Biochemical changes in the exocrine pancreas of rats fed caffeine

Coffee consumption has been associated with pancreatic disorders, but the mechanisms involved remain to be elucidated. This investigation examines the effects of caffeine consumption on the structure and function of the exocrine pancreas. Groups of rats, fed ad libitum commercial laboratory diet, were given drinking water which contained either caffeine (0.09 mg/ml) or nothing at all. The rats were allowed drink ad libitum and were killed 6 weeks later. Final body and pancreatic weights were not significantly different between the groups at the end of the experimental period. Although no ultrastructural effects of caffeine on the pancreas were observed, amylase and trypsinogen activity was 35% higher in pancreatic homogenates from caffeine-fed rats compared with controls. In addition, levels of immunoreactive cationic trypsin(ogen) were 41% higher than control levels in pancreases from the caffeine-fed rats. Also, the circulating levels of amylase and immunoreactive cationic trypsin(ogen) in serum were lower in the caffeine group compared with controls. When dispersed pancreatic acini isolated from the caffeine-fed rats were incubated in vitro with increasing concentrations of CCK-8 or nicotine, the rate of release of amylase, trypsinogen, and chymotrypsinogen was lower than in the control rats. This effect did not appear to be due to inhibition of protein synthesis, as determined by [3H]leucine incorporation into acinar protein. These data suggest that prolonged intake of caffeine at common dietary levels inhibits pancreatic enzyme secretion.     

Ultrastructural morphometry of matrical changes induced by exercise and food restriction in the rat calcaneal tendon.

The ultrastructural morphometry of collagen fibril populations in 24 calcaneal tendons obtained from 12 Fischer 344 rats were studied to elucidate matrical changes induced by food restriction and/or endurance exercise. Rats were randomly assigned to four equal groups: ad libitum control (AC), ad libitum exercise (AE), restricted diet control (RC) and restricted diet exercise (RE) groups. Beginning from 6 weeks of age, animals in the two food restriction groups were fed 60% of the mean food consumption of ad libitum fed rats. Then, starting from 6-7 months of age, the rats in the two exercise groups performed 40-50 min of treadmill running at 1.2-1.6 miles h-1 every day for a total of 10 weeks. Endurance training did not significantly alter body weight, but food restriction with or without exercise resulted in a significant loss of body weight. In ad libitum fed controls, food restriction alone did not significantly alter the mean collagen fibril CSA, but predisposed a preponderance of small-sized collagen fibrils. Endurance training per se induced a significant (32%) increase in mean fibril CSA (P less than 0.05), but this adaptive response to exercise was prevented by food restriction, as indicated by a 33% decline in fibril CSA (P less than 0.05). These findings demonstrate that dietary restriction modifies the adaptation of tendon collagen morphometry in response to endurance training, and that weight loss is better achieved with food restriction than endurance exercise.     

Effect of food restriction on cold adaptability of rats

To determine the role of the nutritional state in nonshivering thermogenesis during cold adaptation, cold adaptability was compared between cold-adapted (5 degrees C for 4-5 weeks) rats fed ad libitum and cold-adapted rats pair fed with warm controls having the same food intake. Cold-adapted pair-fed rats suffered a significant loss in body weight during cold exposure. However, brown adipose tissue (BAT) in both cold-adapted ad libitum fed and cold-adapted pair-fed rats was enlarged to the same extent as compared with that in control rats. Fat-free dry matter in BAT also increased in cold-adapted ad libitum fed and cold-adapted pair-fed rats to the same extent. Cold tolerance as assessed by the change in the colonic temperature at -5 degrees C was improved relative to control rats and was the same for cold-adapted ad libitum fed and cold-adapted pair-fed rats. Nonshivering thermogenesis as estimated by the noradrenaline-induced increase in oxygen consumption was significantly greater in the cold-exposed rats and there was no significant difference between cold-adapted ad libitum fed and cold-adapted pair-fed rats. These results suggest that an improved cold tolerance by means of nonshivering thermogenesis in brown adipose tissue is closely related to the low temperature itself but not the increased food intake which occurred in the cold.     

