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Biomedical subjects

M J Rosenthal

Publications and source records attributed to M J Rosenthal.

At least 19 recordsLinked to original sources
PubMed2001

Effects of arachidonic acid and cyclo (his-pro) on zinc transport across small intestine and muscle tissues.

Previously we have shown that arachidonic acid (AA) plus zinc or cyclo (his-pro) (CHP) plus zinc improve clinical signs of diabetes in streptozotocin-induced diabetic rats. Since streptozotocin destroys pancreatic beta-cells, we hypothesize that the effect of either AA or CHP, plus zinc on glucose metabolism is via mobilization of intracellular zinc which in turn stimulates glucose uptake by peripheral tissues. We now report the relationship between zinc and AA and between zinc and CHP in controlling zinc influx and efflux across hindlimb muscle cells isolated from three-month old rats. Although CHP increased muscle zinc influx in a dose-dependent manner, AA was not effective. However, AA was more effective in stimulating zinc efflux than CHP. We have previously demonstrated that AA stimulates intestinal zinc uptake and absorption, and now present evidence that CHP also influences intestinal zinc transport. These results suggest that both AA and CHP affect glucose uptake in muscle cells via stimulating intestinal zinc absorption and muscle cell zinc flux.

Animals↗
PubMed2001

Synergistic antidiabetic activities of zinc, cyclo (his-pro), and arachidonic acid.

Previous studies have already shown that prostate extract (PE) has antidiabetic activity when given to animals and humans. In this study, we explore whether this antidiabetic activity is related to the high concentrations of zinc, cyclo (his-pro) (CHP), and the prostaglandin precursor, arachidonic acid (AA), in prostate tissue. When streptozotocin-induced diabetic rats were given drinking water containing 10 mg/L zinc and 100 mg/L PE for 3 weeks, fasting blood glucose levels and glucose clearance rates, but not plasma insulin levels, were significantly lower than at pretreatment. In subsequent experiments, blood glucose levels in rats given PE for 3 weeks were significantly lower than in rats given distilled water or 10 mg/L zinc alone. However, in rats given 100 mg/L CHP with zinc, blood glucose levels were also lower than in rats given PE alone. Time-course studies in diabetic rats given drinking water containing 20 mg/L Zn, 20 mg/L L-histidine, and 10 mg/L CHP showed that blood glucose levels dropped 209 +/- 53 mg/dL in 1 day and stayed low for 2 weeks. When CHP was replaced with 100 mg AA/L, blood glucose levels dropped 230 +/- 64 mg/dL in 5 days, but returned to the original values 11 days later. Growth rate improved and water consumption decreased significantly in CHP- and AA-treated diabetic rats. High intake of L-histidine and testosterone increased blood glucose concentrations in diabetic rats. To determine optimal dosages of CHP and AA, we gave rats drinking water containing 10 mg/L Zn and 0.5 mg/L L-histidine with various concentrations of CHP or AA. The most effective doses for reducing blood glucose levels were 0.32 mg CHP/kg/day and 11 mg AA/kg/day. These data suggest that the active antidiabetic ingredients in the PE are CHP, zinc, and AA or its precursors.

Animals↗
PubMed1998

Effects of bovine prostate powder on zinc, glucose, and insulin metabolism in old patients with non-insulin-dependent diabetes mellitus.

