N.S. Hell

Metabolic consequences of food restriction in rats

Abstract Some aspects of carbohydrate metabolism were studied in rats subjected to food restriction (single daily meal offered during two hours, either diurnal or nocturnal) for a week. Nocturnal preference for the nocturnal meal was patent in spite of food restriction, inasmuch as the rats fed from 8:00 to 10:00 p.m. ingested significantly more than those fed from 8:00 to 10:00 a.m. The amount of food ingested by rats of both groups was lower than that ingested by the animals with free access to food (as evaluated in 24 hours); nevertheless, both food-restricted groups did not lose weight for the duration of the experiments. The more prominent carbohydrate metabolic adaptations to food-restriction were: (1) high hepatic glycogen concentration during the intermeal periods; (2) hyperglycemia in the 12, 14 and 16 hour intermeal periods; (3) insulinemia was lower than in rats having free access to food all day long; (4) gastric emptying was delayed.

Chronic Salt Overload Increases Blood Pressure and Improves Glucose Metabolism Without Changing Insulin Sensitivity

The effect of sodium chloride salt restriction and overload on insulin sensitivity is still an open question. Some authors have shown that NaCl salt restriction increases insulin resistance, whereas others have reported the opposite. In the present study, the objective was to get some more insight on this issue by studying the influence of dietary salt content on glucose uptake in isolated adipocytes. Male Wistar rats were fed from weaning either low (0.15%) or high (7.94%) salt diets. On the 12th week of age, weight and tail-cuff blood pressure were measured, followed 10 days later by an intravenous glucose tolerance test with concomitant insulin determinations. One week later, the rats were killed by decapitation and epididymal adipocytes were obtained for glucose metabolism evaluation. No weight differences were observed between both groups of animals. Blood pressure was significantly higher (P < .001) on salt overloaded rats (146 +/- 11 mm Hg) than on salt restricted ones (115 +/- 5 mm Hg). Dietary salt content did not influence the area under the curve of plasma glucose. Area under the curve of insulin levels was lower (P = .023) on the high than on the low salt diet. A higher (P < .001) glucose uptake in the absence and in the presence of insulin was observed in adipocytes from rats on the high salt diet. The median effective concentration (EC50) from the dose-response curves of glucose uptake was the same on both groups of animals. Glucose oxidation and incorporation into lipids was also enhanced by salt overload. High salt increased insulin receptor density (P < .001). In conclusion, salt overload increased blood pressure, and high and low salt dietary content did not influence insulin sensitivity based on the unchanged EC50 from the in vitro studies. However, insulin-independent glucose uptake, oxidation, and incorporation into lipids were enhanced in adipocytes from rats on the high salt diet. The lower levels of insulin during the glucose tolerance test on salt-loaded animals may be a consequence of the higher insulin-independent glucose uptake in that group.

Metabolic changes caused by irregular-feeding schedule as compared with meal-feeding

In this study rats eating 50% of the quantity of daily food intake observed for free-fed rats were restricted to regular (MF) and irregular intermeal (IF) intervals. Rats which had free access to food (FF) were also included. The experiments were carried out for 1, 2, 3 and 4 weeks. Body weight, daily food intake, stomach fresh weight, blood glucose and free fatty acids (FFA) levels, liver glycogen content and adrenal ascorbic acid were evaluated. The results showed that adaptative metabolic pattern depends on the discipline of the intermeal intervals. Meal-fed rats with a fixed meal time showed better blood glucose maintenance, slower gastric emptying, increased liver glycogen content and lower FFA mobilization during 22-hr fast than the free-fed group. The same amount of food eating by meal-fed rats given randomly in time (IF) promoted a different adaptative metabolic pattern. The results suggest that the regular intermeal period is an important factor for the establishment of the metabolic changes. Therefore, the meal-feeding schedule has to be considered as a particular modality of food restriction.

Responsiveness of Glycogen Catabolism to Adrenergic Agonists During Insulin-Induced Hypoglycemia in Rat Livers

1. Insulin-induced hypoglycemia (IIH) promoted decreased responsiveness of hepatic glycogen catabolism to phenylephrine and isoproterenol, but not to glucagon and cyanide. 2. In addition, glycogen phosphorylase activity and glycogen levels were not affected by IIH. 3. It was concluded that hypoglycemia promoted changes in hepatic responsiveness to adrenergic agonists. 4. However, the ability of the liver to mobilize glycogen was not influenced by hypoglycemia.

Increase of food intake induced by glucagon in the rat

The effect of intraperitoneal administration of saline, glucose (25 mg/100 g b.w.), insulin (0.025 U/100 g b.w.) and glucagon (50 micrograms/kg b.w.) on glycemia, liver glycogen concentration and food intake was studied on 104 male adult Wistar rats. When saline was injected the amount of food ingested was similar to that expected at the metabolic moment selected for the tests. Glucose administration did not reduce food intake but both insulin and glucagon provoked a threefold increase during the 60 minutes ensuing the injection. The overall ingestion of food during the 24 hours after the injection of the hormones was significantly higher (about 10%) than the control values during the preceding or the succeeding 24 hours. A hyperphagic, rather than a hypophagic effect of glucagon administration is possibly related to the small dose used in the experiments. The mechanisms involved in the increase of food intake due to glucagon are discussed in terms of acceleration of the metabolic reactions that normally prevent large drops of glycemia as glucose utilization proceeds during the inter-meal periods and that in physiological conditions build up until the need for food arises.

