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N Geary

Publications and source records attributed to N Geary.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Pancreatic glucagon: physiological signal of postprandial satiety].

Pancreatic glucagon, in addition to its metabolic effects, appears to accelerate postprandial satiety which controls meal size. Glucagon is released during meals. Administration of glucagon at the beginning of meals reduces the size of test meals in animals and humans, and reduces the size of spontaneous meals in rats. This effect is behaviorally indistinguishable from normal satiety in rats and subjectively indistinguishable from normal satiety in humans. Antagonism of the action of endogenous glucagon during meals by administration of glucagon antibodies increases both test meals and spontaneous meals. These results indicate that glucagon is a physiological satiety signal. The possible mechanisms through which glucagon's effect is transduced into a neural signal and relayed to the brain are also reviewed. Finally, we discuss the possible, but not yet clear, role of glucagon in obesity, and as a potential therapeutic tool for the treatment of eating disorders.

Animals↗
PubMed1992

Cocaine decreases self-control in rats: a preliminary report.

Cocaine abuse is often associated with behavior that takes into account short-term, but not long-term consequences. However, there has been no empirical research concerning the effects of cocaine on self-control (choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer). In the present research, when food-deprived rats repeatedly chose between a larger, more delayed food reinforcer and a smaller, less delayed food reinforcer, chronic intraperitoneal injections of 15 mg/kg cocaine (but not 10 mg/kg fluoxetine) decreased the rats' choices of the larger, more delayed reinforcer. Cocaine can decrease rats' self-control.

Animals↗
PubMed1992

Scheduled running wheel activity indexes the specificity of pharmacological anorexia.

Nondeprived male Sprague-Dawley rats that were given scheduled access to running wheels for 60 min daily ran immediately and energetically. Intraperitoneal injections of 400 micrograms/kg pancreatic glucagon and 0.15 microgram/kg cholecystokinin octapeptide had no effect on scheduled running, but significantly inhibited feeding when the rats were offered condensed milk instead of access to the running wheels. This is consistent with the hypothesized function of these peptides as postprandial satiety signals. In contrast, 0.5 mg/kg amphetamine and 75 microM/kg LiCl, which produced similar degrees of anorexia, inhibited running by about 50%. Amphetamine, but neither peptide, also inhibited water drinking and disrupted the behavioral sequence of postprandial satiety. The distance run during scheduled running tests was inversely related to body weight, but the patterns of the drugs' effects were not altered by baseline running differences. Scheduled wheel running is a robust consummatory behavior that appears to provide a relatively valid, simple, and sensitive test of the behavioral specificity of pharmacological anorexia.

Amphetamine↗
PubMed1992

Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men.

Pancreatic glucagon and cholecystokinin octapeptide (CCK-8) were intravenously infused (1 ml/min for 10 min) alone or in combination beginning 15 min after normal-weight men had eaten a 500-ml tomato soup preload and 5 min before they were served a lunch of macaroni and beef with tomato sauce. Infusion of approximately 3 ng.kg-1.min-1 glucagon or approximately 2 ng.kg-1.min-1 CCK-8 each reduced test meal size. However, simultaneous infusion of these peptide doses reduced meal size less than the sum of the peptides' individual effects. Infusions of approximately 1.5 ng.kg-1.min-1 glucagon or approximately 1 ng.kg-1.min-1 CCK-8 had neither individual nor interactive effects on meal size. Psychophysical ratings failed to detect nonspecific side effects after any of the infusions. That exogenous glucagon and CCK-8 each reduced meal size without side effects suggests that these peptides may participate in the physiological control of human appetite; that their simultaneous infusion resulted in an infra-additive reduction in meal size suggests that they can interact antagonistically.

Adolescent↗
PubMed1991

Intraperitoneal injections of nanogram CCK-8 doses inhibit feeding in rats.

The satiating effect of intraperitoneal injections of synthetic cholecystokinin octapeptide (CCK-8) was tested in non-deprived and 17 h-deprived male and female Sprague-Dawley rats that were maintained on pelleted diet and offered evaporated milk test meals. At the midpoint of the 12-h diurnal period, 40-160 ng/kg CCK-8 elicited a dose-related decrease in meal size. At midnight, CCK-8's threshold for inhibiting feeding was increased to 80-160 ng/kg in nondeprived and deprived rats, respectively. These doses are 25-50 times less than typically required to significantly decrease food intake after intraperitoneal injection. No CCK-8 dose stimulated nocturnal feeding and no consistent sex difference was observed in CCK-8's effect. Intraperitoneal injection of ng amounts of CCK-8 may mimic a paracrine action of endogenous gut cholecystokinin to signal satiety.

Animals↗
PubMed1991

Hepatic portal glucagon infusion decreases spontaneous meal size in rats.

