Ken D. Sumida

Training enhanced hepatic gluconeogenesis: the importance for glucose homeostasis during exercise.

Endurance training has long been known to improve the individuals resistance to exercise-induced hypoglycemia. Traditionally attributed to a reduction in glucose uptake subsequent to enhanced fat oxidation, this issue has only recently been directly addressed. This paper briefly reviews the evidence for reduced glucose uptake versus enhanced glucose production in the improved hypoglycemic resistance following training. While whole body glucose removal and production may be reduced following training, this has only been demonstrated under exercising conditions in which glycemia demonstrates little deviation from rest. Under exercise conditions where untrained animals demonstrate substantial reductions in blood glucose, training enhanced hypoglycemic resistance has been shown to result entirely from enhanced glucose production via gluconeogenesis. Using the in situ perfused liver preparation, the authors have provided direct evidence for a training enhanced hepatic gluconeogenic capacity. The site of adaptation within the gluconeogenic pathway has now been constrained to below the level of the triose phosphates. Lack of evidence for suppressed skeletal muscle glucose uptake following training, a uniform observation for humans and rats, is also discussed. It is concluded that the improved hepatic gluconeogenic capacity of endurance trained individuals, at least in rats, is critical to their demonstrated resistance to exercise-induced hypoglycemia.

Sex Differences in Hepatic Gluconeogenic Capacity After Chronic Alcohol Consumption

Alcohol-induced hypoglycemia has traditionally been attributed to the amount of ethanol consumed rather than any inherent decline in glucose output capacity by the gluconeogenic organs and/or an increase in skeletal muscle glucose uptake. Further, while the potential for sex differences that might impact glucose homeostasis following chronic alcohol consumption has been recognized, direct evidence has been noticeably absent. This paper will provide a brief review of past and present reports of the potential for sex differences in glucose homeostasis following chronic ethanol consumption. This paper will also provide direct evidence from our laboratory demonstrating sex differences from chronic alcohol consumption resulting in a decrement in glucose appearance and more importantly, a specific decline in hepatic gluconeogenic (HGN) capacity in the absence and presence of ethanol. All our studies involved 8 weeks of chronic alcohol consumption in male and female Wistar rats, as well as a 24 to 48 hour fast to deplete hepatic glycogen stores. Under the conditions of chronic alcohol consumption and an acute dose of ethanol, we provide in vivo evidence of an early decline in whole body glucose appearance in females fed an ethanol diet compared to controls. While the decline was also observed in males fed the alcohol diet, it occurred much later compared to ethanol fed females. The site for the decline in whole body glucose production (i.e., either the kidneys or the liver) was beyond the scope of our prior in vivo study. In a follow-up study using the in situ perfused liver preparation, we provide additional evidence for a specific reduction in HGN capacity from lactate in ethanol fed females compared to ethanol fed males in the absence of alcohol in the perfusion medium. Finally, employing the isolated hepatocyte technique, we report decrements in HGN from lactate in ethanol fed females compared to ethanol fed males in the presence of ethanol in the incubation medium. The mechanism for the specific decline in HGN within the liver of ethanol fed females remains to be determined. To the extent that our observations in animals can be extrapolated to humans, we conclude that alcoholic women are more susceptible to ethanol-induced hypoglycemia compared to alcoholic men.

Better Cognitive Control of Emotional Information is Associated with Reduced Pro-Inflammatory Cytokine Reactivity to Emotional Stress

Abstract Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of the key pro-inflammatory cytokines IL-1β, IL-6, and IL-8 were measured before and after the experimental manipulation, and following the last cytokine sample, we assessed participants’ cognitive control of emotional information using an emotional Stroop task. We also assessed participants’ cortisol levels before and after the manipulation to verify that documented effects were specific to cytokines and not simply due to increased nonwater salivary output. As hypothesized, the emotional stressor triggered significant increases in IL-1β, IL-6, and IL-8. Moreover, even in fully adjusted models, better cognitive control following the emotional (but not control) video predicted less pronounced cytokine responses to that stressor. In contrast, no effects were observed for cortisol. These data thus indicate that better cognitive control specifically following an emotional stressor is uniquely associated with less pronounced pro-inflammatory cytokine reactivity to such stress. These findings may therefore help explain why superior cognitive control portends better health over the lifespan.

