs power output. Eight males (22.6 +/- 1.6 y) were tested with maximal progressive cycle ergometry under normal (NG) and glycogen-depleted (GD) conditions. During the last min of each stage, HR was monitored via EKG and blood was sampled for lactate determination. Computerized data analysis was then conducted to determine the deflection points for lines respectively fit to each HR vs power output (heart rate threshold; HRT) and lactate vs power output (lactate threshold; LT) distribution. Under NG conditions, HRT and LT occurred at 200.4 +/- 33.3 and 211.4 +/- 46.5 watts, respectively (equivalent to VO2 = 2.455 +/- 0.368 and 2.618 +/- 0.507 l/min), with a correlation of r = 0.68 between HRT vs LT (S.E.E. for prediction of LT from HRT = 36.7 watts). However, under GD conditions, HRT = 182.9 +/- 43.3 watts and LT = 227.0 +/- 41.1 watts (equivalent to VO2 = 2.395 +/- 0.413 and 2.944 +/- 0.578 l/min) with HRT vs LT r = -0.04 and S.E.E. = 44.4 watts. Across the two conditions, < 4% of the variance in the change in LT was accounted for by the change in HRT. These data indicated that 1) under NG conditions the modest association between HRT and LT was not causally-linked and 2) HRT was not a stable predictor of LT across varying nutritional states such as those common to prolonged exercise.

Adult

Role of norepinephrine in hepatic gluconeogenesis: evidence of aging and training effects.

This study examined the relationship among the sympathetic neurotransmitter norepinephrine (NE), hepatic gluconeogenesis, and glyconeogenesis in 63 (30 trained and 33 untrained) young (7 mo), middle-aged (15 mo), and old (25 mo) male Fischer 344 rats. Animals were trained 1 h/day, 5 days/wk for 10 wk at treadmill speeds of 75% of age-specific maximal capacity. Liver sections, removed at rest, were sliced and incubated in [14C]lactic acid and 0, 0.5, 1.0, 3.0, or 6.0 ng/ml NE. The rate of [14C]lactate incorporation into glucose was significantly greater in young compared with old animals in both training groups and at all NE concentrations. All trained animals had greater rates of glucose production from lactate than their untrained counterparts at 0.5, 1.0, 3.0, and 6.0 ng/ml NE. At each NE concentration, the old rats showed the lowest rates of glycogen synthesis from lactate. The untrained rats in all age groups were the least responsive to increases in NE concentration. Total hepatic glycogen synthase activity exhibited age-related declines as the young and middle-aged had significantly greater total activity compared with the old animals: 620.4 +/- 27.5, 590.0 +/- 37.9, and 436.3 +/- 44.5 disintegrations/min, respectively. No differences with training were found in total activity. The percent of glycogen synthase in the active form was significantly greater in young compared with old in both the trained (48.6 +/- 2.0 vs. 40.0 +/- 1.3% active) and untrained animals (44.7 +/- 2.2 vs. 35.4 +/- 1.5% active).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Exercise training does not compensate for age-related decrease in myocardial GLUT-4 content.

We assessed the effects of age and endurance exercise training (treadmill running at 75% maximal running capacity, 1 h/day, 5 days/wk for 10 wk) on the total concentration of insulin-regulatable glucose transporters (GLUT-4) and GLUT-4 mRNA levels in the myocardium of male Fischer 344 rats aged 7, 15, and 25 mo. Myocardial GLUT-4 concentration was quantified with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting and detected with a polyclonal antibody to the GLUT-4 transporter. Myocardial GLUT-4 mRNA levels were quantified with slot-blot analysis and a cDNA probe for GLUT-4. Myocardial GLUT-4 concentration in the 25-mo group decreased 27 and 20% compared with the 7- and 15-mo group, respectively (P < 0.0001 and P < 0.003). GLUT-4 mRNA also decreased significantly in the 25-mo group compared with the 7-mo group (20% in the trained and 11% in the untrained group, P < 0.05). Endurance training did not significantly affect myocardial GLUT-4 concentrations in any age group despite a significant increase in GLUT-4 mRNA in the 7- and 25-mo trained groups. In conclusion, myocardial GLUT-4 protein levels in the rat are significantly decreased with age but are unaffected by 10 wk of treadmill running.

Aging

Plasma catecholamine and lactate response during graded exercise with varied glycogen conditions.

The relationships between the lactate threshold (TLa), plasma catecholamines, and ventilatory threshold (TVE) were examined under normal and glycogen-depleted conditions. Nine male subjects performed a graded exercise test on a bicycle ergometer in a normal glycogen (NG) state and in a glycogen-depleted (GD) state to determine if manipulation of muscle glycogen content would affect their ventilatory, lactate, and catecholamine responses. High correlations were found between plasma lactate and the two catecholamines, epinephrine (r = 0.964) and norepinephrine (r = 0.965) under both conditions. The GD protocol resulted in a shift in the TLa to a later work rate; inflections in epinephrine and norepinephrine shifted in a coordinated manner. TVE and TLa occurred at similar work loads under NG conditions [67.2 +/- 1.5 and 65.6 +/- 2.3% maximal oxygen consumption (VO2max), respectively], but TLa occurred at a later work load (75.3 +/- 1.9% VO2max) compared with TVE (68.3 +/- 1.6% VO2max) under GD conditions. These results suggest a causal relationship between plasma lactate and epinephrine during a graded exercise test under the glycogen conditions studied. Although an association existed between ventilation and lactate, this relationship was not as strong.

Adult