PubMed Health⌕ Search

Biomedical subjects

S C Woods

Publications and source records attributed to S C Woods.

At least 19 recordsLinked to original sources
PubMed1992

Intraventricular neuropeptide Y injections stimulate food intake in lean, but not obese Zucker rats.

We examined the effect of acute third intraventricular (IVT) injections of either saline or NPY (0.95, 3.0, 9.5, or 30.0 micrograms in 1 microliter) on the 1-, 4-, and 22-hour postinjection food and water intake of female obese (fa/fa), heterozygous lean (Fa/fa), and homozygous lean (Fa/Fa) Zucker rats. None of the doses of NPY had an effect on either food or water intake of fa/fa rats. A significant increase of food intake was seen in Fa/Fa rats at 1 and 4 hours after the 3.0 micrograms injection of NPY and at 1, 4, and 22 hours after the 9.5 micrograms injection of NPY. Both 3.0 and 9.5 micrograms of NPY also stimulated 1- and 4-hour postinjection food intake of Fa/fa rats, although this effect was significant only at 4 hours after the 3.0 micrograms dose. NPY had a less reliable effect on water intake; 3.0 micrograms of NPY stimulated 1-hour postinjection water intake of Fa/fa rats and 4-hour postinjection water intake of Fa/Fa rats. These results indicate that lean, but not obese Zucker rats, respond by eating more to centrally administered NPY. This deficit is similar to the effects seen with IVT insulin injections and may be a result of a common receptor-mediated mechanism.

Animals↗
PubMed1992

Neuropeptide Y paradoxically increases food intake yet causes conditioned flavor aversions.

Neuropeptides have been implicated in the short-term regulation of food intake and the long-term control of body weight. Previous studies have shown that central administration of neuropeptide Y (NPY), the most abundant of these peptides in the brain, produces robust increases of food intake. We now report that NPY, at doses that stimulate food intake when administered intraventricularly, also causes the formation of robust conditioned flavor aversions when given via the same cannula and at the same dose. This apparently paradoxical effect may be indicative of different populations of central NPY receptors having dissimilar effects on ingestive behaviors. The results also suggest that the use of conditioned aversions to investigate drug-induced malaise may not be appropriate when applied to ingestive behaviors.

Animals↗
PubMed1992

Intraventricular CCK-8 reduces single meal size in the baboon by interaction with type-A CCK receptors.

Intraventricular cholecystokinin COOH-terminal octapeptide (CCK-8) decreases meal size in the meal-trained baboon. In the present study, we tested whether this action is mediated by CCK-A receptors, CCK-B receptors, or both. Intraventricular administration of the selective CCK-A receptor agonist A71623 at 1 and 10 nmol/kg suppressed 30-min meal size 69 +/- 22% and 75 +/- 7%, respectively. Additionally, intraventricular A71623 was equipotent to CCK-8 at 1 nmol/kg (% suppression of meal by CCK = 59 +/- 17). However, intraventricular administration of the CCK-B receptor agonist A63387 at 10 nmol/kg had no effect on 30-min meal size (% suppression = 18 +/- 29). Intravenous administration of 10 nmol/kg A71623 did not result in an alteration of meal size, but prandial plasma insulin and glucose responses were delayed and blunted. Basal plasma insulin levels doubled after intravenous administration of A71623. Both behavioral and metabolic responses to A71623 in the baboon are virtually identical to those we have previously observed after CCK-8 treatment. Thus we conclude that the predominant receptor population with which intraventricular CCK-8 interacts are type-A CCK receptors that are accessible to the ventricular system of the baboon.

Animals↗
PubMed1992

Intraventricular corticosterone increases the rate of body weight gain in underweight adrenalectomized rats.

Circulating glucocorticoids are necessary for hyperphagia and excessive weight gain in obese rodents. It has been reported that intraventricular administration of selected glucocorticoids restores hyperphagia and weight gain in anorexic adrenalectomized gold thioglucose-treated mice. We wanted to determine whether administration of glucocorticoids directly into the central nervous system of normal (nonobese) rats will enhance the rate of weight gain. In the initial experiment rats were allowed ad libitum access to chow or were rendered underweight by a 7- to 10-day period of food restriction. Animals were then adrenalectomized or sham operated and allowed ad libitum access to chow. Both groups of adrenalectomized animals consumed less food and gained weight less rapidly than their respective sham controls. Previously food-restricted and therefore underweight adrenalectomized rats consumed significantly more food and gained weight more rapidly than previously ad libitum-fed adrenalectomized rats. These data support the conclusion that adrenalectomized rats, like intact rats, regulate their weight, albeit at a lower level than intact rats. To determine a possible role of central glucocorticoids in this phenomenon, food-restricted or ad libitum-fed rats received a single intraventricular injection of corticosterone or its vehicle on the day after adrenalectomy or sham surgery. Whereas intraventricular corticosterone had no effect on weight gain in ad libitum-fed rats, it significantly increased the rate of weight gain in food-restricted adrenalectomized rats relative to that in vehicle-treated controls. Peripheral administration of corticosterone had no effect in this paradigm. It is concluded that glucocorticoids act directly on the central nervous system of underweight lean rats to augment weight gain.