Temporal effects of testosterone propionate injections on serum lipoprotein concentrations in rats.

UNLABELLED The chronic abuse of androgenic anabolic steroids, a group of synthetic derivatives of testosterone, to improve athletic performance have demonstrated compromised serum lipoprotein concentrations reflecting an elevated risk for cardiovascular disease. While the detrimental alterations in the lipoprotein profile have been reported consistently for orally administered androgenic anabolic steroids, the reports examining the effects of parenteral administration of testosterone upon the lipid profile remain equivocal. PURPOSE The purpose of this study was to determine whether compromised serum lipoprotein concentrations would be manifest in rats receiving testosterone injections (twice per week) over the time course of 7 wk. METHODS Male rats were randomly assigned to either an experimental group (dose per injection, 3 mg x kg(-1) testosterone propionate solubilized in 1 mL of safflower oil) or a control group (injected with an isovolumic amount of safflower oil alone). The effects of the steroid regimen on the serum lipoprotein profiles were followed after 1, 3, 5, and 7 wk of injections. To assess the relative effects of testosterone propionate, testicular mass was determined at the time of sacrifice. RESULTS Testicular mass (mean +/- SE) was significantly lower (P<0.01) in the experimental group, 3.08+/-0.03 g, compared with that in controls, 3.82+/-0.05 g, by week 3 and continued to decline for the remainder of the steroid regimen, reaching a nadir of 2.70+/-0.01 g at week 5. No significant differences were observed between groups for total serum cholesterol, serum triacylglycerols, or serum low density lipoprotein (LDL)-C at any time point. However, at week 7, serum high density lipoprotein (HDL)-C (mean +/- SE) was significantly lower (P<0.02) in the testosterone treated animals, 32+/-2 mg x dL(-1), compared with that in controls, 47+/-2 mg x dL(-1). As a result, the ratio of total cholesterol to HDL-C (mean +/- SE) significantly increased (P<0.02) by the seventh week in the testosterone treated group, 3.5+/-0.2, versus controls, 2.5+/-0.2. CONCLUSIONS The results suggest that while testosterone propionate injections elicit a reduction in testicular mass within 3 wk, the lipoprotein profile is not altered until week 7. Further, the only compromised parameter under the conditions of this study is the decrease in serum HDL-C.

Zumba® Fitness workouts: are they an appropriate alternative to running or cycling?

A sedentary lifestyle (i.e., physically inactive) has been associated with a variety of diseases such as: obesity, type II diabetes, and heart disease. Chronic aerobic exercise can be used as a prophylactic against these diseases. However, the challenges for individuals, prior to engaging in a training program for disease prevention, include the selection of an appropriate aerobic exercise as well as longterm compliance. Running or cycling is the traditional modes of aerobic exercise used to minimize the risk of disease and maintain a healthy body weight. In this regard, the American College of Sports Medicine recommends a caloric expenditure of 300 kcal per exercise session [1]. Numerous studies examining running and cycling have reported caloric expenditures well above 300 kcal per exercise session [4– 8]. Running and cycling have also been reported to elicit increases in plasma beta (b) endorphin levels [4–8, 12, 13]. b endorphin can be released by the pituitary gland in response to exercise of sufficient intensity and duration and has been associated with euphoria and exercise addiction in what has been referred to by the fitness community as ‘‘runner’s high’’ [2, 10]. An exercise-induced elevation in b endorphin would provide additional support for the efficacy of the aerobic activity (in the prevention of disease) by increasing the likelihood of long-term compliance. While running and cycling have been the traditional activities to engage in aerobic activity, fitness classes and home exercise DVDs have become an attractive alternative. In this regard, dance fitness DVDs, as employed by Zumba Fitness, have become extremely popular. Originating in Columbia, South America, Zumba Fitness was created as a Latin-inspired dance fitness program that combines various types of dance elements (e.g. hip-hop, samba, etc.) to music as a method to engage in aerobic exercise as an alternative to running or cycling. To date, only one study has specifically examined the efficacy of Zumba Fitness as an appropriate workout for health benefits. Luettgen et al. [9] used exercise heart rates to predict the oxygen consumption expended during a Zumba class that lasted an average of 39 min. Specifically, with use of an incremental treadmill test, they employed a linear regression equation between heart rate and oxygen consumption (VO2). Based upon a subject’s heart rate during a Zumba class, they estimated the oxygen consumption to determine caloric expenditure [9]. They reported an average exercise heart rate of 154 bpm (79 % of HR max) and an average caloric expenditure of 370 kcal per class [9] suggesting that a Zumba Fitness workout may be an appropriate alternative to running or cycling. Estimates of VO2 via exercise heart rates and the subsequent determination of caloric expenditure, as employed by Luettgen et al. [9], would seem appropriate given the difficulty in measuring VO2 during aerobic dance exercises. Given the differences in movements between running on a treadmill and dance, there may be limitations with the use of treadmill heart rates to predict VO2 during a dance workout. Currently, no one has actually measured oxygen consumption during dance exercises to substantiate the E. Sternlicht Department of Kinesiology, Occidental College, Los Angeles, CA 90041, USA