Ethane production rate in vivo is reduced with dietary restriction

Dietary restriction without malnutrition prolongs life and has a beneficial effect on age-related diseases and metabolic derangements. To test the effect of food restriction on ethane production rate, ethane exhalation was measured in rats with partial food restriction. Ethane production rate in room air in rats fed 60% of food consumed by ad libitum-fed animals for 2 wk was significantly reduced (3.50 +/- 0.25 vs. 5.21 +/- 0.34 pmol.min-1.100 g body wt-1, P less than 0.01). In 100% oxygen, ethane production in food-restricted rats was not different from that of ad libitum-fed rats (21.81 +/- 1.25 vs. 19.57 +/- 1.89 pmol.min-1.100 g-1). Fifteen hours of fasting compared with ad libitum feeding reduced ethane production modestly in room air (4.37 +/- 0.45 vs. 5.21 +/- 0.34 pmol.min-1.100 g-1) and more significantly in 100% oxygen (12.37 +/- 0.78 vs. 19.57 +/- 1.89 pmol.min-1.100 g-1). Thus, in 100% oxygen, 15 h of fasting, compared with ad libitum feeding, resulted in an approximately 40% decrease in ethane production rate. It is concluded that short-term food restriction significantly reduces ethane exhalation rate in rats when measured in room air.     

Effects of caecectomy in the young adult female rat on digestibility of food offered ad libitum and in restricted amounts.

Caecectomized and sham-operated rats were fed a laboratory chow ad libitum and the effects of caecectomy on the digestibility of the food were studied. Compared with sham-operated controls, caecectomized rats showed a decrease in apparent digestibiltiy of organic matter from 77.8 to 73.0%, of crude protein from 83.0 to 79.4%, and of 'carbohydrate' from 74.6 to 69.0%. However, faecal water content increased from 41.6 to 54.8%. 51Cr-labelled EDTA was excreted faster in the faeces after caecectomy. The colon partly adapted to the loss of caecal mucosa by increased length and thus mucosal surface area. In a second concurrent experiment the effect of caecectomy on the apparent digestibility of food during food restriction was studied. Six caecectomized rats, comparable in all respects to those used in the first study, were fed the laboratory chow ad libitum for 3 weeks. They were then fed submaintenance amounts of food to achieve body weight losses of 40--50% and to maintain these low weights for 4 weeks. Finally, they were again fed ad libitum for 3 weeks. During the period of restriction the apparent digestibility of organic matter increased from 72.7 to 75.4%. This was largely due to the increased apparent digestibility of crude protein which rose from 78.4 to 81.9%. Digestibility coefficients returned to control values immediately upon refeeding ad libitum.     

Protective effect of long term high fiber diet consumption on rat exocrine pancreatic function after chronic ethanol intake

The effects of ethanol administration on exocrine pancreas have been widely studied, but little is known about the effect of dietary fiber in combination with chronic ethanol on exocrine pancreatic function. The aim of this work was to examine the chronic effects of a high fiber diet, ethanol ingestion, and a combination of both on the function of the rat exocrine pancreas. Four groups of rats were fed for six months the following diets: 1.- NW: standard laboratory diet; 2.- FW: high fiber diet (15% cellulose); 3.- NE: standard laboratory diet and 20% ethanol in the drinking water; and 4.- FE: high fiber diet and 20% ethanol. Cholecystokinin (CCK) and acetylcholine (Ach) effects on amylase release and intracellular calcium mobilization in pancreatic acini were studied. In rats fed a 20% ethanol (NE), both the basal amylase release and the basal [Ca(2+)](i) were significantly increased; nonetheless, CCK and Ach-induced amylase release were significantly reduced compared with control rats. Ach- but not CCK-stimulated [Ca(2+)](i) increase in NE rats was significantly decreased compared with NW. In rats fed a combination of ethanol and a high fiber diet (FE) all the parameters under study were not significantly affected compared to control rats (NW). In conclusion, high fiber consumption does not alter the function of the exocrine pancreas. However, it ameliorates the deleterious effect of chronic ethanol consumption on pancreatic amylase secretion and, at least partially, reverses the ethanol-induced alterations on [Ca(2+)](i) in the rat exocrine pancreas.     