Since rabbit prostate extract strongly stimulated intestinal zinc absorption and improved the diabetic condition of streptozotocin-induced diabetic rats, we examined the effects of 200 mg bovine prostate powder supplemented with 20 mg zinc (Pro-Z) on the clinical manifestations of older male patients with type II diabetes. Twenty-two male patients who received Pro-Z capsules two to four times per day for 3 months showed reduced mean fasting blood glucose levels from 202 to 169 mg/dL, hemoglobin A1C-(HbA1C) concentrations from 12.2% to 9.5%, and mean values for the 3-hour area response above the fasting glucose concentration (TAFGC) from 141 to 102 mg glucose/dL/h. In eighteen patients who received placebo, mean values for fasting blood glucose decreased from 167 to 165 mg/dL and HbA1C from 10.4% to 10.2%, and for TAFGC increased from 121 to 126 mg glucose/dL/h. No detrimental changes occurred in the liver and kidney function of patients receiving either Pro-Z or placebo. However, blood cholesterol and low-density lipoprotein in patients receiving Pro-Z decreased slightly, whereas values in the placebo group tended to increase. The mean fasting plasma insulin decreased 15.5 to 13.8 microU/mL in subjects given Pro-Z, while the zinc concentration increased from 1.21 to 1.39 microg/mL. In contrast, the mean value for plasma insulin in the placebo group changed from 14.4 to 15.4 microU/mL (worsened), and for zinc, from 1.24 to 1.30 microg/ml. Interestingly, fasting urinary glucose concentrations in subjects given Pro-Z decreased from 1,249 to 378 mg/dL, whereas in those given placebo the values changed from 877 to 778 mg/dL. Since plasma zinc concentrations in both the placebo and the Pro-Z group were normal, these results suggest that biochemical constituents in the prostate including zinc may be involved in controlling glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

Aged↗
PubMed1998

Hospitalization and mortality of diabetes in older adults. A 3-year prospective study.

OBJECTIVE: In light of increased fatality from acute events and the increased frequency of chronic complications, life expectancy might well be shortened in older patients with diabetes. The current studies investigated factors affecting the likelihood of dying or being hospitalized in older patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 135 older patients with diabetes were followed for 3 years after predictive factors were evaluated and compared with a cohort of patients without diabetes. RESULTS: Mortality was only 3,250 per 100,000 patient-years, similar to that for patients without diabetes, but the frequency of hospitalizations was more than twice as high in patients with diabetes. Five factors predicted hospitalization and death. Of these, the geriatric depression score was the best predictor of these poor outcomes. CONCLUSIONS: Older patients with diabetes were hospitalized more often than those without diabetes, but mortality was similar. Dysphoria is a major predictor of poor outcomes in older patients with diabetes.

Aged↗
PubMed1997

Effects of relaxation training on glucose tolerance and diabetic control in type II diabetes.

The present study examined the effects of progressive relaxation training and EMG biofeedback on acute glucose disposal in diabetic subjects, as measured by glucose tolerance and three other measures of diabetic metabolic control. Twenty subjects with non-insulin-using Type II diabetes took part in progressive relaxation training and EMG biofeedback in a pre-post treatment versus wait-list experimental design. Treatment effects were assessed on glucose tolerance along with three measures of diabetic control: fasting blood glucose, two-hour postprandial blood glucose, and fructosamine. Stress reduction and relaxation was assessed with two physiological measures and two subjective questionnaires. The training program produced significant reductions in stress, as measured by State Anxiety, and significant changes in physiological measures of muscle activity and skin conductance compared to the control condition. However, no changes were found in glucose tolerance (while practicing relaxation) nor in any of the three measures of general diabetic metabolic control. The major implication of this study is that relaxation training does not appear to directly improve diabetic control in mildly stressed non-insulin-using Type II diabetic patients.

Diabetes Mellitus, Type 2↗
PubMed1996

A wheelchair cushion designed to redistribute sites of sitting pressure.