Strength training does not alter the effects of testosterone propionate injections on high-density lipoprotein cholesterol concentrations.

The purpose of the study was to examine the long-term effects of a high-volume strength training program (vertical ladder climbing) and testosterone propionate injections (intraperitoneal) on serum lipid and lipoprotein concentrations in male Sprague-Dawley rats. The animals were randomly divided into a testosterone (T)-treated group (dose per injection, 2.5 mg/kg testosterone propionate solubilized in 1 mL safflower oil) and a control (C) group (injected with an isovolumic amount of safflower oil alone). Animals were further divided into a strength-trained group (E) and a sedentary group (S). The 10-week resistance training program consisted of weights (100% of body mass) appended to the tail as the animal climbed an 85-cm ladder to volitional fatigue. Following 10 weeks of strength training and testosterone injections, body weight was not significantly different between the main effects of strength training exercise (TE + CE v TS + CS) and testosterone injections (TE + TS v CE + CS) or between groups. Testicular mass (mean +/- SE) was measured as a relative indicator of testosterone effects. Both TE and TS had significantly reduced testicular mass (2.56 +/- 0.04 and 2.38 +/- 0.03 g, respectively) compared with CE and CS (3.49 +/- 0.03 and 3.49 +/- 0.04 g, respectively). No significant differences were observed between groups for total serum cholesterol, serum triglycerides, or serum low-density lipoprotein cholesterol (LDL-C). In contrast, significant decreases in high-density lipoprotein cholesterol (HDL-C) were observed for both TE (26.7 +/- 1.6 mg/dL) and TS (27.5 +/- 1.3 mg/dL) compared with CE (48.7 +/- 2.9 mg/dL) and CS (43.5 +/- 2.6 mg/dL). As a result, the total cholesterol to HDL-C ratio was significantly greater for TS + TE (4.7 +/- 0.1) compared with CS + CE (2.9 +/- 0.2). These observations suggest that in animals, a 10-week program of high-volume strength training does not elicit any beneficial effect on the lipid or lipoprotein status, nor does it attenuate the altered lipoprotein profile induced by testosterone propionate injections.

Interrupted Resistance Training and BMD In Growing Rats

A resistance training program, where the exercise was uninterrupted (UT, i.e. continuous repetitions) was compared against another resistance training program where the exercise was interrupted (IT, i.e. 2 exercise sessions during a training day) for enhancing bone modeling and bone mineral density (BMD) in maturating animals. The total volume of work performed between the two resistance training programs was equivalent by design. Young male rats (approximately 8 weeks old) were randomly divided into Control (Con, n=8), UT (n=8) and IT (n=7) resistance trained groups. The UT and IT groups were conditioned to climb a vertical ladder with weights appended to their tail 3 days/week for 6 weeks. After the 6 week training regimen (Mean+/-SD), tibial BMD (assessed via DXA) was significantly greater for UT (0.237+/-0.008 g/cm(2)) and IT (0.238+/-0.005 g/cm(2)) compared to Con (0.223+/-0.004 g/cm(2)). Further, serum osteocalcin (OC) was significantly greater for UT (45.65+/-2.83 ng/ml) and IT (46.33+/-4.60 ng/ml) compared to Con (37.86+/-4.04 ng/ml). There was no significant difference in BMD or serum OC between UT and IT groups. The results indicate that both resistance training programs were equally effective in elevating BMD in growing animals.