Adrenalectomy↗
PubMed1992

Inhibition of hypothalamic neuropeptide Y gene expression by insulin.

Insulin acts in the brain to suppress feeding, whereas neuropeptide Y (NPY) has the opposite effect. Since fasting lowers plasma insulin levels and increases hypothalamic synthesis of NPY, we proposed that insulin may inhibit hypothalamic NPY gene expression. To test this hypothesis, we used RIA and in situ hybridization histochemistry to determine if centrally administered insulin could reduce levels of both NPY and its messenger RNA (mRNA) in discreet hypothalamic regions during fasting. Three groups of Long-Evans rats were entered into a 72-h study protocol. One group was fed ad libitum during this period, while the others were fasted. Fed rats received intracerebroventricular (icv) injections of saline vehicle at 12-h intervals, whereas fasted groups received icv vehicle alone or with insulin (4 mU/12 h). In vehicle-only treated rats, fasting significantly increased expression of preproNPY mRNA in the arcuate nucleus to 179 +/- 20% of fed controls. Administration of icv insulin during fasting abolished this increase (99 +/- 14% of fed controls; P less than 0.05 vs. fasted, vehicle-treated rats). Central insulin administration during fasting also reduced immunoreactive NPY concentrations in samples punched from the paraventricular nucleus (PVN) (875 +/- 122 pg/punch) to levels below vehicle-only treated rats (1396 +/- 435 pg/punch; P less than 0.05), similar to free-feeding control values (814 +/- 170 pg/punch). By comparison, neither fasting nor central insulin administration altered NPY levels in four other hypothalamic regions (supraoptic, ventromedial, dorsomedial, and arcuate nuclei). Continuous icv insulin infusion at a lower dose (2 mU/day) produced a similar result during a shorter period (48 h) of food deprivation in Wistar rats. In this study, central insulin infusion also inhibited the fasting-related increase in arcuate preproNPY mRNA levels and did not affect plasma glucose or insulin levels. This suggests that insulin acts locally to inhibit hypothalamic NPY mRNA expression. We conclude that the increase of levels of NPY in the PVN and preproNPY mRNA in the arcuate nucleus during fasting are inhibited by icv insulin. Fasting, therefore, increases NPY biosynthesis along an arcuate nucleus-PVN pathway in the hypothalamus via a mechanism dependent on low insulin levels.

Animals↗
PubMed1991

Intraventricular insulin reduces food intake and body weight of marmots during the summer feeding period.

The study presented below describes experiments that investigate the ability of insulin to inhibit food intake in awake, active marmots during the summer season. Our results suggest that increasing intraventricular insulin concentration during the summer active feeding period will cause a decrease in food intake and body weight of marmots. When infused with insulin into their lateral ventricles (Alzet #2002 minipumps), animals had significantly lower food intake as compared to their food intake during the control period. In addition, these animals lost body weight during the period of the insulin infusion. We suggest that during the summer when marmots are not hibernating and are actively feeding, brain insulin levels may play a role in regulating food intake.

Adipose Tissue↗
PubMed1991

The eating paradox: how we tolerate food.

It is hypothesized that food, which is certainly a necessary commodity with powerful positive reinforcing qualities, also provides a potential threat to organisms, including humans. The act of eating, although necessary for the provision of energy, is a particularly disruptive event in a homeostatic sense. Just as humans learn responses to help them tolerate the administration of dangerous drugs, so do they learn to make anticipatory responses that help minimize the impact of meals on the body, to limit the amount of food consumed within any individual meal, to recruit several parts of the protective stress-response system while meals are being processed, and to limit postprandial behaviors so as to minimize the possibility of disrupting homeostatic systems even more. It is further hypothesized that defenses against eating too much may become activated inappropriately and contribute to clinical problems such as reactive hypoglycemia.

Animals↗
PubMed1991

Seasonal changes in CSF insulin levels in marmots: insulin may not be a satiety signal for fasting in winter.

