Flavor preferences conditioned by sugars: rats learn to prefer glucose over fructose.

The reinforcing effects of glucose and fructose were compared using flavor preference conditioning paradigms. Female rats given access to flavored glucose and flavored fructose solutions developed preferences for the glucose- over the fructose-paired flavor, as well as for unflavored glucose over unflavored fructose. This effect was obtained with 8% and 32% solutions, and with nondeprived and deprived rats. In most cases, the glucose preference was not immediate but appeared only after the rats had one-bottle experience with the two sugars. Female rats also preferred a glucose-paired flavor over a flavor that was paired with a noncaloric saccharin solution. A similar but somewhat weaker preference was displayed for a fructose-paired flavor over a saccharin-paired flavor. Both male and female rats acquired preferences for flavored chow that was paired with the intake of a 32% glucose solution over flavored chow paired with 32% fructose intake. Together, these results indicate that glucose has more potent postingestive reinforcing effects than does fructose. This may explain why rats consume more glucose than fructose in one-bottle acceptance as well as two-bottle preference tests.     

Prenatal flavor exposure affects growth, health and behavior of newly weaned piglets

Young animals can learn about flavors from the maternal diet that appear in the amniotic fluid and mother's milk, which may reduce neophobia for similarly flavored food types at weaning. Flavor learning may be beneficial for piglets, which after the rather abrupt weaning in pig husbandry frequently show a period of anorexia, reduced health, and stress-induced behaviors. We investigated the effects of pre- and postnatal flavor exposure through the maternal diet on acceptance of a similarly flavored food and subsequent growth, health and behavior of newly weaned piglets.Sows were offered anise-flavored (F) or control (C) food during late gestation. Piglets were cross-fostered after birth, with each sow fostering 5 piglets from an F sow and 5 from a C sow. During lactation, sows were offered F or C food, resulting in FF, CF, FC and CC piglets. Piglets were weaned on day 25 and were given both control and flavored food for two weeks using a double food choice approach.The flavored food was not preferred. Yet, prenatally exposed animals showed a higher food intake and a higher body weight in the first days after weaning, and a lower occurrence of diarrhoea than non-exposed piglets. Prenatal exposure also increased the latency to fight, and reduced oral manipulation of pen mates and mounting during the first two weeks after weaning.Prenatal exposure, but not postnatal exposure alone, to anisic flavor through the maternal diet reduced weaning-associated problems in piglets and enhanced their health and welfare in the period after weaning.     

Flavor preferences conditioned by intragastric polycose infusions: a detailed analysis using an electronic esophagus preparation

The present series of experiments examined the rat's conditioned preference for flavors associated with intragastric (IG) Polycose infusions. Adult female rats were fitted with two chronic intragastric catheters and were trained to drink flavored water (CS+; e.g., cherry-water) paired with IG infusions of 32% Polycose. On alternate days a different flavor (CS-; grape-water) was paired with IG water infusions. The flavored water and chow were available 23 hr/day. In subsequent two-choice tests the rats displayed strong preferences for the CS+ flavor (up to 98%). The CS+ preference persisted for several weeks during extinction tests when both the CS+ and CS- were paired with IG water or with no infusions. The rats also preferred the CS+ to plain water which contrasts with the mild aversion naive rats display to the flavored water. The acquired preference for the CS+ flavor was not as strong, however, as the rats' innate preferences for the taste of saccharin or Polycose. Also, unlike their response to saccharin and Polycose, the rats' acceptance (absolute intake) of the CS+ flavor was not elevated. CS+ intake was increased, though, when saccharin was added to the flavored water. The rats reversed their flavor preference when the reinforcement contingencies were reversed. Also, in the absence of unique flavor cues, the rats learned to prefer, apparently based on somatosensory cues, the sipper tube that was paired with IG Polycose infusions. The effects of flavor and IG Polycose infusions on drinking patterns and caloric intake are also described.     