Interrupted Vs. Uninterrupted Training on BMD During Growth

This study compared a resistance training program where the exercise was uninterrupted (UT, i.e., continuous repetitions) against a resistance training program where the exercise was interrupted (IT, i.e., 3 exercise sessions during a training day) for enhancing bone modeling and bone mineral density (BMD) in maturating animals. The total volume of work performed between the two resistance training programs was equivalent by design. 24 young male rats were randomly divided into Control (Con, n = 8), UT (n = 8) and IT (n = 8) resistance trained groups. The UT and IT groups were conditioned to climb a vertical ladder with weights appended to their tail 3 days/wk for 6 wks. After the 6-wk program, serum osteocalcin was not significantly different between groups, whereas the adjusted urinary deoxypyridinoline (DPD) was significantly lower for both UT (81.03 +/- 5.53) and IT (88.30 +/- 7.29) compared to Con (128.13 +/- 9.99). Tibial BMD (assessed via DXA) was significantly greater for UT (0.222 +/- 0.005 g/cm (2)) and IT (0.219 +/- 0.003 g/cm (2)) when compared to Con (0.205 +/- 0.004 g/cm (2)). There was no significant difference in DPD or BMD between UT and IT groups. The results indicate that both interrupted and continuous, uninterrupted resistance training programs were equally effective in stimulating bone modeling.

Differential effects of alcohol upon gluconeogenesis from lactate in young and old hepatocytes.

The purpose of this study was to determine the effect of age upon hepatic gluconeogenesis (HGN) from lactate in the presence of various concentrations of alcohol from young (3 months) and old (24 months) male rats. After a 24-hour fast, livers were perfused with collagenase and the hepatocytes were isolated. Aliquots of the cell suspension were placed in Krebs-Henseleit buffer and incubated with lactate, [U-(14)C]lactate, and nine different concentrations of ethanol (EtOH) for 30 min. Dose-effect curves were generated for the determination of maximal and half-maximal alcohol-induced inhibition on gluconeogenesis. There were no significant differences in basal HGN (lactate only and no EtOH) between young and old hepatocytes, 86.9+/-6.3 nmol/mg protein/30 min. The addition of ethanol significantly reduced HGN from lactate in both groups. At the highest ethanol concentration (15 mM), the glucose production was inhibited more from old, 46.1+/-1.2 nmol/mg protein/30 min, compared to young hepatocytes, 56.0+/-1.6 nmol/mg protein/30 min. The greater age-related reduction in HGN was confirmed by the minimal glycogenolysis, and the concomitant decline in [U-(14)C]glucose production, lactate uptake, and [U-(14)C]lactate uptake. The results suggest that alcohol elicits a greater inhibition upon HGN from lactate in old compared to young liver cells.

Equal BMD After Daily or Triweekly Exercise in Growing Rats

The purpose of this study was to examine the efficacy of continuous resistance training (3 days/wk) compared to interrupted resistance training where 20-24 h separated an exercise bout (i. e. 6 days/wk) for enhancing bone mineral density (BMD) in growing male rats. The total volume of work performed per week between the two resistance training programs was equivalent by design. Young male rats were randomly divided into Control (Con, n=9), 3 days/wk resistance trained group (RT3, n=9), and 6 days/wk resistance trained group (RT6, n=9). The RT3 and RT6 groups were conditioned to climb a vertical ladder with weights appended to their tail for a total of 6 wks. After 6 wks, BMD (assessed via DXA) from the left tibia was significantly greater for RT3 (0.242+/-0.004 g/cm (2)) and RT6 (0.244+/-0.004 g/cm (2)) compared to Con (0.226+/-0.003 g/cm (2)). Further, serum osteocalcin (oc, in ng/ml) was significantly greater for RT3 (75.8+/-4.4) and RT6 (73.5+/-3.8) compared to Con (53.4+/-2.4). There was no significant difference in BMD or serum OC between RT3 and RT6 groups. The results indicate that both resistance training programs were equally effective in elevating bone mineral density in young, growing rats.