Plasma insulin (PI) reportedly crosses the blood-brain barrier in mammals and acts with the central nervous system (CNS) to reduce food intake. Animals that hibernate (hibernators) eat little or no food from early winter (November) to spring (April). This lack of food intake may be due to elevated PI concentrations acting within the CNS. In this study, we determined whether hibernators have altered insulin levels within the CNS at different times during the circannual cycle of metabolism and feeding. Plasma and cerebrospinal fluid (CSF) immunoreactive insulin concentrations were measured in marmots (Marmota flaviventris) during the feeding phase of the body weight cycle and during the fasting period (hibernation). Basal plasma and CSF samples were collected in September, November, January, and April. In addition, plasma and CSF insulin levels were monitored during a 2-h intravenous infusion of glucose (20% wt/vol) that stimulated pancreatic B-cell production of insulin. During the spring feeding period, we found that as PI levels rise, so do CSF insulin concentrations. However, in fall and winter when marmots are fasting, very little insulin entered the CSF even when PI levels were significantly elevated. Furthermore, the longer the fast, the lower was the CSF insulin under both basal and infusion conditions. These results lead us to conclude that elevated CSF insulin is not a likely cause of suppressed food intake in fasting marmots.

Animals↗
PubMed1991

Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport.

To study the route by which plasma insulin enters cerebrospinal fluid (CSF), the kinetics of uptake from plasma into cisternal CSF of both insulin and [14C]inulin were analyzed during intravenous infusion in anesthetized dogs. Four different mathematical models were used: three based on a two-compartment system (transport directly across the blood-CSF barrier by nonsaturable, saturable, or a combination of both mechanisms) and a fourth based on three compartments (uptake via an intermediate compartment). The kinetics of CSF uptake of [14C]inulin infused according to an "impulse" protocol were accurately accounted for only by the nonsaturable two-compartment model (determination coefficient [R2] = 0.879 +/- 0.044; mean +/- SEM; n = 5), consistent with uptake via diffusion across the blood-CSF barrier. When the same infusion protocol and model were used to analyze the kinetics of insulin uptake, the data fit (R2 = 0.671 +/- 0.037; n = 10) was significantly worse than that obtained with [14C]inulin (P = 0.02). Addition of a saturable component of uptake to the two-compartment model improved this fit, but was clearly inadequate for a subset of insulin infusion studies. In contrast, the three-compartment model accurately accounted for CSF insulin uptake in each study, regardless of infusion protocol (impulse infusion R2 = 0.947 +/- 0.026; n = 10; P less than 0.0001 vs. each two-compartment model; sustained infusion R2 = 0.981 +/- 0.003; n = 5). Thus, a model in which insulin passes through an intermediate compartment en route from plasma to CSF, as a part of a specialized transport system for the delivery of insulin to the brain, best accounts for the dynamics of this uptake process. This intermediate compartment could reside within the blood-CSF barrier or it may represent brain interstitial fluid, if CNS insulin uptake occurs preferentially across the blood-brain barrier.

Animals↗
PubMed1991

Central insulin administration reduces neuropeptide Y mRNA expression in the arcuate nucleus of food-deprived lean (Fa/Fa) but not obese (fa/fa) Zucker rats.

By acting in the brain, insulin suppresses food intake, whereas neuropeptide Y (NPY) has the opposite effect. Since fasting increases NPY gene expression in the hypothalamic arcuate nucleus (ARC) and also lowers circulating insulin levels, we hypothesized that the anorexiant effect of insulin could result from insulin inhibition of NPY gene transcription in the ARC. Therefore, we determined whether the administration of insulin (200 mU per 12 hrs) into the 3rd cerebral ventricle of lean (Fa/Fa) female Zucker rats (n = 5) during 48 hrs of food deprivation reduces the expression of preproNPY mRNA in the ARC compared to vehicle-treated controls (n = 5). Coronal sections of rat brain were hybridized with an oligonucleotide probe complementary to preproNPY mRNA and apposed to x-ray film. Hybridization was quantified in both the ARC and the hippocampal dentate gyrus by computerized image analysis of the resulting autoradiographs. Central insulin significantly reduced the area of hybridization in the ARC (0.235 +/- 0.017 mm2; mean +/- SE) compared to vehicle-treated controls (0.331 +/- 0.037 mm2; p less than 0.05), but was without effect in the hippocampus. Thus, insulin reduced the expression of mRNA for NPY specifically in the ARC. Since the genetically obese (fa/fa) Zucker rat is insensitive to the anorexiant effect of insulin and over-expresses NPY in the ARC, we next tested the hypothesis that insulin does not suppress NPY mRNA expression in the ARC of these rats. Consistent with this hypothesis, central insulin administration to obese Zucker rats during 48 hrs of food deprivation (n = 6) did not lower hybridization area in the ARC compared to vehicle alone (n = 4) (0.286 +/- 0.036 vs. 0.248 +/- 0.019 mm2; p greater than 0.05). We conclude that insulin suppresses the expression of mRNA for NPY in the ARC of fasted lean but not obese Zucker rats. Regulation of hypothalamic NPY gene expression by insulin may account for its anorexiant effect, and a defect in this action may contribute to certain forms of obesity.

