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Biomedical subjects

D Novin

Publications and source records attributed to D Novin.

At least 37 records · Page 2Linked to original sources

Lateral hypothalamic mediation of hypergastrinemia induced by intracisternal bombesin.

Electrolytic lesions of the lateral hypothalamus (LH), but not of the lateral thalamus, prevented the elevation of serum gastrin induced by intracisternal injection of bombesin in rats. Knife cuts through the lateral or the posterior LH border largely abolished the rise in circulating gastrin induced by intracisternal bombesin. Cuts through the medial LH border partly inhibited the response, whereas cuts through the anterior LH border did not modify peptide action. None of the transections altered basal gastrin levels nor the rise in gastric pH and inhibition of gastric acid output induced by intracisternal bombesin. LH lesions did not modify the rise in serum gastrin induced by intravenous bombesin. These results demonstrate that the gastrin-releasing effect of intracisternal bombesin requires the integrity of fibers crossing the posterior, lateral, and medial borders of the LH and is independent of changes in gastric pH. The LH area is not itself necessary for the expression of the inhibitory action of bombesin on gastric acid secretion.

Animals

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.

Afferent Pathways

The integration of visceral information in the control of feeding.

Electrophysiological evidence exists for sensitivity to many aspects of nutrient depletion and repletion at all levels of the viscera and beyond. Behavioral evidence suggests that feeding is sensitive to manipulations at all of these levels, while at the same time showing that no one site or nutrient is required for feeding regulation. This suggests that one must look at the sequence and interdependence of events occurring from ingestion to ultimate tissue distribution in order to understand the control of food intake.

Animals

Gastric mucosal damage induced by lateral hypothalamic lesions in rats: the potential contribution of bile.

The present study was conducted to investigate the potential contribution of bile to gastric mucosal damage induced by lesions of the lateral hypothalamic area in rats. In two separate experiments it was found that (1) lateral hypothalamic lesions did not alter the rate of bile flow in the acute preparation, but (2) bile duct ligation significantly reduced the incidence of gastric mucosal damage. Based on these and previous findings it is suggested that the reflux of bile interacts with the weakened gastric mucosal barrier to elicit ulceration.

Animals

Stimulation of gastric secretion by acute lateral hypothalamic lesions and its reversal by intracisternal injection of bombesin.

Lateral hypothalamic (LH) but not lateral thalamic (LT) electrolytic lesions markedly increased gastric secretion (volume and acidity) in rats within 2 h of production of the lesions and pylorus ligation. Intracisternal injection of bombesin inhibited gastric secretion (volume and acidity) and reduced to control levels the enhanced acid output produced by the LH lesions. These data demonstrate that acute LH lesions stimulate gastric secretion, and that bombesin exerts a potent gastric antisecretory influence, probably through interaction with LH-related stimulatory pathways.

Animals

Sugar infusion can enhance feeding.

An investigation was made of the role of glucose in the regulation of hunger and satiety in the rabbit. Glucose, when infused intraduodenally at a low rate (1 milliliter per minute), produced a decrease in food intake. However, when glucose was infused into the duodenum at a high rate (3 milliliters per minute), the rabbits nearly doubled their food intake during the first half-hour after infusion. It is hypothesized that the rapid arrival and glucose in the duodenum may produce hunger.

Animals

Intracerebral 6-hydroxydopamine produces extensive damage to the blood-brain barrier in rats.

Extensive extravasation of intravenously administered horseradish peroxidase (HRP) was observed in rat brains infused intranigrally with 8 microgram/4 microliter or 4 microgram/2 microliter 6-hydroxydopamine (6-OHDA), suggesting that the cytotoxin produced widespread alterations in the integrity of the blood-brain barrier. Such damage was dose-dependent and occurred in the mesencephalon around the cannula tip, along the cannula tract, and in the cerebral cortex. The extent of HRP extravasation diminished as a function of increasing time after 6-OHDA administration. These findings indicate that alterations in blood-brain barrier permeability may contribute to the constellation of dysfunctions and possible recovery of function following intranigral infusions of the cytotoxin.

Animals

Hepatic vagotomy (partial hepatic denervation) does not alter ingestive responses to metabolic changes.

The effects of transecting the hepatic branch of the vagus nerve were studied in male and female Long Evans rats. No differences between same-sex hepatic vagotomized (HV) and sham operated (SHM) animals were found in postoperative body weight, diurnal patterns of ingestion, or the response to insulin (4, 8, 12 U/kg, IP), 2-deoxy-D-glucose (125, 250, 500 mg/kg, IP), sodium chloride (10 ml/kg: 0.5, 1.0, 2.0 M, IP), or polyethylene glycol (10 ml/kg: 30% w/v, SC). These results can be interpreted as evidence for a minor role of the hepatic vagus in the total complement of hepatic afferent innervation.

Animals

Celiac vagotomy attenuates the ingestive responses to epinephrine and hypertonic saline but not insulin, 2-deoxy-D-glucose, or polyethylene glycol.