Sucrose taste but not Polycose taste conditions flavor preferences in rats

Rats have an inborn preference for sweet taste and learn to prefer flavors associated with sweetness. They are also strongly attracted to the taste of glucose polymers (e.g., Polycose). This "poly" taste differs in quality from the sweet taste of sugar. To determine if poly taste, like sweet taste, conditions flavor preferences rats were trained with a distinctive flavor (CS+) added to 2% Polycose solution and a different flavor (CS-) added to plain water. In a subsequent two-bottle test the rats did not prefer the CS+ to CS- when both flavors were presented in water. In contrast, other rats significantly preferred a CS+ flavor that had been paired with 2% sucrose. Adding saccharin to a flavored Polycose solution did not improve CS+ flavor learning; rather, Polycose appeared to overshadow saccharin-induced conditioning. Flavor conditioning by a 16% Polycose solution was assessed using a sham-feeding procedure to prevent post-oral reinforcement. Although the rats sham-fed substantial amounts of the CS+ flavored Polycose solution, they failed to prefer the CS+ to the CS- flavor. This contrasts with the preference other rats displayed for a CS+ paired with sham-fed sucrose. Why attractive sweet and poly tastes differ in their ability to condition flavor preferences is not certain, although some findings suggest that they differentially activate dopamine and/or serotonin circuits involved in flavor learning.     

Conditioned enhancement of flavor evaluation reinforced by intragastric glucose. II. Taste reactivity analysis.

Rats learn to prefer a flavor that is paired with intragastric (IG) glucose infusion, which may represent a learned shift in the hedonic evaluation or palatability of the flavor. The present study used the taste reactivity (TR) test to infer nutrient-conditioned changes in flavor palatability. Rats were first conditioned in 20-h/day and then 30-min/day sessions to associate a flavored saccharin solution (the CS+) with IG infusions of 16% glucose, and a different flavored saccharin solution (the CS-) with IG water infusions. They strongly preferred the CS+ to the CS- in two-bottle intake tests. When next tested with brief intraoral (IO) infusions of the CS flavors, the rats exhibited significantly more hedonic TR responses to the CS+ flavor than the CS- flavor, which indicates an enhanced hedonic evaluation. A subsequent series of two-bottle tests established that the CS- flavor was equally preferred to 3% fructose, whereas the CS+ flavor was equally preferred to 16% fructose. In addition, the difference between the TR responses to 3% and 16% fructose paralleled the difference between the TR responses to CS- and CS+. These findings support the idea that pairing flavored saccharin with the postingestive effects of glucose produces a learned shift in palatability comparable to that produced by increasing the concentration of a sugar solution.     

Phentolamine stimulates insulin release and glucose clearance and suppresses food ingestion

In Experiment One, phentolamine (PTA), an alpha-adrenergic blocker, was injected in rats at doses of 0, 50, 100, 200, and 300 micrograms/kg following a 4-hr fast. Measurement of food intake 1-hr postinjection revealed that 300 micrograms/kg PTA reduced food intake. Experiment Two evaluated the potential aversiveness of 300 micrograms/kg PTA. Four-hour fasted rats were adapted to a milk diet as the only food source during a 1-hr intake measurement period. After the 15-day adaptation period, three separate groups of animals (n = 8 per group) received the milk with cherry flavoring added and infections of either 1% body weight 0.9 NaCl, isosmotic LiCl or 300 micrograms/kg PTA. Only those subjects that had received LiCl injections developed a reliable aversion to the cherry-flavored milk. The final experiments subdivided the 1-hr feeding period into three 20-min segments and, in separate animals, food intake or plasma insulin and glucose changes were assessed. The animals were assigned to one of two groups receiving either 300 micrograms/kg PTA or equivolume 0.9% NaCl. PTA-injected subjects showed an immediate modest enhancement of insulin release during the first 20-min feeding segment following injection, compared to controls, while blood glucose levels decreased but never differed reliably between groups. Food intake was reliably suppressed in the second and third 20-min segments for the PTA-injected rats. We advance that PTA by enhancing glucose clearance may be reducing ingestion.     

Differential reinforcing and satiating effects of intragastric fat and carbohydrate infusions in rats.

