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Biomedical subjects

M C Moore

Publications and source records attributed to M C Moore.

At least 19 recordsLinked to original sources
PubMed2005

Voluntary exercise delays monogenetic obesity and overcomes reproductive dysfunction of the melanocortin-4 receptor knockout mouse.

The melanocortin system is involved in hypothalamic regulation of energy homeostasis. The melanocortin-4 receptor (MC4R) has been linked to both obesity and reproductive dysfunction. Deletion of the MC4R from the mouse genome has resulted in phenotypes including adult onset obesity, hyperphagia, and difficulty in reproducing when homozygote parents are bred. Additionally, polymorphisms of the human MC4R have been identified in morbidly obese children and adults. Herein, we have identified that voluntary exercise, provided via the presence of a running wheel, impedes the monogenetic obesity (at 20 weeks of age running wheel housed body weight=31+/-1.8 g versus conventionally housed body weight=41+/-2.3 g, a 25% decrease in body weight p<0.01), hyperphagia (average cumulative food intake is not statistically different than wild type mice housed in running wheel cages), and reproductive dysfunction phenotypes associated with the MC4R knockout mice housed by conventional means. These data demonstrate the novel finding that voluntary exercise at a young age may hinder genetically induced obesity.

Age Factors↗
PubMed2005

Modified melanocortin tetrapeptide Ac-His-dPhe-Arg-Trp-NH at the arginine side chain with ureas and thioureas.

The Ac-His-dPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.

Animals↗
PubMed2004

Insulin-independent effects of GLP-1 on canine liver glucose metabolism: duration of infusion and involvement of hepatoportal region.

UNLABELLED: Whether glucagon-like peptide-1 (GLP-1) has insulin-independent effects on glucose disposal in vivo was assessed in conscious dogs by use of tracer and arteriovenous difference techniques. After a basal period, each experiment consisted of three periods (P1, P2, P3) during which somatostatin, glucagon, insulin, and glucose were infused. The control group (C) received saline in P1, P2, and P3, the PePe group received saline in P1 and GLP-1 (7.5 pmol.kg(-1).min(-1)) peripherally (Pe; iv) in P2 and P3, and the PePo group received saline in P1 and GLP-1 peripherally (iv) (P2) and then into the portal vein (Po; P3). Glucose and insulin concentrations increased to two- and fourfold basal, respectively, and glucagon remained basal. GLP-1 levels increased similarly in the PePe and PePo groups during P2 ( approximately 200 pM), whereas portal GLP-1 levels were significantly increased (3-fold) in PePo vs. PePe during P3. In all groups, net hepatic glucose uptake (NHGU) occurred during P1. During P2, NHGU increased slightly but not significantly in all groups. During P3, NHGU increased in PePe and PePo groups to a greater extent than in C, but no significant effect of the route of infusion of GLP-1 was demonstrated (16.61 +/- 2.91 and 14.67 +/- 2.09 vs. 4.22 +/- 1.57 micromol.kg(-1).min(-1), respectively). IN CONCLUSION: GLP-1 increased glucose disposal in the liver independently of insulin secretion; its full action required long-term infusion. The route of infusion did not modify the hepatic response.

Animals↗
PubMed2004

Activation of aggressive behavior by progesterone and testosterone in male tree lizards, Urosaurus ornatus.

Testosterone is usually thought to be the major sex steroid regulating adult male territorial aggression in vertebrates. However, recent evidence has suggested a role for progesterone, as well as testosterone, in the organization of the two male reproductive phenotypes of tree lizards (Urosaurus ornatus), which differ in adult levels of territorial behavior. In the present experiment we tested whether progesterone and testosterone could also play an activational role in the expression of adult aggressive behavior. We subjected post-reproductive male tree lizards to the following treatments: sham surgery, castration, castration with progesterone supplementation, and castration with testosterone supplementation. We measured several different dimensions of aggressive behavior. Overall in these post-reproductive animals, the level of aggression from lowest to highest was: castrates, shams, progesterone-treated, and testosterone-treated. Although testosterone appears to be the more potent regulator of aggressive behavior, progesterone enhanced several measures of aggression suggesting that it could play a role in natural regulation of aggressive behavior. This initial study used very high levels of progesterone (similar to or above those experienced by hatchlings) to maximize the probability of detecting an effect. Further studies are needed to determine if natural adult progesterone levels are sufficiently high to influence aggressive behavior.