We describe the first tests of intraportal pancreatic glucagon infusions during spontaneous meals in undisturbed, ad libitum-fed male Sprague-Dawley rats. Two-minute infusions beginning at meal onset and delivering 14 micrograms glucagon reduced the size and duration of both early and late nocturnal meals. After glucagon infusion during early nocturnal meals, neither the latency nor the size of the next meal was affected. Meal onset infusion of 3.4-14 micrograms glucagon/meal dose-dependently reduced late nocturnal meal size 19-64%. Full-meal glucagon infusions did not inhibit feeding more than 2-min infusions begun at meal onset or meal middle, despite fivefold differences in amount infused. These data indicate that spontaneous feeding is pharmacologically inhibited by prandial changes in hepatic portal glucagon concentration.

Animals↗
PubMed1991

Hepatic portal infusion of glucagon antibodies increases spontaneous meal size in rats.

Specific antibodies to pancreatic glucagon in a dose sufficient to neutralize 1.5 ng glucagon in vitro were intraportally infused during the first 2 min of spontaneous meals in ad libitum-fed male Sprague-Dawley rats. In separate tests, glucagon antibodies stimulated feeding during the first spontaneous meal of the dark phase (73% mean increase in meal size) and during spontaneous meals in the last quarter of the dark phase (58% increase). These results indicate that a glucagon-sensitive satiety mechanism has a physiological role in the control of nocturnal feeding in rats.

Animals↗
PubMed1990

2-Mercaptoacetate stimulates sham feeding in rats.

Rats maintained on a LF diet (Purina chow) were pretreated with 0.3 M/kg 2-mercaptoacetate, an antagonist of B-oxidation of fatty acids, 60 min before sham feeding condensed milk with open gastric cannulas. 2-Mercaptoacetate significantly increased 30-min milk intake by about 35%. This suggests that blockade of fatty acid oxidation 1) participates control of feeding even in rats adapted to low fat diets, and 2) modulates not only the timing of meal initiation as previously reported by others, but also may influence the rate of ingestion and/or meal size. Finally, 2-mercaptoacetate pretreatment did not block the synergistic inhibition of sham feeding elicited by simultaneous injections of glucagon and cholecystokinin.

Animals↗
PubMed1990

Redundant vagal mediation of the synergistic satiety effect of pancreatic glucagon and cholecystokinin in sham feeding rats.

Simultaneous intraperitoneal injection of pancreatic glucagon (PG) and cholecystokinin (CCK) results in a functionally synergistic satiety effect in non-deprived sham feeding rats ("PG-CCK satiety"). That is, PG and CCK together inhibit feeding significantly more than the sum of their individual effects. Because the individual satiety effect of each peptide on normal feeding is dependent on the abdominal vagus nerve, we tested the vagal mediation of this synergistic effect of PG plus CCK. Vagotomies were verified anatomically and, in one experiment, histologically. Total abdominal vagotomy blocked PG-CCK satiety. Neither selective vagotomies of the hepatic, the gastric, the celiac, the gastric and celiac, nor the gastric and hepatic branches, however, affected PG-CCK satiety. This indicates that the vagal contribution to the synergistic satiety effect of PG plus CCK on sham feeding is redundant. Although some vagal fibers are necessary for PG-CCK satiety, no individual branch is required for the effect, and at least two branches, the hepatic and celiac, are each sufficient for mediating it.

Animals↗
PubMed1990

Pancreatic glucagon signals postprandial satiety.

The hypothesis that prandial increases in circulating pancreatic glucagon initiates an important peripheral satiety signal is reviewed. Glucagon administration at the beginning of meals reduces the size of test meals in animals and humans and reduces the size of spontaneous meals in rats. Exogenous glucagon may also interact synergistically with cholecystokinin to inhibit feeding. These appear to be satiety effects because they are behaviorally specific in rats and subjectively specific in humans. Glucagon's pharmacological satiety effect is complemented by compelling evidence for a necessary contribution of endogenous glucagon to the control of meal size: administration of glucagon antibodies increases both test and spontaneous meal size in rats. Under many, but not all, conditions exogenous glucagon's satiety effect appears to originate in the liver and to be relayed to the brain via hepatic vagal afferents. Analysis of the central processing of this signal, however, has barely begun. How glucagon changes are transduced into neural afferent signals also remains an open question. The only hypothesis that has been extensively tested is that stimulation of hepatic glucose production initiates the satiety signal, but this is neither convincingly supported nor clearly rejected by currently available data. It is also not yet clear whether glucagon contributes to some forms of obesity or has potential use as a therapeutic tool in the control of eating disorders. Of the several proposed controls of hunger and satiety, glucagon appears to be one of the most likely to be physiologically relevant. This encourages further analysis of its behavioral characteristics, its neural mechanisms, and its clinical potential.

Animals↗
PubMed1989

Pancreatic glucagon does not alter intrameal gastric emptying of milk in the rat.

