Amylin and insulin interact to reduce food intake in rats.

We investigated the hypothesis that amylin and insulin, hormones co-secreted by pancreatic B-cells in response to a nutrient stimulus, interact to reduce food intake. A paradigm was employed that assessed food intake in adult male rats after bolus intravenous (i.v.) infusion at dark onset. In one experiment, rats received saline or amylin (0.1, 0.5 or 1.0 nmol). All amylin doses significantly suppressed 1 h intake, and although significant decreases in cumulative intake persisted for 2 h after 0.5 and 1.0 nmol, a significant increase of food intake actually occurred relative to saline during the interval from 1 to 2 h post-infusion. In another experiment, rats received saline, 0.25 nmol amylin, 10 mU insulin, or the combination of amylin plus insulin. Neither amylin nor insulin alone significantly changed cumulative food intake at any time point as compared to saline. However, the combination significantly reduced intake relative not only to saline but also to amylin and insulin alone after 1, 2, and 4 hours. These data are consistent with the hypothesis that endogenous amylin and insulin interact to reduce food intake and, ultimately, body weight.     

Plasma insulin response and food intake in pseudopregnant rats

1. Plasma insulin response to an intravenous glucose injection was measured in anaesthetised pseudopregnant and non-pregnant rats. Food intakes and body composition were also compared in pseudopregnant and non-pregnant animals. 2. The insulin responses and food intakes were greater in the pseudopregnant group. 3. Pseudopregnancy increased the fat-free dry weight of the animals and there was a tendency for the proportion of fat to be increased. 4. The results provide further evidence to indicate that in the rat progesterone plays a significant part in increasing insulin secretion during pregnancy.     

Effect of insulin and 2-deoxy-d-glucose on the food intake of infant rats

The effects of glucoprivation on the food intake have been determined in infant rats up to weaning. It was found that insulin reduced the milk intake of 9, 13 and 17-day-old males and females for three hours after treatment. In 24-day-old pups food intake increased for three hours after insulin administration, and decreased during the next 21-hour period. 2-deoxy-D-glucose increased the food intake in 28-day-old rat pups only. It was concluded that the inability of rat pups to correct glucoprivation by a subsequent increase of food intake is a consequence of the inadequate development of hypothalamic regulatory mechanisms. Glucoprivation stimuli are ineffective inducers of short-term hyperphagia of rat pups until the age of 24-28 days.     

Enhanced food and water intake in renin transgenic rats.

In short term experiments angiotensin II (Ang II) is a potent stimulant of thirst, however it is not known whether prolonged activation of the renin-angiotensin system is associated with chronic alteration of water or food intake. Renin transgenic rats TGRmRen(2)27 (TGR) exhibit significant elevation of AngII in the brain regions involved in regulation of body fluid balance. The purpose of the present study was to find out whether TGR rats manifest also different water (WI) and food (FI) intake and renal excretory functions in comparison to their parent Sprague Dawley (SD) strain. To this end 24 h WI and FI as well as urine excretion (Vu) and urinary outputs of solutes (Cosm), sodium (UNaV) and potassium (UKV) were compared under baseline conditions in 16 TGR and 15 SD rats having free access to water and food. In 15 TGR and 17 SD rats effect of 24 h dehydration on water intake was investigated. Under baseline conditions TGR rats consumed significantly greater amount of food and water than SD rats. Vu, UNaV and UKV were not significantly different in both strains. Cumulative water intakes in SD and TGR rats subjected to 24 h dehydration did not differ. The results reveal that under baseline conditions TGR rats manifest greater food and water intakes than SD rats whereas stimulation of thirst by water deprivation is similar in both strains. The results suggest that the ingestive behavior may be chronically altered by upregulation of the renin-angiotensin system.     

Bombesin reduces food intake of normal and hypothalamically obese rats and lowers body weight when given chronically

Bombesin is a peptide hormone reported to reduce meal size when administered in rats. In the first experiment, synthetic bombesin was injected subcutaneously into normal rats and obese rats with lesions of the ventromedial hypothalamus just prior to the presentation of food. A dose-dependent suppression of meal size occurred for both groups, showing that the peptide has this action in obese as well as normal animals. In a second experiment, a conditioned taste aversion was not formed with a dose of bombesin which suppressed meal size by approximately 50% while the animals did develop an aversion with a dose of LiCl reported to reduce meal size equivalently. In a third experiment, rats were placed on a feeding schedule where they received three 30-min meals each day. After weights had stabilized under this paradigm, bombesin was administered just prior to each meal for six days. The bombesin caused a consistent suppression of meal size when the animals were allowed 30-min meals such that the rats lost weight over the six-day period. When this experiment was repeated with 60-min meals apparent tolerance developed to these actions of bombesin.     

