Differential effects of glucose and fructose infusions on insulin-induced feeding in rats.

Intravenous administration of large doses of insulin rapidly lowered blood glucose concentration and elicited feeding behavior in rats. Infusion of glucose solution into the jugular vein suppressed the feeding response on a calorie-for-calorie basis. Infusion of fructose, a hexose that can nourish peripheral tissue but cannot be oxidized by brain, also lowered food intake after insulin treatment despite continued hypoglycemia. However, the effects of fructose were not as great as those of equimolar glucose solutions except when relatively small doses of insulin were given. These results provide further evidence that a peripheral factor, perhaps involving the liver, can attentuate the feeding that is initiated by acute glucoprivation.     

Effects of visceral sympathectomy on 2-deoxy-d-glucose induced eating.

The glucose anti-metabolite 2-deoxy-d-glucose (2DG) when infused through the hepatic-portal circulation caused greater food intake with shorter latency to eat than jugular vein infusion when this comparison was made in intact female rabbits. In visceral sympathectomized rabbits hepatic-portal-2DG infusions had little immediate effect on feeding whereas jugular vein infusion of 2DG had a greater effect than in intact rabbits. The results of hepatic-portal 2DG infusions support the existence of hepatic glucoreceptors and their innervation by afferents passing through the visceral sympathetic ganglia. The fact that visceral sympathetomy enhanced food intake after jugular 2DG, which probably differentially activates central glucoreceptors, suggests that CNS glucoreceptors may play an important role in feeding. However, when CNS glucoreceptors are activated by extremes of glucoprivation their effect on feeding may be masked by central sympathetic activation causing inhibition of feeding.     

Elevated blood glucose levels and satiety in the rat.

Thirteen rats were placed on a feeding schedule of two 3 hr periods of food availability daily. blood glucose levels of the experimental animals were altered by intraperitoneal injection of 8 ml of 2, 5, 8, 12, 16, 20 and 25 percent glucose solutions and by intragastric loading of 8 ml of 25, 50 and 65 percent glucose solutions in 10 different feeding experiments. In 4 additional experiments, experimental animals received intraperitoneal injections of 8 ml of 12, 16, 20 and 25 percent solutions of mannitol, a non-metabolizable sugar-alcohol. Controls always received identical quantities of mammalian Ringer's solution administered via the same route as in the experimentals. Another set of 20 rats was used to determine glucose tolerance curves for each concentration of glucose and mannitol administered. No food intake depression occurred following intraperitoneal injections of 2, 5, 8 and 12 percent glucose, 12 percent mannitol and following intragastric loading of 25, 50 and 65 percent glucose. However, intraperitoneal injections of 16, 20 and 25 percent glucose and mannitol caused depression of food intake. No depression of food intake occurred following intragastric loading of 50 and 65 percent glucose solutions which raised blood glucose levels a minimum of 43 mg percent and 55 mg percent above basal, respectively, for the duration of the 3 hr feeding period. These minimum blood glucose levels greatly exceed normal values following a meal. It was concluded that blood glucose level per se is not an important feedback parameter in the long-term control of food intake, and the depression in food intake following intraperitoneal injections of 16, 20 and 25 percent glucose and mannitol solutions was due to an abnormal physiological condition.     

Feeding inhibition and death produced by glucose ingestion in the rat

The ingestion of a 7% or 8% glucose solution by normal rats maintained on a one hr/day feeding schedule significantly suppressed food intake and body weight, and resulted in death. A 3.5% glucose solution did not have these effects, while a 21% glucose solution resulted in greater feeding and weight suppression, but no fatalities. The addition of saccharin to the glucose solutions enhanced their suppressive effects, although saccharin by itself did not reduce food intake or body weight. The results indicate that caloric depletion is not the sole cause of glucose-induced death, and some other factor(s), perhaps insulin hypersecretion, must also be responsible for this unusual effect.     

Preabsorptive intestinal satiety controls of food intake in pigs.