The hypothesis that pancreatic glucagon (PG) inhibits feeding by altering intrameal gastric emptying was tested in nondeprived rats at midday, conditions under which exogenous PG is thought to elicit satiety. Rats received intraperitoneal injections of PG (400 or 800 micrograms/kg), cholecystokinin (CCK, 0.5 or 1.0 micrograms/kg) or saline and were given bolus intragastric infusions of 10 ml evaporated milk through chronic gastric cannulae. PG did not affect volumes of stomach contents recovered 20 minutes postinjection. In contrast, CCK inhibited gastric emptying in a dose-related manner. When milk was offered to the same rats to drink, 400 micrograms/kg PG significantly reduced meal size. These findings suggest that PG's satiety effect is not caused by its effect on stomach emptying.

Animals↗
PubMed1989

Phenylpropanolamine and amphetamine disrupt postprandial satiety in rats.

Two tests of the behavioral specificity of the anorectic effects of amphetamine (AM) and phenylpropanolamine (PPA) were done. Intraperitoneal injections of each drug reduced the size of condensed milk test meals in 30-min pellet-deprived rats. The dose-response relations in semi-log coordinates were linear and parallel, but AM (ED50, 2.0 +/- 0.1 mumol/kg) was about ten times more potent than PPA (ED50, 24.6 +/- 0.1 mumol/kg). Periprandial behaviors were observed using a time-sampling technique. Both AM and PPA disrupted the normal behavioral sequence of postprandial satiety throughout their anorectic ranges, but they did so differently. AM increased postprandial exploratory behavior, decreased or eliminated resting, and, at larger doses, elicited stereotypy. In contrast, PPA inhibited both grooming and exploration, and increased resting. The drugs' effects on water intake were tested in 17-hr water-deprived rats. AM's adipsic effect (ED50, 2.3 +/- 0.1 mumol/kg) was similar to its anorectic effect. PPA also inhibited drinking, although slightly less potently (ED50, 56.6 +/- 0.1 mumol/kg) than it did feeding. Thus, under conditions maximizing the anorectic potencies of systemically administered AM and PPA in rats, both drugs inhibited feeding nonspecifically rather than by eliciting normal postprandial satiety.

Amphetamine↗
PubMed1988

CCK inhibits real and sham feeding in gastric vagotomized rats.

We tested both sham feeding and real feeding in gastric vagotomized rats equipped with chronic gastric cannulas, either without pretest food deprivation or after 18 hr food deprivation. In each condition, 0.3-4 micrograms/kg CCK inhibited food intake similarly in control and vagotomized rats. Behavioral observations indicated the presence of normal postprandial satiety after CCK. We then tested real feeding in noncannulated rats after either total abdominal vagotomy, gastric vagotomy, or control operation. Doses of 0.5-4 micrograms/kg CCK had no effect on food intake after total vagotomy, but again inhibited feeding with equal potency in gastric vagotomized and control rats. The inhibitory effect of 6 micrograms/kg CCK was attenuated but not blocked by total vagotomy. Finally, we tested rats with gastric cannulas after gastric plus celiac vagotomy. CCK also inhibited both real and sham feeding after this lesion. These data confirm previous findings that abdominal vagal fibers mediate the satiety effect of moderate intraperitoneal doses of CCK, but fail to support the hypothesis that gastric branch fibers are the necessary vagal contribution.

Animals↗
PubMed1987

Epinephrine inhibits feeding nonspecifically in the rat.

The hypothesis that epinephrine (EPI) and pancreatic glucagon (PG) inhibit feeding by activating a common physiological satiety mechanism was tested by comparing the two agents' behavioral effects. In several tests of specificity, EPI and PG had functionally different inhibitory actions. Intraperitoneal injection of 6.25-50 micrograms/kg EPI and 100-400 micrograms/kg PG elicited overlapping dose-related inhibitions of intake of milk diet in rats maintained ad lib on pelleted chow. Twenty-five to 50 micrograms/kg EPI also elicited anomalous behaviors that are not normally associated with feeding, including supine postures with limbs extended and crawling with trunk dorsoflexed and abdomen pressed against cage floor. EPI elicited similar anomalous behaviors in rats that either sham fed with open gastric cannulas, drank after water deprivation, or were presented neither food nor water. Fifty to 200 micrograms/kg EPI also inhibited water intake in the thirsty rats, and 25-50 micrograms/kg EPI inhibited sham feeding. PG, in contrast, neither elicited anomalous behaviors nor inhibited water intake nor inhibited sham feeding. These data demonstrate that the inhibitory actions of exogenous EPI and PG are functionally dissociable. We conclude that 25-200 micrograms/kg EPI acts nonspecifically to produce anorexia and adipsia, while PG elicits postprandial satiety.