Effect of age and dietary restriction on protein synthesis by isolated kidney cells

The influence of age and food restriction on kidney protein synthesis was studied in Fischer F344 rats. The rate of total protein synthesis by suspensions of kidney cells declined 60% between 4 and 31 months of age. The rate of protein synthesis by kidney cells isolated from 19-month old rats fed a restricted diet (60% of diet consumed by rats fed ad libitum) was 45% higher than the rate of protein synthesis by kidney cells isolated from 19-month old rats fed ad libitum. The excretion of protein in the urine was measured to assess the effect of the age related decline in protein synthesis on kidney function. A dramatic increase in proteinuria was observed with increasing age, and rats fed the restricted diet excreted significantly less protein in the urine than rats fed ad libitum.     

Differential effect of long-term food restriction on fatty acid synthase and leptin gene expression in rat white adipose tissue.

Long-term food restriction (85%, 70% and 50% of ad libitum energy intake for one month) induced a substantial fall in serum leptin concentration and leptin mRNA levels in epididymal white adipose tissue in rats. Surprisingly, this suppression was not reversed by refeeding ad libitum for 48 h. The reduction in serum leptin concentration and leptin mRNA level did not strictly correlate with reduction in fat or body mass. Unlike serum leptin concentration and epididymal adipose tissue leptin mRNA levels, fatty acid synthase activity, fatty acid synthase protein abundance and fatty acid synthase mRNA levels increased significantly in white adipose tissue after refeeding rats subjected to food restriction. The increase in serum insulin concentration was observed in all groups on different degrees of food restriction and refed ad libitum for 48 h compared to controls. A decrease in serum insulin concentration was found in the rats not refed before sacrifice. Long-term food restriction did not significantly affect serum glucose concentrations in either refed or non-refed rats. The data reported in this paper indicate that there is no rapid rebound in serum leptin concentration or leptin gene expression in contrast to the increase in serum insulin concentration and fatty acid gene expression in white adipose tissue of rats refed ad libitum after one month's food restriction.     

Sibutramine alters the central mechanisms regulating the defended body weight in diet-induced obese rats

Chronic administration of sibutramine lowers body weight, presumably by altering brain monoamine metabolism. Here the effect of sibutramine on sympathoadrenal function (24-h urine norepinephrine and epinephrine levels) and arcuate nucleus (ARC) neuropeptide Y (NPY) and proopiomelanocortin (POMC) expression was assessed in diet-induced obese rats fed a low-fat diet. Chronic (10 wk) sibutramine [5 mg. kg(-1). day(-1) ip; rats fed ad libitum and injected with sibutramine (AS)] lowered body weight by 15% but only transiently (3-4 wk) reduced intake compared with vehicle-treated controls [rats fed chow ad libitum and injected with vehicle daily (AV)]. Other rats food restricted (RS) to 90% of the weight of AS rats and then given sibutramine restored their body weights to the level of AS rats when allowed libitum food intake. After reequilibration, RS rats were again energy restricted to reduce their weight to 90% of AS rats, and additional vehicle-treated rats (RV) were restricted to keep their body weights at the level of AS rats for 3 wk more. Terminally, total adipose depot weights and leptin levels paralleled body weights (AV > AS = RV > RS), although AS rats had heavier abdominal and lighter peripheral depots than RV rats of comparable body weights. Sibutramine treatment increased sympathetic activity, attenuated the increased ARC NPY, and decreased POMC mRNA levels induced by energy restriction in RV rats. Thus sibutramine lowered the defended body weight in association with compensatory changes in those central pathways involved in energy homeostasis.     

