Donald Novin

Infusion of 2-Deoxy-D-Glucose into the Hepatic-Portal System Causes Eating: Evidence for Peripheral Glucoreceptors

Injections of 2-deoxyglucose into the hepatic-portal system of normal rabbits increased eating to a greater extent and with shorter latency than comparable injections of 2-deoxyglucose into the jugular vein or into the hepaticportal circulation of the vagotomized rabbit. These differences suggest the existence of vagally mediated peripheral glucoreceptors important in the initiation of food intake.

Functional correlations between lateral hypothalamic glucose-sensitive neurons and hepatic portal glucose-sensitive units in rat

The effects of glucose injection into the hepatic portal vein on neural activity of the lateral hypothalamic area (LHA) were studied in rats. A majority of identified glucose-sensitive neurons in the LHA were inhibited by portal injection of glucose. This was found to be mediated through the alpha-noradrenergic pathways. Most of the glucose-insensitive neurons did not respond to the same procedure. Portal injection of hypertonic saline increased neural activity of some glucose-insensitive neurons but no glucose-sensitive neurons responded. Convergence of hepatic vagal afferent glucose-sensitive units on LHA glucose-sensitive neurons was clarified by this study.

Decreased feeding in rats following hepatic-portal infusion of glucagon

Abstract Male rats received a single hepatic-portal injection of glucagon following mild food deprivation. Cumulative food intake measured after 0.5–20 hr was decreased by the hormone. The absence of a concomitant decrease in water intake suggested a specific effect of glucagon on feeding. This specificity was further demonstrated by the use of an hepatic-portal infusion of glucagon as the unconditioned stimulus for the formation of a conditioned taste aversion which failed to produce avoidance of a novel taste. In contrast, pairing the taste with an intraperitoneal injection of lithium chloride did produce a learned taste aversion. Thus, the decreased feeding following infusion of a low concentration of pancreatic glucagon through a chronic hepatic-portal cannula cannot be attributed to visceral malaise. The relatively specific effect of this hormone on short-term feeding probably results from the activation of hepatic glycogenolysis, with the long-term effect on feeding possibly due to gluconeogenesis.

Afferent projections to the dorsal motor nucleus of the vagus

The afferent projections to the dorsal motor nucleus of the vagus (DMN) were investigated by iontophoretically infusing horseradish peroxidase (HRP) into that neural region of the rat. After the tetramethylbenzidine histochemical procedure was performed on the HRP-injected brains, projections to the DMN from several areas were observed including the nucleus reticularis parvocellularis and gigantocellularis, the nucleus of the solitary tract, the nucleus raphe obscuris, the principal sensory trigeminal nucleus, and the paraventricular nucleus of the hypothalamus. The pathway originating in the paraventricular nucleus was the only forebrain projection to the DMN, a finding compatible with observation of other investigators.

The effect of isotonic glucose on eating as a function of feeding condition and infusion site

Abstract Rabbits were infused with 10 cc of 5% glucose and equal volumes of isotonic saline in a free-feeding condition and following a 22-hr total food-deprivation period. Infusions were made into the duodenum or a collecting vein of the hepatic-portal system through chronic indwelling cannulas. The results showed that duodenal infusions of glucose suppressed feeding only in the free-feeding rabbit while hepatic-portal infusions suppressed feeding only in the food-deprived animal. Both suppressive effects of isotonic glucose were eliminated by bilateral, subdiaphragmatic vagotomy. The results suggest that at least two loci can act to reduce eating following glucose intake and the locus of the effect is dependent upon the feeding condition or nutritional state of the animal.

Chronic insulin infusion suppresses food ingestion and body weight gain in Rats

Abstract Rats were implanted with Minipumps delivering 0 to 6 U regular insulin daily. Insulin suppressed food intake by reducing meal size in normal animals and limited weight gain, while in diabetic animals, it lowered plasma glucose, eliminated glycosuria, and promoted a resumption in body weight gain. Insulin appears to amplify the satiety effects of meals in normal animals. In diabetic animals, insulin has no immediate effect on meal parameters if excessive body weight loss has occurred but reduces hyperphagia when prediabetic body weight and nutrient repletion has been approximated.