Pigs, 1--3 mo of age, weighing 5--80 kg, were fitted with duodenal, intraportal, or intrajugular catheters. After a 4-h fast, preloads were delivered to the duodenum, and food intake then measured for 10 min (no drinking water). Glucose (5--40%) and NaCl (0.9--6.5%) solutions were used as preloads (5 ml/kg body wt). Food intake expressed as percent control intake (Y) was depressed in proportion to preload concentration (X): for glucose, Y = 109 - 2X; for NaCl, Y = 107 - 13X. When expressed in osmoconcentration, glucose and NaCl preloads had nearly identical satiety effects. Preloads of 40% sorbitol depressed intake to 74% control. Intrathoracic vagotomy reduced the satiety effects of glucose and NaCl solutions by 50%. Tetracaine (0.5%) in the hypertonic preloads blocked 80% of the satiety effects of the glucose and NaCl preloads, but had no effect on sorbitol satiety effect. Injection of glucose or NaCl solutions into the portal or jugular veins had no significant effect. It was concluded that duodenal osmoconcentration to the degree that it exceeds body fluid tonicity contributes to the immediate satiety seen during a meal.     

Deficits in glucose appetite and satiety produced by ventromedial hypothalamic lesions in the rat

Rats with ventromedial hypothalamic lesions displayed a reduced sensitivity to dilute (5 or 7%) glucose solutions. The lesioned animals were less responsive to the food suppressive effects of glucose ingestion, and they drank less dilute glucose when food deprived compared to controls. The VMH lesioned rats, on the other hand, appeared normally sensitive to concentrated (20 or 33%) glucose solutions. They suppressed their feeding in response to glucose intubation, and they consumed more concentrated glucose solution than did controls, which is consistent with the hyperphagia effects of the lesions. The nature of the neural impairment responsible for these lesion effects is discussed.     

Caloric imbalance induced by failure of food intake to compensate for caloric supply provided by diurnal or nocturnal drinking of isotonic glucose

Free-feeding rabbits allowed to drink isotonic glucose failed to reduce food intake sufficiently to compensate for the extra caloric supply. This resulted in a considerable caloric imbalance which was not compensated during the diurnal or nocturnal periods when the animals were drinking glucose. Reductions of food intake were smaller or even paradoxically reversed following repeated exposures to glucose despite the fact that the intake of fluids was more doubled. Equi-osmotic equi-volumic saccharin solutions drank voluntarily or infused into the duodenum did not produce paradoxical feeding response. Blockade of insulin-dependent lipogenesis by Atromid S prevented the paradoxical stimulation of food intake by larger duodenal loads of glucose.     

Inhibition of food intake in the rat following complete absorption of glucose delivered into the stomach, intestine or liver.

1. Solutions of glucose or other carbohydrates were administered during the dark or light period of the circadian cycle to rats which had been only briefly deprived of food. 2. food was restored to the animals at various times after administration of a glucose load by stomach tube. With delays between loading and access to food of up to 3 hr by night and 2 hr by day, subsequent food intake was less than intake after non-nutritive loads. 3. measurement of the glucose content of the gastrointestinal tract at various times after glucose loading showed that this depression of intake was still apparent even when the rat was offered food some time after complete absorption of the stomach load. 4. infusion of a glucose solution into the duodenum or the hepatic protal vein also inhibited subsequent food intake. 5. in all cases, the inhibition of food intake was expressed as a decrease in the size of the first meal after restoring access to food. 6. these results provide the first demonstration that the entry of normal amounts of carbohydrate into the body by the physiological route is followed by depression of food intake which lasts until after absorption is complete.     

Reflex insulin secretion due to central hyperglycemia promoted by intracarotid glucose infusion in dogs

The reflex insulin secretion was investigated by glucose infusions (10 ml of 3% solutions) into the carotid artery or the jugular vein in anesthetized and unanesthetized, untrained dogs. Neither intrajugular nor intracarotideal glucose infusions changed the peripheral glycemic level in any of the experiments. Reflex insulin secretion did occur when glucose was injected into the carotid artery under pentobarbital anesthesia (30 mg/kg IV), but not in unanesthetized animals. Saline infusion into the carotid artery or glucose into the jugular vein in both groups did not elicit a significant increase in insulin secretion.     

