Postabsorptive hyperinsulinemia in rats with subdiaphragmatic vagotomy

The effects of bilateral subdiaphragmatic vagotomy and of lateral hypothalamic lesions on the acute plasma glucose and insulin responses to liquid and solid meals were studied in female rats. Following recovery of an initial postoperative weight loss, vagotomized rats exhibited an exaggeration of plasma glucose and insulin responses compared to sham-vagotomized animals 17 min after the initiation of a liquid meal (6 ml sweetened milk in 7 min). Vagotomy did not alter basal glucose and insulin levels. The exaggerated postabsorptive response to oral liquid glucose in vagotomized rats was not observed after the consumption of an isocaloric solid meal (1.86 g sucrose pellets in 7 min). Rats with lateral hypothalamic lesions had significantly lower basal glucose and insulin levels, but both the preabsorptive and postabsorptive responses to oral glucose were unaffected by the lesion. The results in vagotomized animals were attributed to enhanced gastric emptying of liquid loads leading to a more rapid absorption of glucose from the intestine, which in turn resulted in an increased insulin response. In humans this is followed by rapid-onset hypoglycemia, and it is hypothesized that the abnormal postabsorptive glucose and insulin responses account in part for the pattern of small, frequent meals observed with vagotomized animals on liquid diets.     

Ontogeny of cephalic insulin release by the rat

Developmental aspects of cephalic insulin release in rats were evaluated by examining insulin secretion in response to the sweet taste of saccharin at different ages. A cephalic insulin response was present at the time of normal weaning (21–22 days) and by 34 days of age its magnitude was indistinguishable from that of adults. The early appearance of cephalic insulin release prompted a second study examining whether this response is present at birth; i.e., prior to any suckling experience. In newborn rat pups, no increase in plasma insulin was seen as a result of introduction of saccharin into the oral cavity. It was concluded that maturational and/or learning changes responsible for cephalic insulin release occur during the suckling period. The discussion concerned whether these changes involve maturation of the afferent loop, the efferent loop and/or learning as a consequence of the suckling experience.     

A nitric oxide synthase inhibitor, L-NAME, attenuates saccharin drinking in a two-choice test in water-deprived rats.

The nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) [0 (veh)], 10, 25, and 50 mg/kg s.c.) was administered to water-deprived, saccharin-preferring, rats in a 30-min two-bottle choice test of 0.1% sodium saccharin and tap water in a within subjects design. Saccharin intake was selectively attenuated in a dose-related manner with increasing dose of L-NAME, reaching statistical significance at 25 and 50 mg/kg L-NAME when compared to vehicle control condition (p < 0.01). In contrast, water intake was not appreciably affected. Total fluid intake was attenuated as well. Neither saccharin nor water intake in a second group of animals was significantly affected by the inactive isomer, D-NAME, suggesting a stereospecific action. These data suggest that a taste factor might contribute to the well-documented hypophagic action of NOS inhibitors in a number of animal species. The possibility that such effect might be mediated through a serotonergic mechanism is considered.     

Conditioned taste avoidance induced by lactose ingestion in adult rats

Because adult rats have very low levels of the intestinal enzyme lactase, the ingestion of appreciable quantities of the disaccharide lactose may cause gastrointestinal distress. The present experiment was designed to demonstrate that adult rats will learn to avoid previously neutral stimuli which have been paired with lactose ingestion. Adult rats ingested both a novel solution [either tap water (WA) or 0.1% saccharin (SA)] and a novel food substance (49% powdered lab chow + 50% added disaccharide + 1% saccharin) during a single conditioning session. The added disaccharide was either sucrose (group SU-SA), lactose (groups HL-SA and HL-WA), or equal amounts of these two disaccharides (group LL-SA); a fifth group (LC-SA) consumed a sucrose-containing diet to which lithium chloride was added (5 mg per 1 g of diet). Separate feeding tests and drinking tests, carried out over several weeks, were used to assess the extent of conditioned taste avoidance. In the four feeding tests, rats were allowed to ingest powdered lab chow with added saccharin (but without added disaccharide), while in the four drinking tests, rats chose between tap water and a 0.1% saccharin solution. Group HL-SA demonstrated a substantial conditioned avoidance in both feeding and drinking tests, but group HL-WA showed avoidance only in feeding tests. Conditioned avoidance was weak in group LL-SA; the strongest avoidance was observed in lithium chloride-treated rats (group LC-SA). Results are related to previous research and to the hypothesis that a learned avoidance of milk may facilitate the weaning process in mammals.     