Effect of Lifelong High- or Low-Salt Intake on Blood Pressure, Left Ventricular Mass and Plasma Insulin in Wistar Rats

Background:Salt restriction is recommended for hypertension treatment to reduce blood pressure, but its effect on some risk factors is still a matter of discussion. The aim of this study was to observe the effect of a long period of salt restriction or overload on blood pressure, left ventricular mass (LVM), kidney mass (KM), glucose tolerance, and plasma insulin. Methods:Male Wistar rats were fed from weaning with a low-salt diet (LSD) or a high-salt diet (HSD) until 72 weeks of age. After 48 weeks, the diets were changed in half of the rats: HSD until 48 weeks and then LSD (LHSD) and LSD until 48 weeks and then HSD (HLSD). Body weight, blood pressure, electrolyte excretion, creatinine clearance, plasma renin activity, LVM, KM, and intravenous glucose tolerance test with insulin determinations were evaluated. Results:Blood pressure, LVM and KM were higher on the HSD than on the LSD. Blood pressure was lower on the LHSD than on the HLSD. There were no differences in LVM and KM on the LHSD compared with the HLSD. The relationship between area under the curve (AUC) of insulin and glucose during the intravenous glucose tolerance test was higher on the LSD. No differences were detected in AUC between the two groups of rats whose diet were inverted with 48 weeks of age. Conclusions:A chronic HSD increases blood pressure, LVM, and KM and a chronic LSD increases plasma insulin in response to a glucose challenge in aging rats. The hypotensive effect of salt restriction is not modified by a previous long period on a HSD.

Carbohydrate metabolism and food intake in food-restricted rats. Relationship between the metabolic events during the meal and the degree of food intake

To study some metabolic features during feeding in food-restricted rats two groups of animals were maintained on a 2 hr feeding/22 hr fast schedule. Group D (n = 38) received a meal every day from 8:00 to 10:00 a.m. Group N (n = 34) was given the meal from 8:00 to 10:00 p.m. The average total amount of food ingested by rats of group N in the two hour period was 6.3 +/- 0.4 whereas Group D ingested 4.8 +/- 0.3 g/100 g b.w. The metabolic pattern also was different in one group as to the other. The basal liver glycogen content when feeding started was considerably lower in the nocturnal group (0.14 +/- 0.02 mg/100 mg of liver tissue) than in the diurnal group (0.44 +/- 0.10 mg/100 mg). Afterwards glycogen increased in both groups but more steeply and intensely in group N. Glycemia increased in group D and was almost invariant in group N. Insulinemia went up in both groups but in group D its peak was higher and occurred 60 minutes after the onset of feeding whereas the peak in group N was much lower and occurred at 90 minutes. There was a clear dissociation between the time courses of insulinemia and glycemia in both groups, especially in group N, which suggests a central control of insulin secretion during feeding that partially unlocks it from blood glucose concentration. The hepatic glycogen content was partially linked to the amount of food ingested but again there was a dissociation between these two variables, inasmuch as a higher glycogen replenishment in the nocturnal group corresponded to a larger food intake.

Influence of the vagus and splanchnic nerves on insulin secretion and glycemia

The role of the autonomic nervous system in control of the acute and the late-phase of insulin secretion was studied in mongrel dogs before and after bilateral severance of the vagus, splanchnic, and vagus plus splanchnic nerves. Glucose-stimulated acute insulin secretion increased after splanchnicotomy or transection of both autonomic nerves but remained unchanged after vagotomy alone. Late-phase insulin secretion was not altered by transection of any of the nerves alone or in combination; similar results were obtained as to fasting insulin levels. In contrast, fasting glycemia was increased after vagotomy and decreased after splanchnicotomy. These findings disclose tonic sympathetic and parasympathetic influences on blood glucose basal concentration and indicate an acute inhibitory role of the sympathetic system on insulin secretion.

Carbohydrate metabolism and food intake in food restricted rats: Effects of an unexpected meal ☆

Abstract Rats subjected to a daily single-meal feeding schedule were presented with an unexpected meal at three different times of the day and the effects on the carbohydrate metabolic patterns were determined. The results indicate that it is the actual metabolic moment of the organism, rather than the duration of the inter-meal period and the degree of gastric emptying, that determines the amount of food ingested.

Reversibility of metabolic changes induced by feeding schedule in rats

This study aimed to investigate the effect of free-feeding on rats kept on meal-feeding schedule for a prolonged period. Thus, rats meal-fed for 4 and 20 weeks were given free access to food for subsequent 5 weeks. The metabolic adaptation of higher hepatic glycogen content, low plasma FFA values and sustained glycemia during 22-hr fast, reported for rats subjected to meal-feeding, completely disappeared after free-eating period. The rate of body weight gain increased as a consequence of the free access to food in both groups but the control values (group with food ad lib all the time) were attained only in rats previously submitted to meal-feeding for the shorter period of time (4 weeks). The findings of this study suggest that the recovery of body weight by meal-fed rats, for the control values, seems to depend on the duration of the meal-feeding schedule and the age when it is imposed.