Aggression↗
PubMed2003

Temporal patterns of limbic monoamine and plasma corticosterone response during social stress.

Dominant and subordinate males respond differently to the stress of social interaction. After an hour of social interaction, subordinate male Anolis carolinensis have elevated serotonergic activity in hippocampus, but dominant males do not. In other species, and using other stressors, the activation of hippocampal serotonergic activity is much more rapid than one hour. To elucidate early stress responsiveness, adult male A. carolinensis were divided into four groups: isolated controls, and pairs of males sampled after 10, 20 or 40 minutes of aggressive interaction. Development of dominant-subordinate relationships was determined by behavior and by the celerity of eyespot darkening. Serotonergic activity in the hippocampus, nucleus accumbens and amygdala was elevated rapidly and equally in both dominant and subordinate males, as were plasma corticosterone concentrations. Serotonergic activity remained elevated through 40 minutes in hippocampus and nucleus accumbens. Only subordinate males had elevated corticosterone levels at 40 minutes. Social status does not impede socially induced stress responses. Rather, rapid regulation of serotonergic stress responses appears to be a mediating factor in determining both behavioral output and social status. Temporal expressions of monoaminergic and endocrine stress responses are distinctive between males of dominant and subordinate social status. Such temporal patterns of transmitter and glucocorticoid activity may reflect neurocircuitry adaptations that result in behavior modified to fit social status.

Aggression↗
PubMed2002

Effect of captivity in semi-natural enclosures on the reproductive endocrinology of female lizards.

Long-term captivity can result in abnormal behavior and physiology in many vertebrates. Here, we examine whether semi-natural, outdoor captive environments can offer a compromise, allowing much of the experimental control afforded by captivity, while providing the environmental conditions essential for normal behavior and physiology. We first determined plasma concentration of the sex steroid hormones progesterone, testosterone, and estradiol of free-ranging female striped plateau lizards (Sceloporus virgatus) throughout the reproductive season, and second, compared the results to those from conspecific females maintained in semi-natural outdoor enclosures. Among free-ranging females, levels of progesterone and estradiol were elevated during vitellogenesis, with an apparent surge in progesterone and testosterone occurring in association with ovulation. Following ovulation, estradiol fell to non-reproductive levels while progesterone remained elevated during the month-long period of gravidity. Long-term captivity in outdoor enclosures did not significantly affect progesterone or estradiol levels at any stage of the reproductive cycle, and did not affect testosterone levels during normal ovarian development and gravidity. However, (1) females with delayed oviposition in captivity had lower testosterone levels than free-ranging females with normal oviposition, and (2) when all females sampled were post-reproductive, captive females continued to have lower testosterone levels than free-ranging females. Thus, the endocrine response to captivity may be greater among post-reproductive females than among reproductive females. Our results are in marked contrast to many studies that show captivity can dramatically impair reproduction of female vertebrates.

Animals↗
PubMed2001

Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes.

OBJECTIVE: In normal adults, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to a glucose load, especially in those with the poorest glucose tolerance. We hypothesized that an acute catalytic dose of fructose would also improve glucose tolerance in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Five adults with type 2 diabetes underwent an oral glucose tolerance test (OGTT) on two separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without the addition of 7.5 g fructose (OGTT + F or OGTT - F), in random order. Arterialized blood samples were collected from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 3 h afterward. RESULTS: The area under the curve (AUC) of the plasma glucose response was reduced by fructose administration in all subjects; the mean AUC during the OGTT + F was 14% less than that during the OGTT - F (P < 0.05). The insulin AUC was decreased 21% with fructose administration (P = 0.2). Plasma glucagon concentrations declined similarly during OGTT - F and OGTT + F. The incremental AUC of the blood lactate response during the OGTT - F was approximately 50% of that observed during the OGTT + F (P < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTTs. CONCLUSIONS: Low-dose fructose improves the glycemic response to an oral glucose load in adults with type 2 diabetes, and this effect is not a result of stimulation of insulin secretion.