Profound conditioned taste aversion induced by oral consumption of 2-deoxy-D-glucose

In a previous experiment rats avidly avoided a solution of 2-deoxy-d-glucose in 0.2% saccharin (2-DG+S), drinking less than 1 mL over 3 days. The present study investigated taste avoidance and conditioned taste aversion (CTA) to orally presented 2-DG+S as well as CTA in response to i.p. injections of 2-DG. In Experiment 1, rats were given either a glucose/saccharin(G +S) solution or 2-DG+S for eight 30-s test periods. Four seconds into the first 30-s test, rats in the 2-DG+S group licked significantly less than rats in the G+S group, and licking almost totally ceased in the remaining seven tests. Overnight water intake was not different between the groups, but when offered a G+S solution, rats in the 2-DG+S group almost totally avoided the solution and still showed a significant aversion to G+S when retested 6 days later. In Experiment 2, rats were allowed to drink G +S, and were then injected i.p. with 500 mg 2-DG/kg, 500 mg D-glucose/kg body weight in 0.3 mL water, or with 0.3 mL saline. When tested with a G +S solution the next day, rats in the 2-DG group showed a highly significant avoidance, while rats in the glucose group were not different from those in the saline group. The results of the second experiment are consistent with earlier studies of CTA induced by i.p. injections of 2-DG. The present study indicates that small amounts of orally ingested 2-DG produce a CTA as strong or even stronger than that following injected 2-DG, most likely by inducing malaise. Whether the onset of malaise is fast enough to account for the rapid initial avoidance of this solution or a taste factor is also involved is not yet clear.     

Short-term satiety signals generated by saccharin and glucose solutions

Four groups of rats were deprived of water for 24 hr and first allowed to drink 6 ml either of water, 0.25% saccharin solution, 3% glucose solution, or a mixture of 0.25% saccharin 3% glucose solution, subsequently they were given a 3% glucose solution for 20 min. The glucose solution was given either immediately or 30 min after the intake of 6 ml of the 4 experimental liquids. With immediate presentation the glucose intake was lowest following ingestion of the saccharin-glucose solution, next lowest, following ingestion of the saccharin solution and third lowest, following the glucose solution. The glucose intake was highest following water ingestion. However, with the 30-min delay period the differences dissipated. Saccharin and glucose solutions appear to generate a short-term satiety effect which inhibits subsequent intake of glucose solution.     

Taste aversion in rats induced by forced swimming, voluntary running, forced running, and lithium chloride injection treatments

The present experiment compared the strengths of taste aversion learning in rats induced by forced swimming in a water pool (5, 15, 30, or 60 min), voluntary running in an activity wheel (15, 30, 60, or 120 min), forced running in a motorized wheel (60 min at the speed of 8 m/min), optional running in the apparatus consisting of an activity wheel and a side room (120 min), and a lithium chloride (LiCl, 0.15 M LiCl at 2% of body weight) injection. The rats were given an access to saccharin solution immediately followed by one of the above treatments or simply returned back to the home cages for the control group. On the next 2 days, aversion to the saccharin solution was assessed by two-bottle choice testing between it and tap water. The following results were obtained. (1) The saccharin aversion was a positive function of exercise durations in the forced swimming and voluntary running rats, and the exercise of more than 30 min induced statistically significant saccharin aversion, compared with the control rats. (2) The forced running caused relatively strong saccharin aversion. The group of forced running rats acquired the numerically strongest saccharin aversion on average among all exercised rats. (3) The optional running treatment had little effect. (4) The LiCl injection resulted in the strongest aversion among the all treatments explored here.     

Alterations in ingestive behavior following experimental portacaval anastomosis in rats

Following surgical construction of an end-to-side portacaval shunt (PCS), male rats exhibited exaggerated consumption of glucose, saccharin, saline, and ethanol solutions relative to sham-operated rats in 24-hr preference tests with water present. Spontaneous daily water intake was also increased, but daily food intake and body weight were decreased by PCS. The overconsumption of glucose, saccharin, and saline exhibited by rats with portacaval shunts was reduced, or eliminated, by providing a corn supplement to their diet, consistent with the view that the disturbance of amino acid balance may have contributed to this ingestive abnormality. In a series of short drinking tests, rats with portacaval shunts consumed more of both 10% glucose and 10% fructose (given in separate tests) than sham-operated rats and glucose intake was greater than fructose intake for both of these groups. However, neither surgical nor saccharide condition affected the duration of the first bout or the initial inter-bout interval, indicating that the relative satiating properties of these two monosaccharides were probably not altered by portacaval shunting.     