Litorin suppresses food intake in rats

Litorin (LIT), a bombesin-like nonapeptide, decreased food intake in rats in a dose-related manner after parenteral injection. LIT decreased deprivation-induced water intake only at a dose much higher than required to suppress feeding. LIT administration did not significantly alter the frequency of observed feeding-associated behaviors, nor did it result in subsequent aversion to an associated novel solution. Litorin shares with bombesin structural features and pharmacological actions that include the suppression of food intake in a manner that mimics natural satiation.     

Synergistic stimulation of food intake by simultaneous insulin and cold

Insulin administered to rats during simultaneous exposure to cold increases food intake by more than the sum of the separate feeding responses and prevents the normal cold-induced loss of body weight. On withdrawal of insulin with cold maintained, all the body weight maintained by insulin is immediately lost and body weight thereafter is identical to that of rats exposed to cold only. Accumulated food intake for the joint treatment and after withdrawal of insulin with cold maintained is greater than for cold exposure only. There is no increase in metabolic cost due to insulin. Energy density of weight gain during insulin treatment is high and of weight loss on withdrawal of insulin with cold maintained is very low. These responses do not conform with commonly proposed models of feeding control.     

Effects of somatostatin on food intake in rats

We examined the possibility that somatostatin, a tetradecapeptide distributed in the gut and the central nervous system, may influence food intake and behavior in rats. Although intravenously infused somatostatin did not alter food intake in 8 hour fasted rats, intracerebroventricularly infused somatostatin resulted in a biphasic response, first increasing then decreasing food intake. We also observed that the effects of somatostatin vary depending upon whether animals are fed or fasted. In fed rats, food intake was decreased, while in fasted rats food intake was increased. These results suggest that somatostatin can act in the central nervous system to stimulate appetite; but that other factors, possibly related to gut motility or clearance, may inhibit further feeding once the stomach is full.     

Diltiazem enhances food intake and gastrointestinal function in rats

The present study was to investigate the effects of diltiazem, a ghrelin receptor agonist, on food intake and gastrointestinal functions in rats. Rats were intragastrically administered with diltiazem solution (daily 16 mg/kg, 30 mg/kg or 80 mg/kg, 30 d), and the rats with saline as control. To detect the effects of diltiazem on food intake and body weight, the average daily food intake and body weight were recorded, and the serum metabolic hormones of plasma growth hormone (GH) and neuropeptide Y (NPY) were tested by radioimmunoassay. By means of the spectrophotometer and the modified Mett's method, the effects of diltiazem on rat's gastrointestinal function and pepsin activity were tested, respectively. In addition, the gastric juice's acidity of rats was detected by titration and the secretion amount was calculated. The results showed that the food intake and body weight were maximally promoted by diltiazem at the dose of 30 mg/kg daily (30 d). The average daily food intake and body weight were significantly increased, and the serum concentrations of GH and NPY were also remarkably increased in diltiazem-treated groups compared with those in control group. The results also showed that the gastric emptying rate, gastric acid secretion and the activity of pepsin were significantly increased in diltiazem-treated group compared with those in control group. These results suggest that diltiazem induces enhancement of eating, in the same time, it can also stimulate the gastrointestinal function and regulate growth of rat.     

Bombesin stimulates insulin secretion and reduces food intake in the baboon

Baboons received a 5-minute intravenous infusion of either saline or bombesin (BBS; 1-4 micrograms/kg) following 3 1/2 or 16 1/2 hours of food deprivation and were then allowed to eat for 30 minutes. Plasma insulin was significantly elevated following five minutes of BBS infusion, but there was no change of plasma glucose over the same interval. Bombesin infusion resulted in a dose-dependent decrease of food intake that was independent of deprivation time. Plasma insulin levels following the 30-minute meal were significantly depressed after BBS infusions such that there was essentially no change of plasma insulin over the duration of the meal, even though the baboons did not totally suppress their food intake. Following 3 1/2 hours food deprivation, BBS suppressed the post-prandial rise of plasma glucose in a dose-dependent manner. The results provide further evidence that BBS and/or structurally-related peptides are involved in the regulation of feeding and metabolism.     