Conditioned taste aversions: vagal and circulatory mediation of the toxic unconditioned stimulus.

In these experiments we tested the hypothesis that the same afferent systems which mediate vomiting reflexes also participate in conditioned taste aversions which are formed when ingestion of a taste cue is paired with subsequent internal malaise. Borison and Wang have shown that emetic reflexes in dogs and cats are integrated in a brainstem center which responds to local gastric irritation mediated by the vagus or to bloodborne toxins monitored by brain stem chemoreceptors. This same afferent system may mediate taste-illness conditioning since the emetic center is anatomically associated with the relay nucleus for primary taste afferents. We have shown that subdiaphragmatic vagotomy in rats disrupts the acquisition of a saccharin aversion induced by repeated conditioning trials with low doses of intragastric or intraperitoneal copper sulfate. In contrast, there is little effect on the aversion produced by a single, larger dose of copper sulfate injected directly into the blood via the tail vein, although vagotomized rats displayed an accelerated extinction pattern. These results parallel reports on the effect of vagotomy on vomiting reflexes in dogs and suggest a functional relationship between acute vomiting reflexes in dogs and suggest a functional relationship between acute vomiting reflexes which eject poison and chronic conditioned taste aversions which inhibit subsequent ingestion of poison; further, they provide evidence that these responses are subserved, at least in part, by similar neural mechanisms.

Physiological and morphological changes in the gastrointestinal tract induced by hypothalamic intervention: An overview

Neural control and modulation of gastric secretion is well established. The role of the parasympathetic vagal system as a final motor pathway in gastric acid secretion is clearer than the involvement of the sympathetic nervous system. Both portions of the autonomic nervous system, however, appear to play an important role in the pathogenesis of at least experimentally induced gastric erosions. With respect to higher neural control there are numerous reports of hypothalamic effects on gastric secretion, motility, and morphology, yet the results of many of these reports appear equivocal. This ambiguity can be attributed in part to species differences, time course of observations, and differences in stimulation and lesion parameters. However, a mcal description of the sites of central lesions and stimulation. Implications of several of the studies concerning hypothalamic involvement in gastric functions are reviewed and recent methodological advances including neural fiber transection, relatively specific neural cell damage with neurotoxins (e.g., 6-OHDA, kainic acid), histochemistry and intracerebral infusions of gut hormones are suggested as alternative approaches to studying brain-gut relationships.

Duodenal or hepatic-portal glucose perfusion: Evidence for duodenally-based satiety ☆

Abstract Hepatic-portal infusions of glucose solutions of up to 30% concentration had no effect on food intake in free-feeding rabbits. In contrast, similar volumes and concentrations, intra-duodenally perfused, reduced food intake, especially in the first hour postinjection when compared to equal volumes and osmotic concentrations of saline solutions. This duodenally-based suppression of food intake was completely abolished in the recovered, subdiaphragmatically vagotomized rabbit. We propose, therefore, the possibility of vagally-mediated receptors which are activated either directly by nutrients or by the secretions which result from the presence of these nutrients in the duodenum.

Acquisition of learned taste aversion following bilateral subdiaphragmatic vagotomy in rats

Abstract Bilateral subdiaphragmatic vagotomy in rats did not prevent subsequent acquisition of a conditioned taste aversion in a two-bottle preference paradigm. Neither verified-vagotomized nor sham-vagotomized animals shifted their preference when presentation of the preferred fluid was immediately followed by injection of isotonic NaCl, whereas both surgical groups shifted their preference to the initially-nonpreferred fluid when presentation of the initially-preferred fluid was followed by injection of isotonic LiCl. Although these results do not preclude some involvement of vagal innervation in toxiphobia conditioning in combination with other neural systems, they do indicate that the role of the vagus nerves is not a major one.