Thirst and saccharin preference in rats

Three experiments with 112 water-deprived rats initially showed higher water than saccharin consumption regardless of whether the liquids were presented singly or as a choice, and whether food was available or withheld during testing. More saccharin than water was consumed later. The reversal from water to saccharin was positively related to hours of water deprivation and per cent saccharin concentration and occurred with either continuous or interrupted exposure. It was concluded that rats must first drink water in order to reduce their water deficit to some threshold before saccharin is drunk. Postingestional and oral factors then become responsible for ingestion of large quantities of saccharin.     

Complex maze performance in young and aged rats: response to glucose treatment and relationship to blood insulin and glucose.

In aged rats and humans, impaired glucose regulation has been correlated with poor memory performance, and glucose treatment can result in improved performance. We tested this glucose hypothesis with rats in a 14-unit T-maze that has provided robust evidence of age-related performance decline. Aged (24-25 month) and young (6-7 month) male F-344 rats were pretrained for one-way active avoidance before receiving complex maze training (4 daily trials over 5 days) with the contingency of moving through each of 5 segments to avoid footshock. Ten min before daily training, aged rats received either saline or glucose in doses of 10, 100, or 500 mg/kg IP, while young rats received saline. Significant (ps less than 0.05) age-related increases in errors, runtime, and shock duration were observed. Glucose treatment had no significant effect on the number of maze errors committed; however, performance variables such as runtime and shock duration appeared to be reduced in rats receiving glucose. About 4-6 weeks later, a sample of these rats was fasted overnight, injected IP with glucose (150 mg/kg), and bled at various postinjection intervals to obtain estimates of blood glucose and insulin levels. Significant correlations (ps less than 0.05) were observed between maze errors and baseline glucose levels, r(21) = -.62, and peak glucose response, r(19) = .49. However; within the aged group, significant correlations (ps less than 0.01) with maze errors emerged only for baseline glucose, r(13) = -.69, and peak insulin response, r(13) = -.65. Thus, regulation of insulin, but not glucose, appeared related to learning abilities among aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of gonadectomy on taste preference for glucose solutions in rats.

Mature male and female rats maintained on an ad lib diet were given a choice between tap water and glucose solutions of different concentrations (1, 5 and 12 percent). Both sexes exhibited a definite preference for the 12 percent glucose solution, but the females drank significantly more than males. Gonadectomy produced neither quantitative nor qualitative changes in the choice made by male rats. On the contrary, gonadectomized females showed a depression of the 12 percent glucose solution intake and an increase in the 5 percent glucose solution intake, resulting in a decrease of the total fluid intake. A comparison of ovariectomized and intact female rats in regard to the self-selection of tap water and a 5 percent glucose solution confirmed the stimulatory effect of ovariectomy on the 5 percent glucose solution intake. When a choice between tap water and 12 percent glucose solution was permitted the ovariectomized rats showed a weaker positive response to the sweet solution than the intact female rats.     

Increased and decreased preference for saccharin immediately following injections of various agents

Rats pretrained for preference testing and injected with LiCl showed a reduction of saccharin preference in a test with a novel saccharin solution paired with water given 15 min following the injection. Previous exposure to the saccharin solution precluded this selective depression of drinking. In a second experiment, using rats naive to saccharin, insulin injection produced an increase, 2-DG and hypertonic NaCl produced a decrease, and saccharin injection produced no change in saccharin preference.     

Saccharin preferences in food deprived aging rats are altered as a function of perinatal drug exposure

The purpose of this long-term experiment was to determine if perinatal exposure to CNS activating drugs resulted in early and/or altered onset of aging, as measured by changes in preference for preferred concentrations of saccharin solutions. Seventy-nine primiparous Sprague-Dawley rats received twice daily subcutaneous injections of either 3.0 mg/kg or pure nicotine, 5.0 mg/kg of methamphetamine HCL, 5.0 mg/kg of saline vehicle, or no injections during the 21 day gestational period and during days 3–21 of the nursing period. Twelve male offspring were randomly selected from each treatment condition, and at six months of age, they were presented with a choice of 0.20, 0.10, 0.05, 0.025, 0.01, and 0.005% of saccharin in a tap water solution and plain tap water at three month intervals. Each concentration was paired with water and presented for a 48 hr period. Eight sessions were analyzed, which spanned the ages of 15/36 months. Multivariate analyses revealed that: (1) The preference for individual saccharin concentrations across time differed as a result of maternal treatment. Differences were primarily due to the drug treatments and not to injection, (2) The pattern of saccharin preference changed over time as a function of maternal treatment but the overall level of saccharin consumption was not affected. These shifts were due to the drug treatments, not injection per se, (3) The total amount of saccharin solution consumed over time did not differ significantly among treatments, (4) The total amount of fluid consumed over the mature lifespan (saccharin solution plus water) decreased for all rats irrespective of maternal treatment. Other differences over time in total fluid consumption paralleled the saccharin index measures described above. Thus, perinatal treatment had a lasting effect upon preference for nonnutritive sweet solutions. The significance of this for aging organisms is discussed.     