Food intake and preferences are modulated by the postingestive satiating and reinforcing actions of nutrients. This experiment compared the feeding effects of isocaloric intragastric (i.g.) carbohydrate (maltodextrin) and fat (corn oil) infusions in food-restricted rats fed low-fat (12% fat kcal) or high-fat (48% fat kcal) diets. In Experiment 1, the rats were given one flavored saccharin solution (CS+C) paired with i.g. carbohydrate infusions, a second flavor (CS+F) paired with i.g. fat infusions, and a third flavor (CS-) paired with i.g. water infusions during 30-min one-bottle training sessions. In subsequent two-bottle tests, the rats preferred both CS+s to the CS- (68-83%) and the CS+C to the CS+F (68-70%). In Experiment 2, the feeding inhibitory effects of the nutrient infusions on an ongoing meal (satiation test) or a subsequent meal (satiety test) were compared. The intake of a palatable Polycose+saccharin solution was suppressed by a concurrent carbohydrate infusion but not by a fat infusion. Also, i.g. carbohydrate preloads suppressed the intake of a subsequent (30-180 min) mixed carbohydrate+fat test meal more than did i.g. fat preloads. The satiety effects of the fat preloads were more pronounced in rats fed the low-fat diet than in rats fed the high-fat maintenance diet. Diet composition did not reliably influence the preference conditioning and satiation effects of the nutrient infusions. These results confirm prior reports that fat is less satiating than carbohydrate, and further demonstrate that i.g. carbohydrate infusions condition a stronger flavor preference than fat infusions.     

Selective effects of vagal deafferentation and celiac-superior mesenteric ganglionectomy on the reinforcing and satiating action of intestinal nutrients

The role of vagal afferents and splanchnic fibers in nutrient-induced flavor conditioning and feeding suppression was determined. Male rats were fitted with intraduodenal (ID) catheters and given subdiaphragmatic vagal deafferentation (SDA), celiac-superior mesenteric ganglionectomy (CGX), combined (COM) treatments, or sham surgery. In separate conditioning trials, they were trained to drink (30 min/day) flavored saccharin solutions paired with concurrent ID infusions of 8% maltodextrin or water and 3.55% corn oil or water. Experiment 1 revealed that SDA and sham rats showed equal preferences for the nutrient-paired flavors over the water-paired flavors. In contrast, SDA rats, unlike sham rats, failed to suppress their intake of a palatable fluid when infused intraduodenally with maltodextrin or corn oil. Experiment 2 revealed that CGX, COM and sham rats all developed preferences for the maltodextrin-paired flavor, although CGX alone or COM attenuated the conditioned preference. CGX and COM treatments also attenuated or blocked the feeding inhibitory actions of ID nutrient infusions. These findings along with prior data indicate that gut vagal afferents and splanchnic nerves are not essential for flavor-nutrient preference conditioning, whereas both vagal afferents and splanchnic nerves are implicated in carbohydrate- and fat-induced satiation.     

Experience with a flavor in mother's milk modifies the infant's acceptance of flavored cereal.

The present series of studies aimed to investigate whether experience with a flavor in mothers' milk modifies the infants' acceptance of similarly flavored foods at weaning. First, we established, using methods developed in our laboratory, that the ingestion of carrot juice by lactating women produced a sensory change in their milk approximately 2 to 3 hr after the ingestion of the beverage. Second, we randomly formed two groups of breast-fed infants who had been fed cereal for a few weeks but had only experienced cereal prepared with water. Their mothers were asked to consume one of two types of beverages (i.e., carrot juice, water) during the exposure period. Each mother was observed feeding her infant cereal during four test sessions. The first two sessions occurred during the 2 days before the exposure period; in counterbalanced order, infants were fed cereal prepared with water on 1 testing day and cereal prepared with carrot juice on the other. These two test sessions were then repeated following the exposure period. The results demonstrated that the infants who had exposure to the flavor of carrots in their mothers' milk during the exposure period consumed less of the carrot-flavored cereal and spent less time feeding when compared to the control infants whose mothers consumed the water. This may be a form of sensory-specific satiety such that the infants become less responsive to a flavor that they have been extensively exposed to in the very recent past.     

Control of feeding during saline consumption and fluid deprivation in hamsters

Cellular dehydration induced by water deprivation or hypertonic saline injection reduces feeding in a variety of species. Normal feeding in rats is maintained during isotonic saline consumption by increasing the intake of saline compared to the usual intake of water. Hamsters do not show the spontaneous preference for isotonic saline noted in rats, even after adrenalectomy. In the present investigation, feeding by hamsters was depressed during both isotonic and hypertonic saline consumption compared to the usual feeding with water. Saline intakes did not exceed water intakes under similar conditions. When fluid intakes were elevated by prior fluid deprivation, feeding rates increased at all concentrations of saline after a delay proportional to the osmolality of the solution. Positive 24-hr sodium balances were always associated with saline consumption. Water and hypertonic saline injections reduced feeding, and the fluid loads were excreted very slowly. When hamsters were fluid deprived prior to injections, saline totally suppressed feeding, while water increased feeding compared to sham injected controls. It is concluded that cellular dehydration produces a reduction of feeding in hamsters drinking isotonic or hypertonic saline. Reduced feeding with isotonic saline consumption results from the failure of hamsters to increase their ad lib intake of that solution. The prolonged retention of both sodium and fluid after saline consumption or injection suggests that further saline intake may be inhibited by an expansion of the extracellular space.     