OBJECTIVES: Despite the diversity of wheelchair cushions currently in clinical use, pressure on bony prominences continues to be a major problem for wheelchair-bound patients, and the incidence of pressure ulcers remains high. No static surface has been reported to reduce resting pressure under the ischial tuberosities to below that of capillary pressure, which may well be the threshold for inducing tissue damage. An entirely new form of seating was designed to decrease absolute pressure using a prosthetic fitting technique analogous to a below-the-knee prosthesis. DESIGN: A repeated measures randomized design was used to test differences between the experimental (TCS) and three other standard cushions. SETTING: A Veterans Medical Center outpatient service. PATIENTS: Wheelchair-bound volunteer subjects, n = 47, were selected who weighed more than 60kg. MAIN OUTCOME MEASURES: Pressures were measured by a standard air pressure pad and also by a computer-linked array of pressure transducers. The grid was standardized and used to generate topographic maps for each site over time. These data were used to measure the seating interface pressures. RESULTS: There was a significant main effect of cushion over site, F = 131 for left ischial tuberosity. Pressure were lowest while patients sat on the experimental seat and differences were significant at all time points. Using 1psi as presumed capillary pressure, frequency of success at achieving this pressure threshold was greatest for the experimental seat, p < .001. This difference persisted throughout the 30 minutes of testing. CONCLUSIONS: A computerized pressure grid was developed that allowed evaluation of anatomically localized pressures. The prosthetically designed TCS displays lower seating pressures than any other cushion tested. Consistent and sustained pressures were below the postulated threshold for tissue damage.

Adult↗
PubMed1996

Alterations of adenylyl cyclase-linked G proteins in rat liver during aging.

beta-Adrenergic stimulation of adenylyl cyclase in rat liver increases during aging. We examined whether this increase is related to alterations in the stimulatory and inhibitory G proteins (Gs and Gi) linked to adenylyl cyclase. Levels of immunoreactive alpha- and beta-subunits of Ga and Gi in liver plasma membranes from 6-, 12-, 18-, and 24-mo-old rats were unchanged with age, as was pertussis toxin-catalyzed [32P]ADP ribosylation of Gi alpha. Cholera toxin-catalyzed [32P]ADP ribosylation of Ga alpha and Gs bioactivity, assessed as reconstitution of adenylyl cyclase activity in S49 cyc- cell membranes, increased two- to threefold between 6 and 12-18 mo, and declined by 24 mo. Recombinant ADP ribosylation factor (ARF) enhanced cholera toxin labeling of Gs alpha at all ages, yet abolished the increase in toxin labeling at 12-18 mo. Auto-ADP ribosylation of the cholera toxin A1 peptide also increased transiently with age. Alteration of Gs alpha, as reflected by increased cholera toxin labeling and Gs bioactivity, may be involved in the regulation of beta-adrenergic-responsive adenylyl cyclase in rat liver during aging. Moreover, changes in endogenous ARF levels could contribute to age differences in cholera toxin labeling of Gs alpha.

ADP-Ribosylation Factors↗
PubMed1994

Serum glucose, glucose tolerance, corticosterone and free fatty acids during aging in energy restricted mice.

Energy restriction, the only method known to increase maximum life span in laboratory animals, was used as a tool to test hypotheses regarding possible mechanisms of aging. Serum glucose and corticosterone (CS) concentrations in mice of a long-lived hybrid mouse strain, aged 7, 17, and 29 months, and on 50%, 80%, and 100% of ad libitum intake, were measured. Serum glucose and CS concentrations were also measured in response to intraperitoneal (i.p.) glucose challenge in mice at ages 7 and 29 months. Serum glucose and CS concentrations were also measured at several time points over 36 h, to assess their diurnal variation. There were no differences in single fasting glucose concentrations in 7- and 29-month-old mice at the same degree of energy restriction, but energy restriction decreased glucose concentrations. Serum CS concentrations were generally increased restricted animals with respect to fully fed ones. Average serum glucose concentrations were found to be significantly decreased by dietary restriction. Glucose tolerance curves were unchanged by age in ad libitum fed or 50% restricted animals, but in 80% ad libitum groups, older animals showed evidence of decreased glucose tolerance with respect to young animals. For each age, peak serum glucose concentrations after i.p. glucose loading varied with degree of energy restriction, with more severely restricted animals showing less glucose tolerance. Average serum CS concentrations were elevated at 7 months by restriction, especially at night and long after feeding, but we found no differences with age or diet in average CS concentrations. Our serum glucose results support the hypothesis that nonenzymatic glycation is mechanistically involved in normal aging. Our serum CS results do not support the hypothesis that CS contributes significantly to the pathophysiology of normal aging in mice.

