Effects of aerobic and resistance exercise training on insulin action in the elderly

Background:   Aging is associated with a declining glucose tolerance, which is primarily caused by peripheral insulin resistance, and with a decline in physical activity. The aim of this study was to assess the effect of aerobic and resistance exercise training on insulin action in the elderly.
Methods:   Fourteen healthy male subjects (age: 65–73 years) were enrolled and divided into two exercise groups: resistance training (RT) or a combined aerobic and resistance training (CT). Subjects participated in each training program three times a week for 12 weeks. Before and after the training program, insulin action was determined using the euglycemic clamp technique at insulin infusion rates of 40 (low) or 400 (high) mU/m² per min. Body composition was measured by dual-energy X-ray absorptiometry (DXA).
Results:   Percent fat decreased significantly in both groups. Fat-free mass (FFM) tended to increase in the RT group ( P  = 0.054), but not in the CT group. In the CT group, the glucose infusion rate (GIR) increased 16.6% ( P  < 0.05) at the low insulin infusion rate and 21.7% ( P  < 0.01) at the high rate. In the RT group, GIR tended to increase at the low insulin infusion rate, but was not statistically significant ( P  = 0.052) and increased 9.9% ( P  < 0.05) at the high rate. When calculated per FFM, the increased insulin action persisted in the CT group ( P  < 0.01), but not in the RT group.
Conclusion:   The combination of aerobic and resistance training is more effective for improving the decreased insulin action in the elderly than resistance training alone.     

HMG-CoA reductase inhibitors promote cholesterol-dependent Akt/PKB translocation to membrane domains in endothelial cells

OBJECTIVE: Recent results have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors referred to as statins rapidly activate the protein kinase Akt/PKB in endothelial cells (ECs) and endothelial precursor cells (EPCs). This pathway is critical for cellular responses that contribute to angiogenesis and EC function including nitric oxide production, cellular survival and migration. METHODS: Here we tested whether statins control the translocation of recombinant and endogenous Akt to the plasma membrane of endothelial cells in a cholesterol-dependent manner. RESULTS: Low doses of statins rapidly induce the translocation of Akt to discrete sites in endothelial cell plasma membrane that colocalize with F-actin-positive, focal adhesion kinase (FAK)-negative lamellipodia and filopodia. This translocation event requires the lipid-binding, pleckstrin homology domain of Akt. Treatment with phosphoinositide 3-kinase (PI 3-kinase) inhibitors or the HMG-CoA reductase reaction product L-mevalonate blocks the translocation of Akt in response to statin stimulation. Furthermore, the ability of statins to promote Akt activation and translocation to the membrane is inhibited by cholesterol delivery to cells, but cholesterol loading had no effect on VEGF-induced Akt activation. CONCLUSIONS: These results suggest that statin activation of Akt signaling is mediated by the translocation of Akt to cholesterol-sensitive membrane structures within activated ECs.     

Cold pain prolongs gastric emptying of liquid but not solid meal: an electrical impedance tomography (EIT) study

Stressful stimuli are reported to affect gastric emptying. However, methods for measuring gastric emptying are, in themselves, stressful. Electrical impedance tomography (EIT) is a method for measuring gastric emptying noninvasively. We used EIT to measure gastric emptying of liquid and solid meals to determine the effect of cold pain stress on gastric emptying. EIT (DAS-01P APT system; University of Sheffield, UK) was carried out in six healthy women (age, 21.6 ± 0.4 [mean ± SD] years) who had ingested a liquid (potage, 263 g; 139 kcal) or solid (beef patty, 205 g; 435 kcal) test meal. Cold pain stimuli consisted of repeated immersions of the subject's non-dominant hand into ice water (4°C) for 1 min, with a 15-s recovery period between immersions, for a total of 20 min. For the control stimulus, water at 37°C was used. The cold pain stimulus was applied immediately after the ingestion of a test meal. All studies were carried out randomly in each subject at intervals of more than 1 week. With cold pain, the half emptying time of the liquid meal was significantly greater than that with the control stimulus (47.6 ± 26.1 min vs 28.1 ± 10.8 min, P < 0.05). For the solid meal, the half emptying time did not differ between stimuli (101.9 ± 44.8 min with cold pain vs 92.6 ± 30.5 min with control stimulus). There were no significant differences in lag time between the liquid and solid meals. Cold pain stress delayed gastric emptying of liquid but not solid meals. Received: September 28, 1999 / Accepted: February 25, 2000     

Westernized food habits and concentrations of serum lipids in the Japanese

To investigate the association of westernized food habits and concentrations of serum lipids in the Japanese, we studied 1200 healthy Japanese living in Hiroshima prefecture and 1483 ethnic Japanese from Hiroshima prefecture living in the Hawaii Islands and Los Angeles. The nutritional assessments were made by the same dietitians. No major difference was observed in the total energy intake between the Japanese and the Japanese-Americans in both males and females. However, the intake of animal fat and simple carbohydrates (especially fructose) were markedly greater, and that of complex carbohydrates lower, in the Japanese-Americans compared with the Japanese. The mean serum cholesterol (CH), LDL-CH and serum triglyceride (TG) levels were significantly higher in the Japanese-Americans in both sexes. The mean HDL-CH concentration was similar between the two groups in males, but it was approximately 7 mg/dl higher in Japanese-American females. Using the 75 percentile values of CH and TG in the Japanese in Hiroshima, the frequency of WHO types IIa and IIb hyperlipidemia was about twice as high in the Japanese-Americans. These results suggest that westernized food habits in the Japanese include qualitative changes in animal fat, simple carbohydrate and complex carbohydrate diet rather than an increase in the total energy intake. These changes are associated with marked increases in the concentrations of serum CH and TG and increased prevalence of types IIa and IIb hyperlipidemia.     