Behavioral compensatory responses to continuous duodenal and upper ileal glucose infusion in rats

A 30% glucose solution contributing 38% of the rats' normal voluntary daily energy intake was infused continuously for 24 hr into the intestines of two groups of rats, one catheterized in the duodenum and one in the upper ileum. Both groups responded by a compensatory reduction in voluntary food intake which was achieved by a statistically significant reduction in meal size but not in meal number. No significant change in food intake behavior occurred during similar infusion of equiosmotic NaCl solution, physiological saline or water. No significant differences in food intake behavior were observed between the group infused duodenally and the one infused intraileally. These findings suggest that, first, if an intestinal satiety mechanism exists, it is not exclusively located in the duodenum and, second, that any specific duodenal factors such as cholecystokinin are not indispensable in the control of meal-taking behavior.     

Food intake of rats administered with glycerol

The effect of glycerol on rats food intake was determined when it was administered either via bolus gastric intubation, or by a continuous 24 hr infusion into the aorta. Both of these treatments resulted in a suppression of the 24 hr food consumption to an extent which was greater than that accounted for by the caloric value of the administered metabolite. Gastric loading with urea solutions equiosmotic to glycerol or with glucose solutions equicaloric to glycerol were less effective than glycerol in reducing the 24 hr food intake. The time course effect on food intake varied between gastric loading with glycerol and with equicaloric glucose solutions, with the former usually exerting a more delayed and longer lasting effect. Continuous intraaortal infusions of glycerol were more effective than glucose solutions in suppressing 24 hr food intake even though the latter had twice the caloric value of the former. Our data suggest that the action of glycerol on food intake is not mediated through its conversion to glucose. The possibility that glycerol may participate in a lipostatic control mechanism of food intake is discussed.     

Effects of glucose and saccharine solutions on subsequent food consumption

Twenty three hr water deprived animals were given access to various glucose and glucose + saccharin solutions during a 1 hr drinking session. Subsequent 1 hr and 22 hr food intakes were measured. Results indicate that more food was consumed during the first post drinking hour by the animals when receiving 3.5% GLU + 0.25% SACC while comparatively less food was consumed by them following the ingestion of 21% GLU and 21% GLU + 0.25% SACC. During the remaining 22 hr when the animals received 21% GLU and 21% GLU + 0.25% SACC they increased their food intake such that total 23 hr food intake was unaffected. Food intake was not related to the amounts of the different fluids consumed but appeared to be determined by other oral and post ingestion factors associated with the different solutions.     

The lack of effect of intrajugular or intraportal injections of glucose or amino-acids on food intake in pigs

Pigs have been trained to press a panel switch with their snouts in order to obtain food as reinforcement on a Fixed Ratio 5 schedule. The pigs were allowed to feed to satiety only once each day in the operant situation. The pigs were provided with catheters in their jugular or portal veins and while they responded on the panel to obtain food, intrajugular or intraportal injections of 500 ml of 15% glucose solution or 500 ml of 0.9% saline were injected. Neither of these procedures significantly reduced the rate of responding or the total amount of food eaten when compared with trials in which no injections were given. It was also shown that the intraportal injection of 250 ml of a 10% solution of amino acids did not reduce the food intake of the pigs or influence the response rate.     

Some determinants of intake of glucose+saccharin solutions

In the present three experiments, tests were run to see if postingestional factors played a role in the excessive drinking elicited by the combination of 3% glucose and 0.125% saccharin solutions. The first experiment showed a marked increase in the total daily caloric intake and a decrease in the proportion of calories taken from the food when the glucose+saccharin (G+S) solution was presented to rats. In spite of this alteration of diet induced by G+S drinking, Experiment 2, which compared the drinking of various concentrations of glucose solutions and G+S solutions, demonstrated that the rat drinks these large quantities of the G+S solution for taste, not calories. The final experiment compared preference tests on various concentrations of saccharin, glucose or G+S solutions and showed that preference data across concentrations of G+S were qualitatively similar to the saccharin preference data, and different from the glucose data, even though it was the amount of glucose in the concentrations that was manipulated.     