Animals↗
PubMed1990

Kinetics and specificity of insulin uptake from plasma into cerebrospinal fluid.

To characterize the relationship between insulin levels in plasma and those in cerebrospinal fluid (CSF), we studied the kinetics of both the uptake of insulin into CSF from plasma and the turnover of insulin within the CSF compartment. Sustained physiological levels of euglycemic hyperinsulinemia (plasma insulin approximately 500 pM) did not alter CSF insulin levels within the 1st h, but by 90 min a significant increase was observed (P less than 0.01). During graded hyperinsulinemic clamps (mean plasma insulin approximately 500-15,000 pM), CSF insulin rose in a dose-dependent fashion. This rise was characterized by an initial delay followed by a continuous increase for the next 150 min. We also found that after brief, high-dose intravenous insulin infusions, the t1/2 of CSF insulin was 143 +/- 7 min (means +/- SE; n = 4), similar to that of CSF turnover by bulk flow. To test the specificity of CSF insulin uptake from plasma, we compared this uptake during intravenous insulin infusions with that of proinsulin, a peptide with reduced affinity for the insulin receptor. We observed a significantly lower increment of CSF proinsulin levels over 180 min (13.6 +/- 1.6 pM; means +/- SE; n = 4) compared with that of insulin (22.4 +/- 0.6 pM; n = 4; P less than 0.01), despite plasma proinsulin levels higher than insulin (1,890 +/- 287 vs. 1,283 +/- 192 pM; P less than 0.001). When corrected for the difference in plasma levels, the uptake of insulin was fivefold greater than that of proinsulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Evidence for separate receptors for insulin and insulin-like growth factor-I in choroid plexus of rat brain by quantitative autoradiography.

Binding of insulin and insulin-like growth factor-I (IGF-I) to the choroid plexus was quantitatively characterized using autoradiography and computer densitometry. Slide-mounted brain slices were incubated in 0.1 nM [125I]-insulin or [125I]-[Thr59]IGF-I. To determine specificity of the binding sites, the labeled peptides were mixed with unlabeled analogues. Autoradiography was done with LKB Ultrofilm and analyzed with a computer image analysis system and program for densitometry. Results showed that binding was time and temperature dependent and reversible. Binding of the iodinated insulin and IGF-I was inhibited by unlabeled peptides in a dose-dependent manner. The rank order of potency of these peptides in competing for the choroid plexus iodoinsulin binding sites was: chicken insulin greater than porcine insulin greater than desoctapeptide insulin greater than IGF-I. IGF-I was more potent than porcine insulin in competing for the choroid plexus iodolGF-I binding sites. Somatostatin was ineffective. Non-linear regression analysis revealed the presence of high- (Kd 1.3 +/- 0.2 nM) and low-affinity (Kd 36 +/- 1.4 nM) binding sites for insulin and a single high-affinity binding site (Kd 3.1 +/- 0.3 nM) for IGF-I in the choroid plexus. There were approximately 50 times more binding sites (Bmax) for IGF-I than for insulin high-affinity sites, whereas the number of low-affinity sites for insulin was about equal to the number of IGF-I high-affinity sites. The results of these binding studies with iodinated insulin and [Thr59]IGF-I support the conclusion that the rat choroid plexus has separate high-affinity receptors for insulin and IGF-I, and that the IGF-I receptors outnumber the insulin receptors.

Animals↗
PubMed1990

A re-assessment of the regulation of adiposity and appetite by the brain insulin system.

We have provided strong support for the hypothesis that the pancreatic hormone, insulin, provides a signal to the brain indicating the level of adiposity. Because insulin is found in the cerebrospinal fluid (CSF) in direct proportion to plasma levels, and because changes of plasma insulin result in subsequent changes of CSF insulin, we previously hypothesized that the blood-borne insulin signal enters the central nervous system by initially entering the CSF and then diffuses into the brain. Such a route explained the time lag for influences of insulin upon food intake and body weight. Recent evidence suggests that insulin may enter the brain directly through brain capillaries, raising the possibility that what is measured in the CSF may not be indicative of insulin on its way into critical brain areas. Implications of this change of route of entry of insulin into the brain for the regulation of food intake and body weight are discussed.

