The effects of dietary flaxseed on the Fischer 344 rat: I. Development, behaviour, toxicity and the activity of liver gamma-glutamyltranspeptidase

The effect of exposure to, followed by consumption of, 10% flax chow from the 18th day of gestation to the 86th day after birth was examined in male and female Fischer 344 rats. Growth curves of the flax chow-fed rats were identical to those of regular chow-fed rats, as were such developmental milestones as pinna development, growth of hair and eye opening. Acoustical startle and the righting reflexes, developmental behavioural indices, were also the same. Blood glucose levels were comparable in flax chow-fed and regular chow-fed rats at all stages of development, indicating that flax is without effect on glucose balance. There were no signs of toxicity in the flax chow-fed rats since their plasma levels of alanine aminotransferase and gamma-glutamyltranspeptidase (gammaGT) were the same as those of regular chow-fed rats. The activity of gammaGT displayed an increase in the livers of flax chow-fed rats after puberty, more so in the male-four-fold-than in the female-1.38-fold. This is suggestive of an estrogenic effect which implicates an effect of an estrogenic flax lignan. An hepatobeneficial effect of the flax-induced increase in liver gammaGT is discussed. In summary, dietary 10% flax chow is without long-term effect on growth, development and behaviour, is non-toxic and may be hepatoprotective.     

Sucrose feeding effects inhibition of gamma-glutamyltranspeptidase in the liver of the rat: possible mediation by thyroid hormone

The effect of sucrose on Fischer 344 rat liver gamma-glutamyltranspeptidase (gammaGT) was studied: in adults fed sucrose for 3 weeks; and rats exposed to sucrose from the 18th day of gestation to the 40th day after birth. Rats fed regular rodent chow served as controls. Sucrose caused mild lipemia; and in the liver an increase in size and fat build-up without damage. In adult sucrose-fed rats, compared to controls, plasma glucose levels were increased: 1.12-, 1.40- and 1.13-fold after 24, 48h and 3 week consumption of sucrose, respectively. Insulin levels were unaltered for the first week of sucrose consumption but increased from control levels: 16% at 1 week, and 2.0-fold at 3 weeks. The T3 levels were comparable to control levels 24h after the sucrose was started and were increased: 1.22-, 1.13- and 1.12-fold at 48h, 1 and 3 weeks, respectively. The T4 levels were comparable at all time points between sucrose-fed and control rats. Liver gammaGT activity exhibited a steady decrease from control levels: after 24, 48h, 1 and 3 weeks of sucrose feeding the decrease was 5, 8, 21 and 37%, respectively in homogenates; and 10, 17, 24 and 41%, respectively in plasma membranes. Perinatal sucrose exposure effected in 40-day-old rats, compared controls: a 1.09-fold increase in plasma glucose; no change in plasma insulin; an increase of 1.15- and 1.39-fold in plasma levels of total and free T3, respectively; a decrease of 20 and 14% in plasma levels of total and free T4, respectively. gammaGT activity was decreased in liver plasma membranes isolated from sucrose-exposed rats relative to those of control: 80% in the male; 82% in the female. Relative specific activities of gammaGT were the same in both males: 15.4 and 16.1 in control and sucrose-exposed male rats, respectively; and females: 14.1 and 15.4 in control and sucrose-exposed female rats, respectively. gammaGT was 2-fold higher in the livers of female relative to male rats in sucrose-exposed and control groups. Kidney gammaGT activities were the same in control and sucrose-exposed rats. The involvement of T3 in the sucrose-induced decrease in liver gammaGT is discussed.     

The effects of dietary flaxseed on the Fischer 344 rat. III. Protection against CCl(4)-induced liver injury

The hepatotoxic effect of carbon tetrachloride (CCl(4)) administered by gavage at 0.25 ml CCl(4) (1:1 in olive oil) per 100 g body weight was examined 24 h later in regular chow fed (RC) and 10% flax chow fed (FC) male and female Fischer 344 rats. CCl(4)-treated RC rats were subdued, lethargic and unkempt. CCl(4)-treated FC rats were much less affected. CCl(4) treatment resulted in loss of weight in RC and FC rats. In males, the weight loss was 6.7% body mass in RC rats compared to 5.6% body mass in FC rats. In females, the weight loss was 7.5% body mass in both RC and FC rats. While CCl(4) treatment increased the level of the liver injury marker plasma alanine aminotransferase (ALT) in RC rats, this CCl(4) effect was significantly attenuated in FC rats. In male rats, the ALT increase was 435-fold in RC rats and 119-fold in FC rats, over that of their respective controls. In female rats, the ALT increase was 454-fold in RC rats and 381-fold in FC rats, over that of their respective controls. These results provide evidence that flax consumption protects the liver against injury and that the extent of the protection is sex dependent. CCl(4) had no effect on the plasma level of gamma-glutamyltranspeptidase (gammaGT) in RC and FC rats supporting the contention that plasma gammaGT is not a useful marker for acute liver injury which is seen in this model. The activity of gammaGT was increased in the livers of FC rats compared to RC rats: 2.7-fold in males and 1.5-fold in females. In RC rats, the activity of liver gammaGT was decreased by CCl(4) treatment: 70% in the male and 25% in the female. However, this CCl(4) effect was reversed or abolished by flax consumption. Compared to RC rats: in male FC rats, CCl(4) actually increased the activity of liver gammaGT 1.28-fold; while in female FC rats, the depressing effect of CCl(4) treatment was abolished. The flax-induced preservation of gammaGT in the liver in response to injury may be involved in the observed hepatoprotection through generation of GSH. In RC male rats, CCl(4) treatment effected a 25% reduction in plasma glucose levels. There was no decrease in CCl(4)-treated FC male rats. In female rats, CCl(4) treatment effected a 21% decrease in plasma glucose levels in both RC and FC rats. In conclusion, multiple parameters for acute CCl(4)-induced injury were attenuated in the FC compared to the RC rat. That flaxseed consumption conferred greater protection against liver injury in the male than in the female suggests an involvement of the estrogenic lignan component of flaxseed. We discuss the possibility that this hepatoprotection is through a flax lignan-induced increase in reduced glutathione related to a flax effect on the activity of liver gammaGT in the resting state and the maintenance of its activity in response to injury.     

