Mauricio Russek

Demonstration of the influence of an hepatic glucosensitive mechanism on food-intake.

Abstract The intraportal injection of 3–12 g of glucose through a chronic cannula produced a 40–75 min anorexia in 22 hr fasted dogs that would normally eat 500 g of dry food without interruption. The same amount of glucose injected into a jugular cannula did not elicit any anorexia. The intraportal injection of an equal volume of isosmotic NaCl did not produce any noticeable change in the feeding behavior of the same dogs. Therefore, the satiating effect was obtained only when the glucose went directly into the liver and not when distributed throughout the organism.

Hepatic receptors and the neurophysiological mechanisms controlling feeding behavior.

Publisher Summary There are at least seven theories or hypotheses about food intake control, none of which explains the matter satisfactorily. This has led most of the workers in this field to consider the control of feeding as multifactorial. In the exposition of various theories and hypotheses in this chapter, no exhaustive survey of literature is attempted. On the contrary, only some of the main data supporting and contradicting them have been selected. In the elaboration of the new hypothesis proposed in the chapter, a combination of published and unpublished facts and direct deductions and speculations from these data is made, hoping to stimulate experimental work that will substantiate or disprove the ideas presented. The chapter discusses the subject of food intake control by presenting the experimental facts about the areas of the CNS related to the integration of feeding behavior, because most workers in the field are in general agreement concerning this subject.

Hypothetical liver receptors and the anorexia caused by adrenaline and glucose

Abstract I.p. Adrenaline (0.1 mg/kg) in dogs elicited a prolonged anorexia (45 min to more than 2 hr) accompanied by mild hyperglycemia. The anorexia, but not the hyperglycemia, was easily conditioned either to the experimental situation or to a visual stimulus. I.v. glucose (300 mg/kg) produced similar hyperglycemic effects but shorter anorexia (5–15 min) that, instead of becoming conditioned, disappeared with daily repetition of the injection. I.p. glucose (300 mg/kg) produced a longer anorexia (15–30 min) than i.v. glucose, accompanied by hypoglycemia enduring for 5–20 min. This hypoglycemia was followed by mild hyperglycemia that reached its maximum 10–20 min after the injection, at a time when the anorexia was ending. The repetition of the i.p. glucose caused the disappearance of both the anorexia and the initial hypoglycemic phase. The existence of liver receptors informing the CNS about some variable connected with glucose metabolism was postulated.

Food and water intake of rats after intraperitoneal and subcutaneous administration of glucose, glycerol and sodium lactate.

Abstract Glucose, glycerol and DL — sodium lactate were injected in various doses by intraperitoneal (IP) and subcutaneous (SC) routes in rats accustomed previously to a 24 hr-feeding, 24 hr-fasting schedule. Administration of isosmolar sodium chloride and measurement of water ingestion served as controls for osmotic effects. The three substances determined a dose-dependent feeding depression in the first half hour when administered IP. SC injections produced a much weaker and non dose-dependent feeding depression. Some doses prolonged the hypophagia up to three or even 24 hr. No relation can be established between the hypophagia and the concurrent hyperdipsia since the last effect does not depend on the route of administration. It is suggested that the hypophagia which followed IP administration was due to information of hepatic origin.

Ontogeny of immobility reactions elicited by clamping, bandaging, and maternal transports in rats

Wistar neonate rats assume a characteristic posture when being transported by the mother. This carrying posture is normally elicited by the pressure given by the mothers teeth on the pups neck. By clamping or bandaging the neck and head an immobility reflex with flexion of body and limbs resembling the carrying posture is elicited when pups are in a supine position. On the contrary, by bandaging or by lightly clamping the pups in a prone position, a dorsiflexion with extension of forelimbs is elicited. Both clamping or bandaging inhibits contact and air righting. After a period of immobility bursts of activity follow. The characteristics of all the reactions described above depend on the age of the developing pups. It seems that the immobility reflex with ventroflexion of the body is a behavior used initially by pups to facilitate carrying by the mother, and by both pups and adults as a defense against predators. The posture adopted by the pups bandaged in the neck in a prone position is very similar to the posture they adopt while suckling from the mother. It is postulated that the weight of the mother when lying over the pups plus the pressure on the paws caused by their prone position, could be the stimulus that normally produces the suckling posture.