Aging↗
PubMed1993

Acute autonomic responses to postural change, Valsalva maneuver, and paced breathing in older type II diabetic men.

PURPOSE: To examine the effects of advanced age and diabetes on the response to standard tests of cardiovascular reflexes. DESIGN: Group comparison. SETTING: Psychophysiology laboratory, Department of Veterans Affairs Medical Center. PATIENTS: Sixteen elderly male (67-81 years old) non-insulin dependent diabetic subjects without hypertension and nine elderly male (63-77 years old) controls. MAIN OUTCOME MEASURES: Continuous (beat-by-beat) measures of heart rate, systolic blood pressure, diastolic blood pressure, and skin conductance were studied during tests of Valsalva maneuver, deep breathing, and postural change from sitting to standing. RESULTS: In comparison with elderly controls, the diabetic patients showed altered cardiovascular responses in measures of heart rate variability during Valsalva and standing. None of the subjects evidenced frank postural hypotension, but there was a greater fall in diastolic blood pressure immediately after standing for the diabetic patients compared with the controls. There was also a significant relationship between this response and decreased heart rate variability during Valsalva. CONCLUSIONS: Older type II diabetic patients compared with healthy controls had mild cardiovascular abnormalities. These results parallel those of studies comparing younger diabetics and controls.

Age Factors↗
PubMed1992

Role of hypothalamic paraventricular nucleus alpha- and beta-adrenergic receptors in regulation of blood glucose, free fatty acids and corticosterone.

The potential roles of adrenergic and noradrenergic terminals in the hypothalamic paraventricular nucleus in the regulation of blood glucose and free fatty acids, the two major metabolic fuels, were examined. Corticosterone was also measured, both to assess the specificity of any effects for metabolic fuels, and because endogenous catecholamines in this site have previously been implicated in corticosterone regulation. In the first experiment adult male albino rats having chronically implanted guide cannulae aimed at the hypothalamic paraventricular nucleus or the caudate nucleus received microinjections of the agonists methoxamine (alpha 1), clonidine (alpha 2), and isoproterenol (beta) (0, 10, 30, 100 nmol/500 nl), and blood samples were taken from the tail tip. In the second experiment a different set of rats received 30 nmol clonidine or vehicle subcutaneously instead of brain microinjections. Intracranial clonidine and isoproterenol produced marked and moderate hyperglycemia, respectively; methoxamine did not alter glucose. For neither clonidine nor isoproterenol was there any difference in hyperglycemia as a function of microinjection site; also, subcutaneous clonidine injections produced the same peak glucose response as was found after both paraventricular and caudate nucleus microinjections of the same dose. Free fatty acid levels were increased by clonidine and isoproterenol, but slightly suppressed by methoxamine; the alpha agonist effects, but not the beta agonist effect, were greater after paraventricular microinjections than after caudate microinjections. Corticosterone was increased by both alpha agonists after paraventricular but not after caudate nucleus microinjections; beta agonist microinjections into the paraventricular and caudate nuclei produced equivalent corticosterone elevations. These results suggest that most, if not all, of the hyperglycemic effects of alpha and beta adrenergic agonist microinjection into the paraventricular nucleus can be ascribed to leakage of the material into the vasculature, with subsequent action at a distant site. In contrast, all 3 agonists seem capable of acting within the brain to alter free fatty acid levels. The effects on corticosterone of both the alpha 1 and alpha 2 agonists, but not the beta agonist, also appear due, at least in part, to actions within the brain. Previous suggestions that catecholamine terminals in the hypothalamic paraventricular nucleus are directly and strongly involved in metabolic fuel regulation may require reconsideration.

Animals↗
PubMed1992

Bombesin-induced hypothermia and hypophagia are associated with plasma metabolic fuel alterations in the rat.