Adult↗
PubMed2000

Discrimination in resolving systems. V. Pseudoephedrine - fluoromandelic acid diastereomers.

Resolution of the isomeric 2'-, 3'-, and 4'-fluoromandelic acids with (+)-(1S;2S)-pseudoephedrine in 95% ethanol produces both well and poorly discriminating, hydrated and unsolvated binary salts. Seven observed diastereomeric phases are represented by five crystal structure types including three of the four types observed in the pseudoephedrine mandelates. Type a: monoclinic hemihydrate less-soluble (L) (R)-3'-fluoromandelate and more-soluble (M) (R)-4'-fluoromandelate (I); type b: orthorhombic unsolvated M (S)-2'-fluoromandelate; type c: orthorhombic unsolvated L (R)-2'-fluoromandelate; type d: orthorhombic dihydrate M (S)-3'-fluoromandelate and L (S)-4'-fluoromandelate; type e: monoclinic unsolvated M (R)-4'-fluoromandelate (II). Largest (15-fold) discriminating solubilities in 95% ethanol are found between the diastereomers with 2'-fluoromandelic acid, 50% more than in the corresponding ephedrine system. Principle interionic interactions are hydrogen-bonds between protonated secondary ammonium ions and carboxylates. Infinite chains of these are found in type c, with a four-atom repeating unit H-N(+)-H.O(-C(-)-O) [C(2)(1)(4)], and in types b and d, with a six-atom repeating unit H-N(+)-H.O-C(-)-O [C(2)(2)(6)]. Water of crystallization intervenes in the chains of type a but not of type d hydrated salts, according with higher average dehydration temperatures in the former. Hydrated salts in general are excessively soluble in 95% ethanol.

Ephedrine↗
PubMed2000

Pharmacological adrenalectomy with mitotane.

The potential of mitotane (ortho, para'-DDD, commonly used to treat adrenal carcinomas in humans and dogs) was investigated as an alternative to surgical adrenalectomy in birds, salamanders, and lizards. House sparrows (Passer domesticus) were injected twice daily with vehicle or one of two doses of mitotane (225 or 450 mg/kg), and basal and stress-induced levels of corticosterone (CORT) were measured 3 and 5 days after injections. Mitotane reduced basal CORT levels to nondetectable and abolished stress-induced CORT increases by the 3rd day of treatment. In another study, a single injection of mitotane was effective in lowering endogenous CORT levels 36 h later, but levels had apparently recovered by 10 days after the injection. Mitotane did not effect testicular weights and had no detectable effect on testosterone levels. In contrast to its effects on house sparrows, mitotane did not lower endogenous CORT levels in either tiger salamanders (Ambystoma tigrinum) or tree lizards (Urosaurus ornatus), even at doses much higher than those used in house sparrows.

Adrenalectomy↗
PubMed2000

Plasma steroid-binding globulin mediation of differences in stress reactivity in alternative male phenotypes in tree lizards, Urosaurus ornatus.

Plasma steroid-binding globulins, for example, corticosteroid-binding globulin and sex hormone-binding globulin (SHBG), have been identified in a number of vertebrates. One possible function of these proteins is to regulate the amount of steroid delivery to target tissues, as only free steroids are believed to diffuse from the circulation to target cells. Male tree lizards, Urosaurus ornatus, exhibit alternative male reproductive tactics correlated with dewlap (throat-fan) coloration. Males with orange-blue dewlaps are aggressive and territorial, whereas males with orange dewlaps are less aggressive and employ a satellite strategy. The two types of males have similar basal levels of total plasma corticosterone and testosterone. However, testosterone levels of nonterritorial males are more sensitive than those of territorial males to negative regulation by stress-induced increases in corticosterone. We tested the hypothesis that this difference in corticosterone feedback on testosterone could be mediated, in part, by differences in binding globulin levels between the two types of males. We have identified two steroid-binding globulins in male tree lizards. The first binds androgens and estradiol with high affinity (10(-9) M) and is similar to previously described sex hormone-binding globulins. The second binds both androgens and C(21) steroids, such as progesterone and corticosterone, with higher specificity than estradiol and is best described as an androgen-glucocorticoid-binding globulin (AGBG). In both types of males, the capacity of AGBG is much higher than SHBG. In addition, AGBG capacity is significantly greater in territorial than nonterritorial males, whereas the capacity of SHBG does not differ between the two types of males. Calculations of free steroid levels based on the affinity and capacity measures suggest that although most testosterone circulates bound to binding globulins, binding capacity is high enough that binding globulins are also able to bind to other steroids such as corticosterone. Thus, differences in binding capacity between the two types of males could result in higher levels of free corticosterone in nonterritorial males than in territorial males, especially during stress-induced increases in corticosterone, and may explain why testosterone levels of nonterritorial males are more sensitive to negative feedback by corticosterone.