The ingestive responses of rats given celiac vagotomy (C), combined celiac and hepatic vagotomy (CH), or low total vagotomy (removal of all tissue from around the esophagus, stomach and duodenum; LT) were compared with sham operated controls (S) in a series of regulatory challenges. The vagotomized groups responded normally to 2-deoxy-D-glucose (2DG; 125, 250, 500 mg/kg, IP), insulin (4, 8, 12 U/kg, IP), and polyethylene glycol (10 ml/kg: 30% w/v, SC), but displayed attenuated responses to epinephrine (40, 80, 120 micrograms/kg, IP) and hypertonic saline (10 ml/kg: 0.25, 0.5, 1.0 M, IP). These results can be interpreted as evidence that the celiac vagus carries a major component of hepatic afferent innervation. Additionally, when considered with other findings they suggest that whereas the anorectic activity of epinephrine is mostly confined to the liver, 2DG hyperphagia involves stimulation of a wider population of peripheral metabolic receptors.

Animals

Effects of hepatic denervation on the anorexic response to epinephrine, amphetamine, and lithium chloride: a behavioral identification of glucostatic afferents.

Intraperitoneal injections of epinephrine (20, 40, 80, and 160 microgram/kg) and amphetamine (.1, .2, and .4 mg/kg) were administered to rats with various forms of hepatic denervation. In Experiment 1, destruction of the esophageal trunks of the vagus attenuated epinephrine and amphetamine anorexia, but destruction of the hepatic vagus did not. In Experiment 2, rats with celiac ganglionectomy, subdiaphragmatic vagotomy, or the combined operation all exhibited decreased epinephrine anorexia to the same extent. However, ganglionectomized rats were less responsive to amphetamine anorexia than were vagotomized ones. Vagotomized rats were significantly more reactive to lithium chloride (10, 20, and 30 mg/kg) than were controls. These results suggest that the major component of hepatic metabolic afferent fibers travels from the liver, through the celiac ganglion, and into the esophageal vagal trunks where they ascend to the brain. The anorexic action of amphetamine appears to result from a centrally induced sympathetic action on the liver.

Afferent Pathways

Amygdaloid lesions impair ingestive responses to 2-deoxy-D-glucose but not insulin.

Bilateral lesions of the amygdala in male rats impaired the feeding response to 2-deoxy-D-glucose (2-DG; 100, 200, and 400 mg/kg). During the first 3 h postinjection, control rats displayed a dose-related increase in both food and water consumption. Rats with amygdaloid lesions did not respond to 2-DG until the 3rd h postinjection, when only the two largest doses significantly increased food consumption. Their water intake remained unaffected throughout the 3-h postinjection period. During the 4th-24th h post-2-DG administration, both groups displayed a dose-related suppression of food and water intake. Following insulin (10 U/kg), amygdaloid and control animals were indistinguishable: both groups showed a significant short-term increase in food and water intake followed by a reduction in intakes during the 4th-24th h. Central visceral pathways that are important for the ingestive responses to 2-DG may be interrupted by amygdaloid lesions. However, pathways responsible for the ingestive behavior induced by insulin appear unaffected by damage to the amygdala.

Amygdala

Obesity-inducing hypothalamic knife cuts: effects on lipolysis and blood insulin levels.

The effect of two experimental manipulations designed to mobilize lipids from adipose tissue have been investigated in rats with parasagittal knife cuts in the ventromedial hypothalamus (VMH). Those animals which displayed hyperphagia during the initial 5 days VMH knife cuts were then restricted in food intake to reduce body weights to levels comparable to that of the sham-operated controls. Two weeks following the knife-cut lesions, or sham operations, animals in the first experiment were exposed to the cold for 60 min, and those in the second experiment were injected with 2-deoxy-D-glucose (2-DG). The injections of 2-DG increased the level of glycerol in the control animals but not in the animals with VMH knife cuts. Both groups showed a rise in glucose. Plasma insulin and triglycerides were the same in both groups. Exposure to the cold increased the level of glycerol in both groups. The insulin levels were lower in the corresponding groups with knife cuts. These studies show that VMH knife cuts do not produce hyperinsulinemia in pair-gained rats.

Animals

Unimpaired quinine metabolism in rats with ventromedial hypothalamic lesions.

Rats with lesions of the ventromedial hypothalamus (VMH) show a greater decrease in food intake than normal rats if fed diets adulterated with quinine. To determine if this hyperresponsivity is due to impaired quinine metabolism, in vitro rates of drug metabolism of female hooded rats with VMH lesions were measured. Determinations were made both under basal conditions and under conditions known to cause induction of drug metabolizing enzymes. VMH rats showed rates of drug metabolism virtually identical to controls under all conditions tested. These data suggest that VMH lesioned rats are not more sensitive to quinine dietary adulteration because of impaired quinine metabolism.

Animals