Effects of prior or concurrent food restriction on amylin-induced changes in body weight and body composition in high-fat-fed female rats

Amylin infusion reduces food intake and slows body weight gain in rodents. In obese male rats, amylin (but not pair feeding) caused a preferential reduction of fat mass with protein preservation despite equal body weight loss in amylin-treated (fed ad libitum) and pair-fed rats. In the present study, the effect of prior or concurrent food restriction on the ability of amylin to cause weight loss was evaluated. Retired female breeder rats were maintained on a high-fat diet (40% fat) for 9 wk. Prior to drug treatment, rats were either fed ad libitum or food restricted for 10 days to lose 5% of their starting body weight. They were then subdivided into treatment groups that received either vehicle or amylin (100 microgxkg(-1)xday(-1) via subcutaneous minipump) and placed under either a restricted or ad libitum feeding schedule (for a total of 8 treatment arms). Amylin 1) significantly reduced body weight compared with vehicle under all treatment conditions, except in always restricted animals, 2) significantly decreased percent body fat in all groups, and 3) preserved lean mass in all groups. These results indicate that amylin's anorexigenic and fat-specific weight loss properties can be extended to a variety of nutritive states in female rats.     

Circadian Rhythms of Rat Pancreatic Acinar Cells

On the basis of the circadian oscillations of the rat’s exocrine pancreatic function and previous reports on concomitant ultrastructural changes in the pancreatic tissue, we analysed stereologically the circadian rhythmicity in the structure of this organ. Twenty-four male Wistar rats, four and a half months old, were singly housed two months before the experiment in a lighting regimen LD=12:12, constant environmental temperature and relative humidity, with food and water ad libitum. The experiment was performed in winter. The rats were randomly divided into 6 balanced groups and killed under ether anesthesia at 6 equidistant time points in 24 hours. The pancreatic tissue was fixed in glutaraldehyde and osmium and embedded in Epon. 1 µm thick sections were examined by light microscopy for the evaluation by stereological methods of: a) volume fractions of the different parenchymal components of the exocrine pancreas; b) surface fractions of acinar cell faces; c) size distribution of acinar cell nuclei, their number per unit tissue volume and their mean diameter. Single cosinor method analysis of the data demonstrated statistically significant circadian rhythms for the volume fraction of the cytoplasm of acinar cells and the volume fractions of pancreatic acini and acinar cells. The volume fraction of the cytoplasm of the rat pancreatic acinar cells undergoes circadian oscillations with the highest values at the end of the light span; this rise precedes the well-known physiological nocturnal surge of pancreatic digestive enzymes. Our findings further support the hypothesis of a close relationship between pancreatic cell structure and its function.     

Circadian Rhythms of Rat Pancreatic Acinar Cells

On the basis of the circadian oscillations of the rat's exocrine pancreatic function and previous reports on concomitant ultrastructural changes in the pancreatic tissue, we analysed stereologically the circadian rhythmicity in the structure of this organ. Twenty-four male Wistar rats, four and a half months old, were singly housed two months before the experiment in a lighting regimen LD=12:12, constant environmental temperature and relative humidity, with food and water ad libitum. The experiment was performed in winter. The rats were randomly divided into 6 balanced groups and killed under ether anesthesia at 6 equidistant time points in 24 hours. The pancreatic tissue was fixed in glutaraldehyde and osmium and embedded in Epon. 1 µm thick sections were examined by light microscopy for the evaluation by stereological methods of: a) volume fractions of the different parenchymal components of the exocrine pancreas; b) surface fractions of acinar cell faces; c) size distribution of acinar cell nuclei, their number per unit tissue volume and their mean diameter. Single cosinor method analysis of the data demonstrated statistically significant circadian rhythms for the volume fraction of the cytoplasm of acinar cells and the volume fractions of pancreatic acini and acinar cells. The volume fraction of the cytoplasm of the rat pancreatic acinar cells undergoes circadian oscillations with the highest values at the end of the light span; this rise precedes the well-known physiological nocturnal surge of pancreatic digestive enzymes. Our findings further support the hypothesis of a close relationship between pancreatic cell structure and its function.     