Microinfusion of bombesin into the preoptic area (POA) has previously been shown to reduce core body temperature and feeding in rats that are food-deprived or made hypoglycemic with insulin. The present study determined the metabolic fuel state of rats under these experimental conditions. In addition, changes in plasma metabolic fuels following the microinfusion of bombesin (50 ng/0.25 microliters) into the POA were evaluated. Rats (n = 8) were tested under conditions of food satiation, food deprivation (20 h), and insulin pretreatment (10 U/kg). Prior to peptide infusion, food-deprived rats exhibited the expected elevation in free fatty acids coupled with a small decline in plasma glucose. Insulin treatment resulted in hypoglycemia which persisted for at least 120 min. Following bombesin infusion, free fatty acids and corticosterone levels were elevated in food-sated rats. Food-deprived rats exhibited elevation in plasma glucose, free fatty acids, and corticosterone following peptide infusion. In insulin-treated rats, bombesin attenuated the hypoglycemia observed in controls and increased corticosterone levels. These findings suggest that bombesin-like peptides localized within the POA may participate in the regulation of metabolic fuels.

Animals↗
PubMed1991

mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides.

Four experiments were done to determine which receptor type(s) mediates the effects of third ventricular microinjections of four opioid peptide agonists on blood levels of glucose, free fatty acids, and corticosterone. Tests were performed in unanesthetized adult male albino rats having chronic intraventricular cannulas; blood samples were taken from the tail tip at 0, 15, 30, 60, 90, and 120 min postmicroinjection. In experiment 1, the agonists DAGO (Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol), beta-endorphin, DSLET (d-Ser2-Leu-enkephalin-Thr), and dynorphin A-(1-17) (0, 0.3, 1, 3, and 10 nmol/rat) produced three distinct patterns of changes in serum glucose, free fatty acid, and corticosterone values. Experiment 2 showed that the effects of DAGO and beta-endorphin were inhibited by prior injection with the opiate-receptor blocker naloxone (1 mg/kg sc) and that the effects of dynorphin were not diminished. Experiment 3 determined that dynorphin effects were also not diminished by naloxone given intraventricularly. Experiment 4 found that blockade of the mu-receptor by intraventricular pretreatment with the specific antagonist beta-funaltrexamine (20 micrograms/rat, 24 h before) completely abolished the effects of DAGO and beta-endorphin on glucose and corticosterone. The mu-receptor is critical to the mediation of the hyperglycemia and hypercorticosteronemia induced by the central administration of opiate agonists. These results imply that mu-opioid binding sites previously identified in central autonomic regions may be involved in the regulation of circulating glucose and corticosterone.

Animals↗
PubMed1989

Intracranial microinfusion of pancreastatin elevates blood glucose, free fatty acids, and corticosterone in rats.

Pancreastatin, a novel peptide recently isolated from porcine pancreas, significantly inhibits insulin and somatostatin release and augments glucagon release from the isolated perfused rat pancreas. This implies a role for endogenous pancreatic pancreastatin in the regulation of blood glucose and free fatty acids, the two major metabolic fuels. Since many peptides have similar biological effects when administered centrally and peripherally, the effects of centrally administered pancreastatin on blood glucose and free fatty acids were examined in 3 studies. Corticosterone was also measured in two of these studies. Intraventricular microinfusion of pancreastatin significantly elevated blood glucose, free fatty acid, and corticosterone concentrations in a dose-related manner. None of these effects was seen after subcutaneous injection of the same doses. Centrally administered pancreastatin appears to produce its effects on glucose and free fatty acids through actions in the brain, and either the brain, the median eminence, and/or pituitary for corticosterone.

Animals↗
PubMed1989

Bombesin microinfusion into the rat hypothalamic paraventricular nucleus increases blood glucose, free fatty acids and corticosterone.