Feeding inhibition and death produced by glucose ingestion in the rat

The ingestion of a 7% or 8% glucose solution by normal rats maintained on a one hr/day feeding schedule significantly suppressed food intake and body weight, and resulted in death. A 3.5% glucose solution did not have these effects, while a 21% glucose solution resulted in greater feeding and weight suppression, but no fatalities. The addition of saccharin to the glucose solutions enhanced their suppressive effects, although saccharin by itself did not reduce food intake or body weight. The results indicate that caloric depletion is not the sole cause of glucose-induced death, and some other factor(s), perhaps insulin hypersecretion, must also be responsible for this unusual effect.     

Abnormalities of carbohydrate metabolism in spontaneously hypertensive rats

Summary The present study was performed to investigate as to whether peripheral insulin resistance exists in spontaneously hypertensive rats (SHR). After a 12 h fasting period, SHR had significantly higher serum glucose and higher plasma glucagon values in comparison to normotensive control rats (WKY). There was a tendency for higher serum insulin concentrations as well, but this difference did not reach significance. After oral glucose loading or glucose/insulin administration, serum glucose and insulin levels were also higher in SHR compared to WKY rats. Muscle glycogen and glucose concentrations were identical in fasted SHR and WKY rats. With an oral glucose load or glucose/insulin treatment there was a significant increase in muscle glycogen, whereas glucose values declined in skeletal muscle. Both total (a+b-form) phosphorylase activity as well as the active a-form of the enzyme were similar in skeletal muscle of SHR and WKY rats. Glucose/insulin administration or oral glucose loading induced a considerable reduction of both a+b-form and a-form activities. The decrease in muscle phosphorylase activities was almost identical in both groups of animals. There was also a comparable activity of muscle glycogen synthetase activity in all groups of rats. Despite subtile changes of glucose, glucagon and to a lesser degree insulin levels which would be suggestive of insulin resistance, the data obtained from skeletal muscle argue against peripheral insulin resistance in spontaneously hypertensive rats.     

脂质灌注对大鼠血浆抵抗素和ghrelin的影响*

目的：探讨脂质灌注对大鼠血浆抵抗素和ghrelin的影响。 方法： 采用正糖钳夹技术，在钳夹前后分别测定生理盐水对照组和脂质灌注组血浆抵抗素和ghrelin浓度，并用［3H］-葡萄糖作为示踪剂测定外周组织和肝糖的代谢。 结果： 脂质灌注组大鼠血浆游离脂肪酸（FFA）明显增加（P<0.01），葡萄糖输注率（GIR）明显降低（P<0.01）。对照组肝糖产率（HGP）明显被抑制（88%）。脂质输注组胰岛素对HGP的抑制作用明显减弱。在钳夹期间，脂质组与对照组比葡萄糖清除率（GRd）轻度降低。在正糖钳夹术结束时，对照组血浆ghrelin水平与钳夹前相比明显降低(P<0.05)。4 h的脂质灌注也引起了血浆ghrelin浓度的明显下降(P<0.05)，但是在钳夹结束时和对照组比没有明显差异。相关性分析表明空腹血浆ghrelin水平与空腹胰岛素和血糖呈明显负相关（r=-0.52和r=-0.61, P<0.05）。脂质灌注后大鼠血浆抵抗素水平较灌注前和对照组明显升高（P<0.01），空腹血浆抵抗素浓度与空腹FFA（r=0.68, P<0.01）、血糖（r=0.66, P<0.01）呈明显正相关。 结论： 脂质灌注诱导了肝脏和外周的胰岛素抵抗，抵抗素在胰岛素抵抗的形成中可能具有重要作用。高胰岛素血症，而不是游离脂肪酸，降低了大鼠循环ghrelin水平。     