Malnutrition sequela on the drug metabolizing enzymes in male Holtzman rats

The effect of food restriction on the specific activities of the drug metabolizing enzymes (DME) system was studied in Holtzman male rats by comparing DME activities in 90-day-old control rats fed ad libitum (CO), rats fed 40% restricted food (RF) from the gestation period to the day of sacrifice, and recovered rats (rRF) fed 40% restricted food from period of gestation to 45 days of age and then fed ad libitum until the day of sacrifice. In liver, total cytochrome P450 (CYP) of the RF and rRF groups was higher by approximately 50% and 28%, respectively, than in CO rats. Specific activities of individual CYP monooxygenases (MO) such as CYP2B [7-methoxycoumarin demethylase (MOCD)], CYP1A [aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin deethylase (EORD)], and CYP2E [nitrosodimethylamine demethylase (NDMAd)] were 31, 61, 43, and 56% in RF and 16, 36, 26, and 32% in rRF groups, respectively, more than the CO values. Conjugases such as UDP- glucuronosyltransferases with substrates 3-OH benzo(a)pyrene (UGT1) and 4-hydroxybiphenyl (UGT2) and glutathione S-transferase (GST) with substrate 1-chloro-2,4-dinitrobenzene were higher by 72, 69, and 33% in RF and 28, 38, and 24% in rRF groups, respectively. MO activities (MOCD and EORD) were significantly higher in lung, kidney, and intestine: MOCD by 82, 48, and 45% in RF and 40, 25, and 22% in rRF, respectively; and EORD by 84, 77, and 67% in RF and 40, 33, and 28% in rRF, respectively. However, activity of conjugases (UGT1 and GST) were significantly lower (approximately 35-45%) in RF and rRF rats (approximately 20-30%) than in the CO group in above mentioned extrahepatic tissues. These studies indicate that undernourishment during the period of gestation, weanling, and growth and development of microsomal enzymes produces a sequela of events on the DME in hepatic and extrahepatic tissues that cannot return to the control values even when fed ad libitum.     

Circadian influences on feeding-induced changes in ACTH and corticosterone secretion in rats.

Food ingestion has a variable influence on pituitary-adrenal hormone secretion depending on the species studied and/or the experimental design. In this study, changes in plasma concentrations of ACTH and corticosterone following 30 min of food ingestion were compared in both 24 h fasted and ad libitum fed rats tested during either the early light cycle or the early dark cycle. In the dark, food ingestion caused significant decreases in both ACTH (to 80% of control) and corticosterone (to 32% of control) in both fasted and ad libitum fed rats. In contrast, in the light, food ingestion by the fasted animal resulted in a doubling of corticosterone concentrations. Such a response was not seen in ad libitum fed animals; however, these animals ate very little during the test. There were no significant changes in ACTH during the light phase. These data indicate that time of day has a significant impact on the responses of the pituitary-adrenal system to food ingestion. This circadian effect may be due to the influence of the endogenous levels of ACTH/corticosterone existing at the time of food ingestion.     

Effect of fasting and refeeding on duodenal alkaline phosphatase activity in monosodium glutamate obese rats