Measurement of varicella-zoster virus (VZV)-specific cell-mediated immunity: comparison between VZV skin test and interferon-gamma enzyme-linked immunospot assay

Cell-mediated immunity (CMI) is critical for the prevention and control of varicella-zoster virus (VZV)-related disease. To assess CMI to VZV, a varicella skin test and interferon-gamma enzyme-linked immunospot (ELISPOT) assay were both performed in healthy volunteers, and the results were compared. A total of 151 subjects were examined: 16 aged 20-29 years, 26 aged 30-39 years, 18 aged 40-49 years, 73 aged 50-59 years, and 18 aged 60-69 years. All were seropositive by a glycoprotein antigen-based enzyme-linked immunosorbent assay (gpELISA). Skin test reactivity was significantly correlated with the ELISPOT count, and both decreased with increasing age, indicating an age-dependent decline in CMI to VZV. In contrast, the antibody titer obtained by the gpELISA did not correlate with skin test reactivity. The results suggest that the skin test and ELISPOT assay are both reliable for assessing CMI to VZV and can easily be applied to screen individuals susceptible to the development of herpes zoster.     

Immunohistochemistry of γ‐H2AX as a method of early detection of urinary bladder carcinogenicity in mice

Phosphorylated histone H2AX (γ‐H2AX) has been demonstrated as a DNA damage marker both in vitro and in vivo. We previously reported the effects of genotoxic carcinogens in the urinary bladder of rats by immunohistochemical analysis of γ‐H2AX using samples from 28‐day repeated‐dose tests. To evaluate the application of γ‐H2AX as a biomarker of carcinogenicity in the bladder, we examined species differences in γ‐H2AX formation in the urinary bladder of mice. Six‐week‐old male B6C3F₁ mice were treated orally with 12 chemicals for 4 weeks. Immunohistochemical analysis demonstrated that N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine, p‐cresidine and 2‐acetylaminofluorene (2‐AAF), classified as genotoxic bladder carcinogens, induced significant increases in γ‐H2AX levels in the bladder urothelium. In contrast, genotoxic (2‐nitroanisole, glycidol, N‐nitrosodiethylamine and acrylamide) and non‐genotoxic (dimethylarsinic acid and melamine) non‐bladder carcinogens did not upregulate γ‐H2AX. Importantly, 2‐nitroanisole, a potent genotoxic bladder carcinogen in rats, significantly increased the proportion of γ‐H2AX‐positive cells in rats only, reflecting differences in carcinogenicity in the urinary bladder between rats and mice. Significant upregulation of γ‐H2AX was also induced by uracil, a non‐genotoxic bladder carcinogen that may be associated with cell proliferation, as demonstrated by increased Ki67 expression. 2‐AAF caused γ‐H2AX formation mainly in the superficial layer, together with reduced and disorganized expression of uroplakin III, unlike in rats, suggesting the mouse‐specific cytotoxicity of 2‐AAF in umbrella cells. These results suggest γ‐H2AX is a useful biomarker reflecting species differences in carcinogenicity in the urinary bladder.     

Phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) regulates neuronal microtubule depolymerase kinesin, KIF2A and suppresses elongation of axon branches

Neuronal morphology is regulated by cytoskeletons. Kinesin superfamily protein 2A (KIF2A) depolymerizes microtubules (MTs) at growth cones and regulates axon pathfinding. The factors controlling KIF2A in neurite development remain totally elusive. Here, using immunoprecipitation with an antibody specific to KIF2A, we identified phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) as a candidate membrane protein that regulates the activity of KIF2A. Yeast two-hybrid and biochemical assays demonstrated direct binding between KIF2A and PIPKα. Partial colocalization of the clusters of punctate signals for these two molecules was detected by confocal microscopy and photoactivated localization microscopy. Additionally, the MT-depolymerizing activity of KIF2A was enhanced in the presence of PIPKα in vitro and in vivo. PIPKα suppressed the elongation of axon branches in a KIF2A-dependent manner, suggesting a unique PIPK-mediated mechanism controlling MT dynamics in neuronal development.     

Constructing an index of physical fitness age for Japanese elderly based on 7-year longitudinal data: sex differences in estimated physical fitness age

A standardized method for assessing the physical fitness of elderly adults has not yet been established. In this study, we developed an index of physical fitness age (fitness age score, FAS) for older Japanese adults and investigated sex differences based on the estimated FAS. Healthy elderly adults (52 men, 70 women) who underwent physical fitness tests once yearly for 7 years between 2002 and 2008 were included in this study. The age of the participants at the beginning of this study ranged from 60.0 to 83.0 years. The physical fitness tests consisted of 13 items to measure balance, agility, flexibility, muscle strength, and endurance. Three criteria were used to evaluate fitness markers of aging: (1) significant cross-sectional correlation with age; (2) significant longitudinal change with age consistent with the cross-sectional correlation; and (3) significant stability of individual differences. We developed an equation to assess individual FAS values using the first principal component derived from principal component analysis. Five candidate fitness markers of aging (10-m walking time, functional reach, one leg stand with eyes open, vertical jump and grip strength) were selected from the 13 physical fitness tests. Individual FAS was predicted from these five fitness markers using a principal component model. Individual FAS showed high longitudinal stability for age-related changes. This investigation of the longitudinal changes of individual FAS revealed that women had relatively lower physical fitness compared with men, but their rate of physical fitness aging was slower than that of men.