ACTH and corticosterone secretion following insulin in intact and in variously hypothalamic deafferentated male rats

Summary Adult male rats, intact (N) or with posterior (PHD), anterior (AHD) or complete (CHD) hypothalamic deafferentations, were injected with either 0.04 or 0.2 u/100 g b.wt. of insulin. Forty-five minutes later they were decapitated and trunk blood was collected for serum glucose, adrenocorticotropic hormone (ACTH) and corticosterone (CS) determinations. The high insulin dose reduced serum glucose by approximately 50% and elicited a marked increase in serum ACTH and CS levels in all groups of animals as compared to the vehicle-treated group. In contrast, the low insulin dose which reduced serum glucose approximately 30% elicited a significant adrenocortical response only in the intact or PHD groups but failed to stimulate this response in animals with CHD or AHD. These results demonstrate that (1) CNS sites, outside the medial basal hypothalamus (MBH), mediate the adrenocortical response during the initial stages of hypoglycemia by a neural pathway impinging upon the CRF neurons from the rostral direction, and (2) the adrenocortical response during the more enhanced hypoglycemia stages is mediated by a systemic mechanism which acts directly on the MBH.Abbreviation u units of insulin     

Effects of T-2 toxin on saccharin aversion and food consumption in adult rats

The present experiment used a saccharin aversion paradigm to evaluate the potential aversive action of T-2 toxin, a trichothecene mycotoxin that induces emesis and weight loss. Adult male rats were fed either a control diet or a diet adulterated with 640 ppm lithium chloride (positive control) or with 2.5, 5.0 or 10.0 ppm T-2 toxin and given access to a 0.1% saccharin solution and to tap water during four training days. The rats were then shifted to the control diet during three extinction days. Moderate saccharin aversion induced by the positive control diet and the 5.0 and 10.0 ppm T-2 diets was apparent on the third day of exposure and the aversion to the saccharin solution abated during the extinction trials. Saccharin aversion was evident at levels of T-2 toxin that did not induce obvious tissue pathology.     

Saccharin pre‐exposure enhances appetitive flavor learning in pre‐weanling rats

In adult rats, data suggest that consumption of sweet tastes that do not deliver anticipated caloric consequences using high‐intensity, non‐caloric sweeteners, such as saccharin, interferes with learned relations that may contribute to energy balance. The goal of the present study was to assess the development of learning about sweet taste and calories by assessing whether pre‐exposure to saccharin solutions reduces cue competition in pre‐weanling rats. The results demonstrated that rats pre‐exposed to saccharin and then trained with a novel grape flavor paired with a glucose‐sweetened solution consumed more of the novel grape flavor presented alone than rats that had been pre‐exposed to saccharin and given the grape flavor paired with water alone. No differences in intake of the novel grape flavor were observed in groups given pre‐exposure to water or glucose solutions. Thus, by 15 days of age, rats appear to have established an association between sweet tastes and calories, and this association can be weakened by exposure to saccharin. © 2012 Wiley Periodicals,Inc. Dev Psychobiol 54: 818–824, 2012     

术前碳水化合物对瘢痕切除术后胰岛素抵抗的影响

目的观察术前口服碳水化合物及静脉输注葡萄糖对术后胰岛素抵抗程度的影响.方法择期瘢痕切除术病人60例,随机分为对照组、口服组和静注组,每组20例.术前对照组常规禁食禁饮;口服组口服12.5%碳水化合物的饮料（CHO）;静注组持续静脉输注10%葡萄糖液.分别于口服或静注前、术后6 h采血,测定血糖、血清胰岛素以及红细胞胰岛素受体.结果处理前各组血糖、血清胰岛素、胰岛素敏感指数及红细胞胰岛素高亲和力受体、低亲和力受体无明显差异;术后6 h口服组、静注组的血糖明显低于对照组,与处理前无显著差别;术后6 h各组血清胰岛素无显著差别,均显著高于处理前;胰岛素敏感指数、红细胞低亲和力受体三组均较处理前显著降低,但口服组、静注组明显高于对照组;术后6 h口服组、静注组红细胞高亲和力受体无明显降低;口服组与静注组间的血糖、胰岛素、胰岛素敏感指数及红细胞胰岛素受体无明显差别.结论术前静脉输注葡萄糖可缓解术后胰岛素抵抗的程度,术前饮用碳水化合物具有同样的效果,是一种简单有效的治疗方法.