In the present work the effects of fasting and refeeding on fat pad weight and alkaline phosphatase activity in the brush border of individual duodenal enterocytes have been evaluated in male Wistar rats with obesity induced by monosodium glutamate (MSG) treatment during the early postnatal period. Neonatal rats were treated subcutaneously with MSG (2 mg/g b.w.) or saline (controls) for 4 days after birth. At 4 months of age, two types of experiments were performed. In the first experiment rats, were submitted to 3 or 6 days lasting food deprivation. In the second experiment the rats were refed for 3 or 6 days ad libitum or restrictedly (60% of pre-fasting intake) after a 6 day-fasting period. Fasting and refeeding influenced the body fat and function of the duodenum in MSG-treated rats differently as compared to the controls. However, alkaline phosphatase activity and the weight of epididymal and retroperitoneal fat depots were significantly increased in MSG obese rats (P<0.001) during all the periods examined. While 3 days of food deprivation resulted in both groups in a similar loss of adipose tissue weight and alkaline phosphatase activity, the decrements of these parameters after 6 days of fasting were lower in obese rats suggesting that their capacity to spare body fat stores was enhanced. After 3 days of ad libitum refeeding, a more marked adaptational increase of food consumption and also a significantly increased alkaline phosphatase activity above the pre-fasting level (P<0.01) was observed in the MSG-treated rats. Consequently, a more rapid body fat restoration was demonstrated in these animals. Refeeding of rats at 60% of the pre-fasting intake level resulted in a significant increase of alkaline phosphatase activity in both the MSG and control group; moreover, as food restriction continued, MSG-treated rats tended to further increase the enzyme activity. Our results revealed that MSG treatment of neonatal rats may significantly change the intestinal functions. Permanently increased alkaline phosphatase activity observed in MSG obese rats during all investigated periods suggests that this functional alteration is probably not a consequence of actual nutritional variation but could be a component of regulatory mechanisms maintaining their obesity at critical values.     

Folate deficiency and pancreatic acinar cell function

The present study was designed to determine the effect of folate deficiency on pancreatic acinar cell function. In the first series of experiments, three groups of rats were fed ad libitum regular rat feed, folate-deficient diet, or an equivalent amount of folate-sufficient diet. In the second series of experiments, rats were either fed ad libitum or rendered folate deficient by a purified folate-deficient diet; half of the folate-deficient group was replenished with oral folate. Body weight, pancreatic weight, DNA [methyl-14C]thymidine incorporation into DNA, RNA, [8-14C]adenine incorporation into RNA, protein content, synthesis of proteins, amylase content, and basal and bethanechol-stimulated amylase secretion were determined. The parameters were the same in the rats fed a folate-sufficient diet as in those fed a regular rat feed. Feeding a folate-deficient diet resulted in impaired DNA synthesis as evidenced by diminished incorporation of [methyl-14C]thymidine into DNA. There was no change in secretion of amylase. Similar results were obtained in the second series of experiments. These studies indicate that folate deficiency (rather than antibiotic content of the diet) impaired pancreatic function. Folate deficiency may therefore contribute to pancreatic injury in malnutrition and alcoholism.     

Activity of pancreatic antioxidative enzymes and malondialdehyde concentrations in rats with hyperglycemia caused by fluoride intoxication.

The aim of this work was to examine the effect of fluoride ions on antioxidative enzyme activity in the pancreas of rats exposed during 4 months to NaF in drinking water. The study was carried out in 30 four-week-old male Wistar FL rats, that were randomly assigned to three equal groups and given distilled water ad libitum for three weeks. Subsequently, two examined groups of animals were exposed to NaF in drinking water: group 1 (10 rats) at 50 mg F(-)/L (2.63 mmol/L), group 2 (10 rats) at 100 mg F(-)/L (5.26 mmol/L). The control group (10 rats) received distilled water. After 4 months the animals were anesthetized with ether prior to collection of pancreas and cardiac blood. Serum concentrations of glucose and fluoride, as well as activities of the cytoplasmic (CuZn-SOD) and the mitochondrial (Mn-SOD) superoxide dismutase, glutathione peroxidase (GSH-Px) and concentrations of malondialdehyde (MDA) in the homogenized pancreas were measured. The activity of CuZn-SOD was reduced by 50% and a tendency to lower activities of Mn-SOD was observed. No changes were noted in the activity of GSH-Px or concentrations of MDA. We conclude that: 1) the fluoride caused hyperglycemia in rats in this study is not accompanied by an activation of the free radical production in the pancreas; 2) the hyperglycemia in the exposed rats cannot be attributed to pancreatic damage caused by fluoride ions (the cause in this case appears to be extrapancreatic); 3) the inhibition of pancreatic CuZn-SOD is probably due to the direct action of fluoride on the enzyme.     