Intracerebroventricular beta-endorphin increases food intake of rats

B-Endorphin (B-END), met-enkepalin (M-ENK), and DAla²NMe⁵-met-enkephalinamide were administered intracerebroventricularly to rats and effects on the ingestion of a liquid diet were examined. B-END significantly increased food intake in a half-hour test at a dose of 200 ng/rat. Lower or higher doses did not affect food intake. Neither M-ENK or the synthetic enkephalin analog affected ingestion of the liquid diet. These findings demonstrate rapid action of an endorphin on food intake administered at a lower dose than has previously been reported and suggest a specificity for B-END in the endorphinergically mediated hyperphagic response.     

Amylin receptor blockade stimulates food intake in rats

Amylin is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and regulate energy reserves. Amylin potently reduces food intake, body weight, and adiposity when administered systemically or into the brain. Whether selective blockade of endogenous amylin action increases food intake and adiposity remains to be clearly established. In the present study, the amylin receptor antagonist acetyl-[Asn(30), Tyr(32)] sCT-(8-32) (AC187) was used to assess whether action of endogenous amylin is essential for normal satiation to occur. Non-food-deprived rats received a 3- to 4-h intravenous infusion of AC187 (60-2,000 pmol.kg(-1).min(-1)), either alone or coadministered with a 3-h intravenous infusion of amylin (2.5 or 5 pmol.kg(-1).min(-1)) or a 2-h intragastric infusion of an elemental liquid diet (4 kcal/h). Infusions began just before dark onset. Food intake and meal patterns during the first 4 h of the dark period were determined from continuous computer recordings of changes in food bowl weight. Amylin inhibited food intake by approximately 50%, and AC187 attenuated this response by approximately 50%. AC187 dose-dependently stimulated food intake (maximal increases from 76 to 171%), whether administered alone or with an intragastric infusion of liquid diet. Amylin reduced mean meal size and meal frequency, AC187 attenuated these responses, and AC187 administration alone increased mean meal size and meal frequency. These results support the hypothesis that endogenous amylin plays an essential role in reducing meal size and increasing the postmeal interval of satiety.     

The course of infection in rats given small primary doses of Strongyloides ratti and S. venezuelensis

Development of exact doses (less than 100) of Strongyloides venezuelensis third-stage larvae in adult Wistar rats was insignificant (mean proportion of 0.076 of the dose at day 8, n = 16) compared with a homogonic strain of S. ratti (0.538, n = 6; 0.726, n = 6) and heterogonic S. ratti (0.681, n = 6). Newly-weaned Wistars allowed development of a mean proportion of S. venezuelensis of 0.298 (n = 4) compared with 0.013 (n = 4) of the same sample of larvae in adult hosts. Experiments with 75Se-labelled larvae established that S. venezuelensis effectively failed to migrate from skin to intestine in adult animals, while mean proportions of 0.141 (n = 5) and 0.138 (n = 4) of the label was found in the intestines of newly-weaned rats 72 h after skin application. Labelled larvae of homogonic S. ratti migrated equally well in both age groups of host (0.350 and 0.358 in 12- and 3-week-olds respectively). Adult S. venezuelensis transferred surgically to the intestines of previously uninfected full-grown Wistars survived over a 21-day period to the same extent as either strain of S. ratti. Resistance of Wistar rats to S. venezuelensis therefore appears to affect the migratory stage preferentially. S. venezuelensis developed better in mature PVG inbred rats (mean = 0.301, n = 20). Studies of S. ratti showed that infections of both strains initiated by exact (less than 100) doses in Wistar rats had decayed to insignificance between days 26 and 32. The rate of loss of adults of the heterogonic strain was significantly greater than that for the homogonic. The egg content of worms declined as infection progressed and rats were idiosyncratic in their influence on parasite reproduction from the earliest time of sampling (8 d). It was established that 'autoinfection' was an unlikely feature of the biology of homogonic S. ratti following the surgical transfer of 450 first-stage larvae to the intestines of 8 adult Wistar rats. No evidence of infection appeared in the guts of these animals 8 days post-transfer. The significance of these results in terms of the biology of Strongyloides spp. naturally occurring in the rat is discussed.