Bombesin is a particularly potent hyperglycemic agent when administered intraventricularly or intracisternally in the rat. Because bombesin-like immunoreactivity is found in several forebrain regions implicated in glucoregulation, the ability of direct hypothalamic microinfusions of this peptide to affect serum metabolic fuel levels was tested. Three experiments, using anesthetized, acutely infused rats, or unanesthetized rats with chronic intracranial implants, showed that microinfusion of bombesin into the hypothalamic paraventricular nucleus caused significant, dose-related increases in serum glucose; infusions into the lateral hypothalamus or the caudate nucleus were ineffective. Infusions into the ventromedial nucleus significantly elevated glucose only in acutely anesthetized rats. In unanesthetized rats with chronic intracranial cannulae, bombesin infusions into all 3 hypothalamic sites, but not the caudate-putamen, significantly elevated blood free fatty acids, while only infusions into the paraventricular nucleus caused significant dose-related increases in blood corticosterone. The results demonstrate that the paraventricular nucleus is a sensitive site for bombesin-induced elevation of blood glucose, free fatty acids, and corticosterone. They also imply that the bombesin binding sites and immunoreactive terminals previously identified in these regions may be involved in the central regulation of circulating metabolic fuel levels and the pituitary-adrenal axis, and that the effects of acute surgery may augment the hyperglycemic response to intrahypothalamic bombesin administration.

Animals↗
PubMed1989

Age-related changes in the motor response to environmental novelty in the rat.

To examine age-related changes in responsiveness to environmental novelty, 3-, 12-, and 24-month-old male Fischer 344 rats were maintained on a restricted diet and exposed to a modified open field for 10 min on each of 10 consecutive days. On the first day of testing, animals of all groups showed equal amounts of rearing. While the 3-month animals continued to show approximately the same levels of rearing until the 8th day, by day 5, the older groups (12- and 24-month) had significantly reduced their rearing. Conversely, grooming was initially highest among the 24-month-old animals. While 3- and 12-month rats showed habituation of grooming, the oldest animals failed to habituate their grooming response by day 5. By day 10, there were no significant differences among the groups in either rearing or grooming. Although food was available in the center of the modified open field, there was little eating and there were no differences among groups. However, all animals did eat quickly when food was made available in their home cages. Thus, all animals displayed a profile of stress-related responses to open field exposure. Plasma corticosterone levels likewise were elevated in the modified open field. Some, but not all, components of this response profile habituated over the 10 days of exposure. Three-month-old animals responded to the novelty predominantly by rearing and 24-month animals predominantly by grooming. This suggests that with aging, locomotor responses to stress are replaced by a more self-directed form of displacement activity.

Aging↗
PubMed1989

Absence of the dawn glucose rise in nondiabetic men compared by age.

To determine whether the dawn phenomenon occurs in healthy elderly subjects, we compared glucose and insulin levels as well as glucose production rates in 10 young nondiabetic men (mean age 26 +/- 3 years) and 10 old nondiabetic men (mean age 69 +/- 3 years) between 0500 to 0800. Young subjects demonstrated a modest but significant rise in plasma glucose level (89 +/- 1 mg/dl to 92 +/- 1 mg/dl, p less than .05) and glucose production rate (1.7 +/- 0.1 mg/kg/min to 1.9 +/- 0.2 mg/kg/min, p less than .05) between 0540 and 0800. No rise was detected in the plasma glucose or glucose production rate in older subjects as a group, between these times. However, a few elderly subjects did display a dawn glucose rise. Changes in plasma insulin levels were not significant for either young or old subjects. Older subjects had significantly lower mean peak growth hormone levels during the night than young subjects (6.7 +/- 1.3 vs 10.1 +/- 1.6 ng/ml, p less than .05). These results demonstrate a modest rise in plasma glucose levels and glucose production rate in healthy young subjects consistent with previous reports of the dawn phenomenon. This modest early morning glucose rise is absent in most otherwise healthy older subjects.

Adult↗