Aggression↗
PubMed2000

Importance of the hepatic arterial glucose level in generation of the portal signal in conscious dogs.

The aim of this study was to determine whether the elimination of the hepatic arterial-portal (A-P) venous glucose gradient would alter the effects of portal glucose delivery on hepatic or peripheral glucose uptake. Three groups of 42-h-fasted conscious dogs (n = 7/group) were studied. After a 40-min basal period, somatostatin was infused peripherally along with intraportal insulin (7.2 pmol x kg(-1) x min(-1)) and glucagon (0.65 ng x kg(-1) x min(-1)). In test period 1 (90 min), glucose was infused into a peripheral vein to double the hepatic glucose load (HGL) in all groups. In test period 2 (90 min) of the control group (CONT), saline was infused intraportally; in the other two groups, glucose was infused intraportally (22.2 micromol x kg(-1) x min(-1)). In the second group (PD), saline was simultaneously infused into the hepatic artery; in the third group (PD+HAD), glucose was infused into the hepatic artery to eliminate the negative hepatic A-P glucose gradient. HGL was twofold basal in each test period. Net hepatic glucose uptake (NHGU) was 10.1 +/- 2.2 and 12.8 +/- 2.1 vs. 11.5 +/- 1.6 and 23.8 +/- 3.3* vs. 9.0 +/- 2.4 and 13.8 +/- 4.2 micromol x kg(-1) x min(-1) in the two periods of CONT, PD, and PD+HAD, respectively (* P < 0.05 vs. same test period in PD and PD+HAD). NHGU was 28.9 +/- 1.2 and 39.5 +/- 4.3 vs. 26.3 +/- 3.7 and 24.5 +/- 3.7* vs. 36.1 +/- 3.8 and 53.3 +/- 8.5 micromol x kg(-1) x min(-1) in the first and second periods of CONT, PD, and PD+HAD, respectively (* P < 0.05 vs. same test period in PD and PD+HAD). Thus the increment in NHGU and decrement in extrahepatic glucose uptake caused by the portal signal were significantly reduced by hepatic arterial glucose infusion. These results suggest that the hepatic arterial glucose level plays an important role in generation of the effect of portal glucose delivery on glucose uptake by liver and muscle.

Animals↗
PubMed2000

Nonhepatic response to portal glucose delivery in conscious dogs.

The glycemic and hormonal responses and net hepatic and nonhepatic glucose uptakes were quantified in conscious 42-h-fasted dogs during a 180-min infusion of glucose at 10 mg. kg(-1). min(-1) via a peripheral (Pe10, n = 5) or the portal (Po10, n = 6) vein. Arterial plasma insulin concentrations were not different during the glucose infusion in Pe10 and Po10 (37 +/- 6 and 43 +/- 12 microU/ml, respectively), and glucagon concentrations declined similarly throughout the two studies. Arterial blood glucose concentrations during glucose infusion were not different between groups (125 +/- 13 and 120 +/- 6 mg/dl in Pe10 and Po10, respectively). Portal glucose delivery made the hepatic glucose load significantly greater (36 +/- 3 vs. 46 +/- 5 mg. kg(-1). min(-1) in Pe10 vs. Po10, respectively, P < 0.05). Net hepatic glucose uptake (NHGU; 1.1 +/- 0. 4 vs. 3.1 +/- 0.4 mg. kg(-1). min(-1)) and fractional extraction (0. 03 +/- 0.01 vs. 0.07 +/- 0.01) were smaller (P < 0.05) in Pe10 than in Po10. Nonhepatic (primarily muscle) glucose uptake was correspondingly increased in Pe10 compared with Po10 (8.9 +/- 0.4 vs. 6.9 +/- 0.4 mg. kg(-1). min(-1), P < 0.05). Approximately one-half of the difference in NHGU between groups could be accounted for by the difference in hepatic glucose load, with the remainder attributable to the effect of the portal signal itself. Even in the absence of somatostatin and fixed hormone concentrations, the portal signal acts to alter partitioning of a glucose load among the tissues, stimulating NHGU and reducing peripheral glucose uptake.