Age-correlation of protein utilization to saccharide intake

Male Wistar rats aged 30, 90, 150 and 360 days were fed ad libitum on diets with an optimum protein and fat content for their respective ages and an increasing saccharide content. Net protein utilization (NPU) was determined from the body nitrogen and protein intake values and the course of gluconeogenesis in the liver was measured by specific phosphoenolpyruvate carboxykinase (PEPCK) activity. According to the growth curve for the standard diet, animals aged 30 and 90 days have a high growth rate (3.245 g/day), 150-day-old rats grow more slowly (1.856 g/day) and 360-day-old animals put on scarcely any weight at all (277 mg/day). In 30-day-old rats, NPU attains maximum values in the presence of a 36% saccharide content in the diet, in 3- and 5-month-old animals in the presence of 51% saccharides and in one-year-old animals in the presence of 41% saccharides in their food. The course of gluconeogenesis also corresponds to these values. PEPCK activity in the youngest age group is greatest in the presence of 31% saccharides in the food, at 90 days it is stimulated in the presence of 31-46% saccharides, at 150 days the decisive concentration is 41 and 46% and at one year proteins are used for saccharide synthesis in diet with a 31 and 36% saccharide concentration. For optimum saccharide values, PEPCK activity is reduced in every age group; together with the maximum NPU values, this indicates that proteins are used for growth and building of the organism at an early age and for the renewal of tissues and organs and maintenance of the organism in adulthood.     

Increments in glucose, glucagon and insulin after morphine in rats, and naloxone blocking of this effect.

In awake rats adapted to experimental conditions and allowed food ad libitum, hyperglycemia was induced by the administration of morphine 10 mg/kg through indwelling catheters in the external jugular vein. High glucose values were measured at 5, 15 and 25 min. Glucagon values were high at 5 and 15 min, and again at basal level at 25 min. Insulin was increased after morphine both at 5, 15 and 25 min, whereas somatostatin levels did not change after morphine. When morphine was administered together with naloxone after an initial 10 min period of naloxone administration, there was no increment in glucose, insulin or somatostatin values; neither at 5, 15 or 25 min. There was a remarkable glucagon decrease after naloxone and morphine remaining from 5 to 25 min. Then, one of the possible mechanisms for the hyperglycemic response after morphine may be an opioid effect on pancreas, stimulating glucagon and thereby causing hepatic glucose output.     

Motivation to obtain preferred foods is enhanced by ghrelin in the ventral tegmental area

Ghrelin is an orexigenic peptide that acts within the central nervous system to stimulate appetite and food intake via the growth hormone secretagogue receptor (GHS-R). It has been hypothesized that ghrelin modulates food intake in part by stimulating reward pathways in the brain and potentially stimulating the intake of palatable foods. Here we examined the effects of chronic ghrelin administration in the ventral tegmental area (VTA) via osmotic minipumps on 1) ad libitum food intake and bodyweight; 2) macronutrient preference; and 3) motivation to obtain chocolate pellets. In the first study rats receiving ghrelin into the VTA showed a dose-dependent increase in the intake of regular chow, also resulting in increased body weight gain. A second study revealed that intra-VTA delivery of the ghrelin receptor antagonist [Lys-3]-GHRP-6 selectively reduced caloric intake of high-fat chow and reduced body weight gain relative to control and ghrelin treated rats. The third study demonstrated that food restricted rats worked harder for food pellets when infused with ghrelin than when infused with vehicle or ghrelin receptor antagonist treated rats. Finally, rats trained on an FR1 schedule but returned to ad libitum during ghrelin infusion, responded at 86% of baseline levels when they were not hungry, whereas saline infused rats responded at 36% of baseline. Together, these results suggest that ghrelin acts directly on the VTA to increase preference for and motivation to obtain highly-palatable food.