Nutritive expectancies mediate cholecystokinin's suppression-of-intake effect

In previous studies of cholecystokinin's (CCK's) effect on consumption, physical features (e.g., taste, texture, and odor) of test meals were confounded with the nutritive expectancies elicited by those features. To separately assess the role of these two factors in supporting CCK's suppression-of-intake effect, we varied the caloric expectancies elicited by a flavored test solution, while holding constant its actual caloric density, as well as all other unconditioned stimulus features. On alternate days for a 12-day period, hungry rats drank grape or orange Kool-Aid (noncaloric) mixed with a caloric 5% ethanol solution; on the other days, they drank the alternate flavor mixed with plain water. In a subsequent choice test between the flavored solutions without ethanol, the ethanol-associated flavor (Ef) was preferred over the water-associated flavor (Wf). Two days later, the rats were injected with either cholecystokinin octapeptide (CCK-8; ip, 2 micrograms/kg) or isotonic saline, and then given access to their Ef or their Wf for 1 hr. Consumption of the Ef was suppressed by CCK-8; intake of the Wf was unaffected. These results suggest that CCK-8's effectiveness in suppressing intake of a test meal may be related not to the unconditioned stimulus features of that meal but to the nutritive expectations elicited by those features.     

Effects of hydrational state on ingestion in infant rats: is dehydration the only ingestive stimulus?

The physiological stimulus for deprivation-enhanced ingestion was studied in developing rats. During an overnight deprivation period, continuous gastric infusions of isotonic saline or milk were made to 6- and 15-day-old rat pups in order to preferentially maintain hydrational or hydrational and nutritional status, respectively. Pups' ingestion was then studied in oral-infusion tests. In 6-day-old pups that received either milk or saline infusions, ingestion was depressed relative to intake in pups that were simply deprived. But in 15-day-old pups, only milk infusions reduced intake. These findings suggest that the increased ingestion stimulated by deprivation in pups less than a week of age results primarily from dehydration, and thus that nutrient-related feeding does not emerge until later in development.     

Intracerebroventricular infusions of rat satietin into rats does not produce conditioned taste aversion

In a previous study we found that while human satietin (h-SAT) suppressed the food intake of rats it was also aversive to them. In the present study rat satietin (r-SAT) was tested for aversiveness in rats fitted with chronic third ventricle (ICV) cannulas. The rats were then given access to water for 1-hr/day and food ad lib for ten days. Fluid intake, food intake during fluid access and 24-hr total food consumption were recorded. The rats were then ICV infused with saline and 30 min later half of the animals given access to banana flavored water (Group 1) while the remainder were presented with almond flavored water (Group 2). The next day Group 1 was infused with saline and Group 2 with 100 micrograms/rat of r-SAT. Thirty minutes later the flavors presented to the rats were the reverse of the previous day. Satietin significantly reduced food intake during fluid access and for 24 hours. Thereafter, fluid and food ingestion of the groups was normal and similar. Thus no rebound feeding occurred in the r-SAT treated group. Two days after r-SAT or saline the rats were given a two-bottle choice test. Both groups displaced equal preference for the flavors, therefore r-SAT produced no taste aversion. The r-SAT treated rats lost more body weight than saline treated animals the first day after treatment. This difference increased the next day and remained significant for seven days post infusion, whereas, food consumption did not differ between the groups after the first day. The data indicate the food intake suppression in rats produced by r-SAT is not due to the compound being aversive.     

Flavor-calorie relationships: effect on weight gain in rats.