Animals↗
PubMed2000

Estradiol modulation of central monoamine activity in female mountain spiny lizards.

Although estradiol (E2) mediates many behaviors in females, relatively little is known about its role in female aggression. Previous studies in female mountain spiny lizards indicated that female aggression is modulated by ovariectomy and sex steroid hormone replacement and that expression of aggressive behavior is accompanied by changes in serotonin activity. This study examines if E2 modulates the activity of serotonin and other central monoamines. Free-living females were caught and housed in the laboratory and received one of 3 treatments: sham surgery (SHAM), ovariectomy plus empty implant (OVEX), or sham surgery plus a long lasting E2 implant (E2-IMP). After 3 weeks of treatment, selected brain areas were examined for levels of monoamines and their metabolites. Changes in monoamine activity were most pronounced in the septum where levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine (NE) were higher in E2-IMP females relative to SHAM, and levels of 5-HIAA were higher in OVEX females relative to SHAM. Changes in dopamine (DA) activity were also found, with increased DA concentration and decreased ratio of forebrain:brainstem HVA concentrations in E2-IMP relative to SHAM females. These results suggest that the actions of E2 on aggression might be mediated, in part, by dose-dependent effects on 5-HT activity in the septum.

Aggression↗
PubMed2000

Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults.

In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load. Therefore, we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers (5 men and 6 women). Each subject underwent an oral glucose tolerance test (OGTT) on 2 separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without 7.5 g fructose (OGTT+F or OGTT-F), in random order. Arterialized blood samples were obtained from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward. The area under the curve (AUC) of the change in plasma glucose was 19% less in OGTT+F vs. OGTT-F (P: < 0.05). Glucose tolerance was improved by fructose in 9 subjects and worsened in 2. All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F (31 +/- 5% decrease). The insulin AUC did not differ between the 2 studies. Of the 9 subjects with improved glucose tolerance during the OGTT+F, 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50% greater during the OGTT+F (P: < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTT. In conclusion, low dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.

Adult↗
PubMed1999

Ovarian hormones influence territorial aggression in free-living female mountain spiny lizards.

Females are aggressive in many species but relatively little is known about the hormonal basis of female aggression, especially in free-living animals. Female mountain spiny lizards aggressively defend territories from other females. Previously, we showed that plasma levels of testosterone (T) and estradiol (E) are positively associated with levels of female aggression. Here, we manipulated hormone levels in free-living females and examined aggression expressed by females returned to their natural territories. Females received one of the following: (1) ovariectomy + empty implant (OVEX), (2) ovariectomy + T implant (T-IMP), or (3) sham surgery + empty implant (SHAM). OVEX females had reduced plasma levels of E but not T relative to SHAM females. T-IMP females had elevated plasma levels of T. Levels of display and aggression in OVEX females were reduced relative to SHAM females. T-IMP females had restored levels of display behavior although, unlike SHAM, no T-IMP females expressed the overt aggressive behavior of charging. These data are most consistent with the hypothesis that an ovarian factor such as E promotes female aggression, since ovariectomy reduced both plasma E and aggression but had no effect on plasma T. The results from the T-IMP females are also consistent with this hypothesis if we assume that the effects of T are due to aromatization to E in target tissues. The data do not rule out a role for T in promoting female aggression since T-implants resulted in elevated plasma T and restored display behaviors. This study represents one of the first studies examining the hormonal basis of female aggression in free-living females.

Aggression↗