Effect of insulin on sex differences in the intake of glucose solutions in rats

Adult male and female Wistar rats maintained on ad lib diet were given a choice between tap water and a solution of glucose in the concentration of either 5 or 12%. Both sexes exhibited a marked preference for glucose solutions. With the 5% solution the volume intake was similar in both sexes and the total calorie intake was normal. With the 12% solution the volume intake was higher in females than in males, while in both sexes the total calorie intake was increased to a similar (maximum acceptable) level. Treatment with Protamine Zinc Insulin (PZI) in a daily dose of 40 U/kg b.w. markedly increased the intake of the 5% solution in both sexes, but significantly more in females than in males, thus revealing sex differences which were not manifest in untreated rats. PZI treatment had little effect on 12% glucose solution intake, presumably because with this solution the total calorie intake was increased to a maximum already in untreated rats.     

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.     

Failure of portal glucose and adrenaline infusions or liver denervation to affect food intake in dogs

Total liver denervations were attempted on 5 mongrel dogs. At the same time, the hepatic portal vein was cannulated with a polyethylene cannula which was exteriorized. Five sham operated, cannulated dogs served as controls. Both denervated and sham operated dogs returned to preoperative food intake within 8 days post surgery. After recovery, intraportal infusions of 6 to 25 g of glucose prior to food presentation in 23 hr fasted sham or denervated dogs resulted in no anorexia. The portal vein and jugular vein were cannulated in an additional 4 dogs. Jugular blood samples were taken prior to and after portal infusion of 20 g of glucose in 23 hr fasted dogs. Both jugular blood glucose and insulin concentration increased significantly 1 to 2 min after portal infusion. The dogs were presented with food 3 to 5 min after the cessation of infusion, yet they showed no anorexia. These same 4 dogs were given portal infusions of either 0.5 μg/kg, 1.0 μg/kg or 1.5 μg/kg of adrenaline after a 23 hr fast. When food was presented 10 min after the infusions were stopped, the dogs ate immediately showing no signs of anorexia. These results question the role or the existence of hepatic glucoreceptors in the control of food intake in the dog.     

Post-oral infusion sites that support glucose-conditioned flavor preferences in rats

Rats learn to prefer a flavored solution (CS+) paired with a gastrointestinal glucose infusion over an alternate flavor (CS−) paired with a non-caloric infusion. Prior work implicates a post-gastric site of glucose action, which is the focus of this study. In Exp. 1, male rats (8-10/group) were infused in the duodenum (ID), mid-jejunum (IJ), or distal ileum (II) with 8% glucose or water as they drank saccharin-sweetened CS+ and CS− solutions, respectively, in one-bottle 30-min sessions. Two-bottle tests (no infusions) were followed by a second train-test cycle. By the second test, the ID and IJ groups preferred the CS+ (69%, 67%) to the CS− but the II group did not (48%). Satiation tests showed that ID and IJ infusions of glucose reduced intake of a palatable solution similarly, while II infusions were ineffective. In Exp. 2, rats (10/group) drank CS solutions in one-bottle, 30-min sessions and were given 2-h ID or hepatic portal vein (HP) infusions. The CS+ and CS− were paired with 10 ml infusions of 10% glucose and 0.9% saline, respectively. Following 8 training sessions, the ID group preferred the CS+ (67%) to the CS− but the HP group did not (47%) in a two-bottle test. The similar CS+ preferences displayed by ID and IJ, but not II groups implicate the jejunum as a critical site for glucose-conditioned preferences. A pre-absorptive glucose action is indicated by the CS+ preference displayed by ID but not HP rats in Exp. 2. Our data were obtained with non-nutritive CS solutions. HP glucose infusions are reported to condition preferences for a flavored food that itself has pre- and post-absorptive actions. Thus, there may be multiple sites for glucose conditioning with the upper or mid-intestines being the first site of action.     

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)     

The effects of caerulein on food intake in the cat

The effects of physiological doses of caerulein, a pure cholecystokinin analog, was measured on food intake of cats. Food intake was increased by caerulein when infused at 400 ng/kg/hr. However, at the lowest dose, a slight decrease of intake was observed suggesting that low levels of caerulein may inhibit food intake in this species. Slow infusion of caerulein as compared to bolus injection may have opposite effects on food intake, that is, stimulation with infusion and inhibition with injection.