The effects of flavor variety, caloric density variety, and inconsistency of flavor-caloric density relationships on caloric intake and weight gain were studied in 36 young male rats. Lab chow was diluted with cellulose to produce three foods that differed in caloric density while having identical nutritional composition. High-density (HD) food contained 3.33 kcal/g; mid-density (MD) food contained 2.64 kcal/g; low-density (LD) food contained 2.06 kcal/g. These foods were flavored with nonnutritive powders and were used in four different feeding regimens. For 15 days, group FLAV ate MD with one of 3 flavors added daily in a 3-day rotation. Groups DENS and NOVEL rotated daily among LD, HD, and MD. One of three flavors was added to each food. For group DENS, LD always contained one flavor, MD always contained another flavor, and HD always contained the third flavor. For group NOVEL, flavor-density pairings were not consistent. A control group, CONT, ate only MD with a single flavor. Weight gain was greatest in group NOVEL. Neither density variety nor flavor variety alone enhanced weight gain relative to control. In a subsequent experiment, group NOVEL did not display a preference for a glucose-paired flavor. These results suggest that reduced orosensory control of energy balance induced by uncoupling of flavor-calorie relationships contributes to weight gain.     

Enhanced anorectic potency of naloxone in rats sham feeding 30% sucrose: reversal by repeated naloxone administration

The time-course of naloxone-anorexia was monitored in gastric-fistulated rats sham feeding sucrose (10%, 20%, 30%) solutions. Naloxone reduced sham intake dose dependently without affecting feeding initiation and in a manner which resembled the effects of progressive sucrose dilution. However, when rats sham fed 30% sucrose there was a 2-fold increase in the anorectic potency of naloxone. This exaggerated response was prevented by prior repeated naloxone treatment (5 mg/kg IP, bi-daily), concurrent with the stabilization of sham intake levels (4 days). A further experiment ruled out the possibility that tolerance develops to naloxone effects on this treatment schedule, since intact rats showed a suppression of wet mash consumption following repeated naloxone treatment which was equivalent to an acute naloxone challenge. It is proposed that 1) repeated sucrose sham feeding enhances opioid release and leads to opioid receptor adaptation (down-regulation); 2) repeated (chronic) naloxone treatments have an opposite effect on opioid receptors (up-regulation); 3) the two manipulations, in combination, counteract each other's effects. These behavioural data demonstrate dynamic changes in sham-feeding performance as a function of sucrose concentration and naloxone treatments, reinforce the importance of palatability in naloxone-anorexia, and support opioid involvement in orosensory reward.     

Intake, sweetness and liking during modified sham feeding of sucrose solutions

Although sweet solids and liquids are palatable to humans and ingested frequently when readily available, the quantitative relationship between sweet taste and intake has not been reported in humans. To investigate the quantitative relationship between sweet taste and intake directly, we adapted the modified sham feeding technique, previously used in humans for the study of the orosensory control of autonomic, neuroendocrine, and metabolic mechanisms, to measure the intake of solutions both unsweetened and sweetened with four concentrations of sucrose. By limiting the sucrose stimuli to the mouth, the modified sham feeding technique measures the orosensory stimulation of intake by sucrose in the absence of inhibitory postingestive stimulation. Nine healthy women were randomly presented with two series of five solutions of cherry Kool Aid unsweetened or sweetened with one of four concentrations of sucrose (2.5%, 5%, 10%, or 20%) in a closed opaque container fitted with a straw. They were instructed to sip as much as they wanted of the liquid during 2-min trials and to spit the fluid out into another opaque container. At the end of each trial, they used Visual Analogue Scales to rate the perceived intensities of sweetness and liking of the liquid that they had just sipped and spit. Intake, liking and perceived sweetness were significantly affected by sucrose concentration (p values相似文献   

Effects of monosodium glutamate on eating and drinking behavior in rats

The effect of monosodium glutamate (MSG) on eating and drinking behavior of rats was studied by means of preference tests in free choice situations. Low or high protein casein diets containing up to 3% MSG were selected indifferently compared to plain casein diet in 7 day trials. The acceptability of diets containing 7% MSG, particularly those of low protein level, was significantly reduced. Except for Day 1, the proportional intake (MSG flavored diet intake/total diet intake) of 9% protein--7% MSG diet was consistently lower than 18% protein--7% MSG diet. In brief exposure tests (10 min) solutions of MSG (0.02-8%) were preferred over deionized water. The acceptance of solutions containing higher concentrations of MSG was significantly reduced. The total volume intake of both choices (MSG flavored water and water) was significantly increased in tests using solutions containing 3-8% MSG. In long-term tests (1-14 days), solutions containing 0.05-1% MSG were preferred over water. The acceptance of a solution containing 5% MSG was significantly reduced. For maximum intake of moles of MSG, rats selected solutions which offered 3-5 x 10(-1) M MSG whether the experimental period was 10 min or up to 2 weeks. In a series of two choice preference tests using solutions where Na+ content and pH were kept equal, MSG was preferred over sodium acetate and over sodium glutamate but was less preferred than monosodium aspartate. The results of this study can be explained in terms of sensory quality.     