Adipose Tissue↗
PubMed1989

IVT CCK-8 is more effective than IV CCK-8 at decreasing meal size in the baboon.

In this study, we compared the effectiveness of intravenous (IV) vs. intraventricular (IVT) cholecystokinin octapeptide (CCK-8) to decrease single meal size over a dose range of 0.1 to 4.0 micrograms/kg in a population of overnight fasted baboons. IV CCK did not decrease meal size significantly at doses of 0.5, 1, and 4 micrograms/kg (84 +/- 22%, 78 +/- 12%, and 89 +/- 33% of paired control meal sizes respectively). IVT CCK significantly decreased single meal size at all doses tested (40 +/- 18%, 26 +/- 10%, 37 +/- 15%, 26 +/- 12%, and 12 +/- 6% of paired control meal sizes at 0.1, 0.25, 0.5, 1, and 2 micrograms/kg respectively). Meal suppression with IVT CCK was significantly greater than that achieved with IV CCK at doses of 1 and 2 micrograms/kg. We conclude that in the baboon, CCK may have a direct effect at the central nervous system to suppress single meal size.

Animals↗
PubMed1989

The regulation of food intake by peptides.

Historically, nutrients and related metabolic signals were considered to control the onset and offset of meals. Recent research has focused upon the roles of peptides found in the gastrointestinal tract and brain as alternate controllers of these processes. During a meal, the gut secretes a variety of peptides as part of the digestive process. Some of these substances, acting as hormonal or as local signals, may also provide information which is relayed to the central nervous system, causing eating to stop and producing the sense of satiety. When administered to animals or people before a meal, exogenous cholecystokinin (CCK), the most studied of the putative satiety peptides, reduces food intake in a dose-dependent manner. Recent findings support the concept that endogenous CCK acts during meals to limit meal size, and evidence is reviewed suggesting a possible pathophysiological role for CCK in bulimia. Adiposity is also regulated via peptide hormones, especially insulin. Insulin is secreted in direct proportion to adiposity, and blood-borne insulin gains access to brain areas important in the regulation of feeding. The administration of insulin into the brain causes reduced eating and weight loss.

Adipose Tissue↗
PubMed1989

Intraventricular CCK inhibits food intake and gastric emptying in baboons.

To evaluate the role of cholecystokinin (CCK) as a physiological regulator of meal size and gastric emptying in the baboon, we measured plasma CCK bioactivity during 30-min meals alone and after intravenous or intraventricular infusions of CCK COOH-terminal octapeptide (CCK-8). Both intravenous (2 micrograms/kg) and intraventricular (1 microgram/kg) CCK-8 administration resulted in plasma CCK elevations comparable with normal prandial CCK levels: peak plasma levels were 4.1 +/- 0.9, 7.1 +/- 1.1, and 4.9 +/- 2.2 pM for pooled intravenous and intraventricular control, intravenous, and intraventricular conditions. Also, both treatments appeared to reduce gastric emptying as indicated by a significant suppression of postprandial plasma insulin and glucose levels. However, only intraventricular CCK reliably reduced meal size (percent of control meal size was 91 +/- 5% or 43 +/- 19% with intravenous or intraventricular CCK). We conclude that circulating endogenous CCK is a potent postprandial endocrine regulator of gastric emptying. However, the ability of CCK to decrease meal size may require direct interaction with the central nervous system.

Animals↗
PubMed1988

Insulin responses and glucose levels in plasma and cerebrospinal fluid during fasting and refeeding in the rat.

The present experiments were designed to investigate the rate of penetration of insulin from the plasma into the cerebrospinal fluid (CSF) during 24 hr of fasting and refeeding in the light phase. The results show that under these conditions basal CSF-immunoreactive insulin (IRI) levels were positively correlated with plasma IRI levels. Basal plasma IRI fell during a fast but was similar to prefast control after one day of refeeding. Although CSF-IRI levels rose during glucose infusion, CSF-IRI was not elevated by glucose during a fast. During refeeding, CSF-IRI responses returned toward control, prefeeding values. This study suggests a decreased transport of insulin from plasma to CSF during fasting. The lower CSF-IRI levels achieved under these conditions may determine meal size by allowing larger meals after a fast.

Animals↗