Some effects of intraperitoneal glucose and of intraportal glucose and adrenaline

Abstract The arterial blood glucose (A) of cats anesthetized with pentobarbital sodium was found to be higher than the portal blood glucose (P). After the intraperitoneal injection of glucose 300 mg/kg, P increased immediately while A decreased or increased much less. That is, the A-P difference, initially positive, became negative after glucose injection and then gradually returned to a positive value. The hepatic vein-portal glucose difference (HV-P) was also positive at the beginning, but became negative after i.p. glucose 300 mg/kg and returned to a positive value after 10–35 min. This corresponds quite closely to the duration of the anorexia observed previously after this dose of glucose in unanesthetized cats and dogs. Therefore, the period of anorexia corresponds to the period of glucose uptake by the liver. The intraportal injection of small doses of glucose (1–10 mg/kg) produced a sizeable hypoglycemia in the arterial blood in the majority of the experiments, while the same dose injected intravenously did not. Intraportal adrenaline in minute doses (0.001–0.5μg/Ag) also produced hypoglycemia. All these facts agree with the hypothesis that liver has glucoreceptors which intervene in the control of blood glucose and food-intake.

Hepatic chromaffin cells

Abstract Chromaffin cells were identified in the liver of mouse, rat, and rabbit. They are found in portal areas, sinusoid walls, or below the connective capsule. The histochemical technique which was used permited to differentiate them from enterochromaffin and mast cells. Liver chromaffin cells could be important for the adrenergic-induced hepatic glucose output.

Anorexia elicited by different catecholamines in rats.

Adrenaline (A) produces a strong anorexic effect, possibly by acting on hepatic receptors (nerve endings on hepatocytes). To study whether this is mediated by alpha- or beta-adrenergic mechanisms, or both, the anorexigenic effects of intraperitoneal injections of A, noradrenaline (NA) and isoproterenol (I) were studied under four different experimental conditions: (I) at the beginning of the dark period in rats fed ad libitum, or (II) on a 24 h-feeding/24 h-fasting schedule; (III) during the light period, under the same feeding schedule; (IV) after an acute 24 h fast. In condition I, the three catecholamines produced a marked decrease in feeding, slightly larger for A. In condition II (dark), they elicited a decrease in food intake about double that in condition III (light), their relative potencies also differed: A greater than I greater than NA in II and A greater than I = NA in III. In IV, the same relative potencies were obtained as in III. A mixture of half-doses of NA and I had the same effect in III and IV as either NA or I alone, suggesting that the alpha and beta effects are additive. However, even a mixture of the full doses of NA and I was not as effective as A in condition IV. This suggests that A is more potent than NA or I at stimulating hepatic adrenergic receptors that cannot be classified as either alpha or beta.

Coding of Metabolic Information by Hepatic Glucoreceptors

Most authors in the field of feeding behavior have adopted the point of view that the control of food intake is “multifactorial” (Adolph, 1943, 1947; Stellar 1954; Brobeck, 1960; Stevenson, 1964). In our opinion this only reflects our lack of knowledge about the main factor controlling hunger and satiety, and a certain misunderstanding about the operation of regulatory systems.

Ontogeny of the endorphinergic and dopaminergic modulation on the immobility reflex elicited by clamping in rats

The effects of some dopaminergic and endorphinergic agonists and antagonists on the immobility reflex (IR) elicited by clamping the neck of the rat were investigated. We found that both morphine and haloperidol produce a significant increase in the duration of this IR at all ages tested (10, 20 and 300 days). The effect of apomorphine depends on the age of the rat, showing an increase in the duration of the immobility reflex only at the age of 10 days which was not counteracted by haloperidol. Naloxone alone showed a slight non-significant tendency to increase the duration of the IR but blocked morphine effects at all ages tested. When naloxone was added to apomorphine there was a peculiar effect: the duration of the immobility reflex was increased significantly in rats of 20 days and adults, but not in 10-day-old rats. The combination of morphine plus haloperidol showed the most marked potentiation of the immobility reflex at all ages tested. These results are discussed with respect to the development of dopaminergic and endorphinergic systems to control posture and movement during the IR, and its possible relation to the catatonia of schizophrenics. A hypothetical model explaining an interaction between the dopaminergic and endorphinergic systems in developing and adult rats is presented.