Flavor preferences conditioned by sucrose depend upon training and testing methods: two-bottle tests revisited

In confirmation of prior work, rats given one-bottle training with flavored 5% and 30% sucrose solutions (CS5 and CS30) strongly preferred the CS5 when both flavors were presented in intermediate 17.5% sucrose solutions. The CS5 preference has been attributed to a conditioned satiety response to the CS30 flavor, but equal intakes of CS5 and CS30 in one-bottle tests did not support this view. To determine if sweetness differences between training and test solutions contributed to the CS5 preference, new rats were trained and tested with flavored 10% sucrose solutions. One flavor (CS5) was paired with matched intragastric (ig) water infusions (=net 5% solution) and another flavor (CS30) was paired with matched infusions of 50% sucrose (=net 30% solution) during one-bottle training. In two-bottle tests with both flavors paired with an intermediate infusion (25%=net 17.5%), the rats initially showed no overall preference for the CS5 or CS30. Following additional training, the rats significantly preferred the CS30 to the CS5. The intragastric data suggested that a change in sweet taste context between training and testing might have accounted for the strong CS5 preference obtained in the first experiment. This was confirmed in a third experiment in which rats were trained with flavored 5% and 30% sucrose solutions and then given two-bottle tests with both flavors presented either in 5% sucrose or 30% sucrose. Rats tested with 30% sucrose strongly preferred the CS5 flavor, whereas rats tested with 5% sucrose significantly preferred the CS30 flavor. Thus, the outcome of two-bottle flavor preference tests and presumably other tests of conditioned flavor reward may be greatly influenced by the solutions used in the tests. The impact of this variable may be greatest when the training solutions do not substantially differ in their net postingestive reinforcing actions. This appears to be the case with 5% and 30% sucrose solutions because the satiating effect of the concentrated solution tends to counteract its nutrient reinforcing action.     

Conditioned aversion to amino acid flavors in the catfish, Ictalurus punctatus

Naive catfish readily accepted foof flavored with L-cysteine but generally avoided foods flavored with other amino acids. The aversions to these latter amino acids quickly disappeared after the fish had feeding experience with each. When illness induced by lithium chloride was paired with an amino acid, that flavor strongly avoided. Amino acids structurally similar to that were also avoided while other amino acid flavors were readily consumed. My studies on anosmic fish indicate that olfaction does not play a role in conditioning amino acid taste aversions. Observations of the sequential units of the feeding response suggest that sensory input to the vagal lobe of the brain is primarily responsible for taste aversion discrimination.     

Tolbutamide affects food ingestion in a manner consistent with its glycemic effects in the rat

The sulphonylurea tolbutamide possesses the ability to stimulate insulin release, produce hypoglycemia and increase food intake; however, no study has investigated the effects of moderate doses which do not produce frank hypoglycemia. Forty male rats received injections of tolbutamide at 0, 5, 15, 25 or 50 mg/kg body weight. The injections terminated a 2-hr fast and occurred at light offset, insuring a meal. Food intakes were then recorded for two hr following injection. Tolbutamide at 5 and 15 mg doses decreased food intake during the first half-hour or hour, respectively. In parallel experiments, 10 rats were sampled for blood prior to injection of tolbutamide or saline at doses cited above, and again at 10 and 40 min following injection in the absence of food. Plasma was then analyzed for insulin and glucose. Both 5 and 15 mg tolbutamide produced a mild, reliable increase in insulin accompanied by a decrease of 5 to 15 mg/dl in plasma glucose. On the other hand, the 50 mg dose produced a marked increase in insulin and a decrease of approximately 25% in plasma glucose. Thus, the present studies suggest that when endogenous insulin levels are modestly raised by tolbutamide, such that only moderate reductions of circulating glucose were observed, decreases in food intake occur.