Animals↗
PubMed1987

Food deprivation dissociates pancreatic glucagon's effects on satiety and hepatic glucose production at dark onset.

We compared the effects of different durations of pretest food deprivation on pancreatic glucagon's (PG) satiating and glycogenolytic actions in order to test the hypothesis that stimulation of hepatic glucose production causes PG's satiety effect. Rats were maintained on a 12:12 LD cycle (lights off: 1015) and deprived of food 45 min or 8, 12, 18, or 24 hr before intraperitoneal injection of 400 micrograms/kg PG. Testing began at 1015, the beginning of the dark phase. Food intake was not inhibited after 45 min of pretest food deprivation (30 min change, 2.5 +/- 4.0%, p greater than 0.05), but was inhibited after 8 or more hr food deprivation. The largest inhibitory effect, 16.2 +/- 3.8%, p less than 0.01, occurred after 8 hr food deprivation. In separate experiments, rats were food deprived 45 min or 8 hr, similarly injected, and killed 10 min after refeeding for blood and liver samples. Hepatic glycogen content at meal onset was higher in rats deprived 45 min than in rats deprived 8 hr (3.2 +/- 0.3 vs. 1.7 +/- 0.3% liver weight, p less than 0.01), and PG injection produced a higher level of hepatic vein blood glucose in the less deprived rats (196 +/- 5 vs. 168 +/- 12 mg/dl, p less than 0.05). Thus, in rats tested at the beginning of the dark phase of the LD cycle after 45 min or 8 hr food deprivation, there is an inverse relation between PG's potencies to inhibit food intake and to stimulate hepatic glucose production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Pancreatic glucagon and cholecystokinin synergistically inhibit sham feeding in rats.

Pancreatic glucagon (PG) elicits satiety in normally feeding rats but fails to inhibit sham feeding in rats with open gastric cannulas. This suggests that a gastric or postgastric food stimulus is necessary for PG's satiating action. To determine whether bombesin or cholecystokinin might provide such a stimulus, sham-feeding rats received simultaneous intraperitoneal injections of 100-800 micrograms/kg of PG and doses of bombesin or cholecystokinin (CCK) that were near the threshold for inhibition of sham feeding. PG and 0.15-to 0.30-micrograms/kg CCK combinations inhibited sham feeding potently (37.6 +/- 7.0 and 62.0 +/- 9.4%, respectively). In contrast, PG and 0.25- to 0.50-microgram/kg bombesin combinations did not significantly affect sham feeding. Behavioral observations indicated that the inhibition of sham feeding by PG plus CCK did not disrupt the normal postprandial satiety sequence of behavior, PG, 400 micrograms/kg, plus 0.15 micrograms/kg of CCK did not inhibit sham drinking in 18-h water-deprived rats. PG, 400 micrograms/kg, plus 0.30 microgram/kg of CCK did inhibit sham drinking, although the effect (34.6 +/- 6.6%) was significantly less than the effect on sham feeding (75.5 +/- 9.7%) in the same rats. These data indicate that CCK is a sufficient food stimulus to permit PG to inhibit sham feeding. Furthermore, this inhibitory effect appears to result from a functional synergism of PG and CCK.

Animals↗
PubMed1987

An international survey of physician attitudes and practice in regard to revealing the diagnosis of cancer.

In 1984, questionnaires were sent to members of the International Psycho-Oncology Society concerning the practice in their country with regard to revealing the diagnosis of cancer to patients, their opinion about the effect of their policy, and their impression of local trends and attitudes toward cancer. Data from 90 respondents from 20 countries revealed that use of the word "cancer" was often avoided in discussions with the patient. Words commonly substituted for cancer were those that implied a "swelling" (e.g., tumor, growth, lump), and "inflammation," or a pathophysiologic change (blood disease, precancerous, unclean tissue). Oncologists estimated that a low percentage (less than 40%) of their colleagues revealed the word cancer in Africa, France, Hungary, Italy, Japan, Panama, Portugal, and Spain. Oncologists from Austria, Denmark Finland, The Netherlands, New Zealand, Norway, Sweden, and Switzerland, estimated the percentage to be high (greater than 80%). However, in all countries, the majority of physicians tell the family the diagnosis. The majority (90%) reported a trend toward increased telling of the diagnosis, due to greater patient information and expectations, and increased physician openess in using the word cancer. Most (68%) felt that the overall effect of revealing the diagnosis was positive. While emotional distress was transiently greater when patients were told, there were positive effects concerning coping, compliance, tolerance of treatment, planning for future, communication with physicians and others, and improved prognosis. The transient negative effects were depression, anxiety, and anger. It is important to recognize that efforts to find the "correct" position about revealing or concealing cancer diagnosis must recognize that the language between doctor and patient is constrained by cultural norms. Communication is likely to be far less dependent upon the specific words used then upon the meaning that is conveyed by the doctor.

Attitude↗