The effects of dietary flaxseed on the Fischer 344 rat: II. Liver gamma-glutamyltranspeptidase activity

The effect of 10% flax chow consumption from the 30th to the 130th day after birth was examined in male Fischer 344 rats. The effects of both the high lignan/high oil Norlin strain and a high lignan/low oil Solin strain of flaxseed were compared. Physically and behaviourally there were no differences in rats belonging to the three dietary groups at any time. At 50 and 100 days of dietary exposure, blood glucose levels were the same in Norlin and Solin flax chow-fed and as well as regular chow-fed rats; there were no signs of toxicity in the Norlin and Solin flax-fed rats since their plasma levels of alanine aminotransferase were the same and equal to those of regular chow-fed rats. The activity of gamma-glutamyltranspeptidase (gammaGT) displayed an increase in the liver homogenates of flax chow-fed rats. This increase was the same in Norlin and Solin flax-fed rats at 50 and 100 days. Thus the liver effect was not oil, but lignan, likely secoisolariciresinol diglucoside (SDG), induced and was effected early on, and sustained, after flax exposure. The degree of heat activation of liver homogenate gammaGT was the same in regular chow-fed and flax chow-fed rats. Compared to liver homogenate gammaGT activity, the soluble form of gammaGT was expressed at very low levels while the plasma membrane-bound form of gammaGT was expressed at very high levels in rat liver in both regular chow-fed and flax chow-fed rats. There was no effect of flax feeding on the soluble form of liver gammaGT which was expressed at a very low level. Flax feeding effected an increase in the activity of gammaGT in isolated plasma membrane fractions which mirrored that in liver homogenates: the same degree of increase was seen in Norlin flax chow-fed and Solin flax chow-fed rats. Flax consumption effects an increase in the activity of liver gammaGT at the level of the plasma membrane which is lignan dependent, physiologically relevant and may be linked to hepatoprotection against injury through an increase in reduced glutathione.     

Different responses of circulating ghrelin, obestatin levels to fasting, re-feeding and different food compositions, and their local expressions in rats

Obestatin, a sibling of ghrelin derived from preproghrelin, opposes several physiological actions of ghrelin. Our previous study has demonstrated that both plasma ghrelin and obestatin levels were decreased significantly 2h after food intake in human. To further expand current knowledge, we investigated the temporal profiles of their levels in ad libitum fed rats, 48h fasted rats and 48h fasted rats refed 2h with a standard chow, crude fiber, 50% glucose or water, and their expressions in stomach, liver and pancreatic islets immunohistochemically. Plasma ghrelin and obestatin levels were measured by EIA. Plasma leptin, insulin and glucose levels were also evaluated. Both plasma ghrelin and obestatin levels increased significantly in fasted rats compared with ad libitum fed rats. The ingestion of standard chow produced a profound and sustained suppression of ghrelin levels, whereas plasma obestatin levels decreased significantly but recovered quickly. Intake of crude fiber or 50% glucose, however, produced a more profound and sustained suppression of obestatin levels, though they had relatively less impact on ghrelin levels. Plasma glucose was the only independent predictor of ghrelin levels, obestatin levels, and ghrelin to obestatin ratios. Obestatin immunoreactivity was detected in the fundus of stomach, liver and pancreatic islets, with roughly similar patterns of distribution to ghrelin. These data show quantitative and qualitative differences in circulating ghrelin and obestatin responses to the short-term feeding status and nutrient composition, and may support a role for obestatin in regulating metabolism and energy homeostasis.     

Effects Of A Post-Weaning Cafeteria Diet In Young Rats: Metabolic Syndrome,Reduced Activity And Low Anxiety-Like Behaviour

Among adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight.     

Effects of fructose and glucose on plasma leptin, insulin, and insulin resistance in lean and VMH-lesioned obese rats

To determine the influence of dietary fructose and glucose on circulating leptin levels in lean and obese rats, plasma leptin concentrations were measured in ventromedial hypothalamic (VMH)-lesioned obese and sham-operated lean rats fed either normal chow or fructose- or glucose-enriched diets (60% by calories) for 2 wk. Insulin resistance was evaluated by the steady-state plasma glucose method and intravenous glucose tolerance test. In lean rats, glucose-enriched diet significantly increased plasma leptin with enlarged parametrial fat pad, whereas neither leptin nor fat-pad weight was altered by fructose. Two weeks after the lesions, the rats fed normal chow had marked greater body weight gain, enlarged fat pads, and higher insulin and leptin compared with sham-operated rats. Despite a marked adiposity and hyperinsulinemia, insulin resistance was not increased in VMH-lesioned rats. Fructose brought about substantial insulin resistance and hyperinsulinemia in both lean and obese rats, whereas glucose led to rather enhanced insulin sensitivity. Leptin, body weight, and fat pad were not significantly altered by either fructose or glucose in the obese rats. These results suggest that dietary glucose stimulates leptin production by increasing adipose tissue or stimulating glucose metabolism in lean rats. Hyperleptinemia in VMH-lesioned rats is associated with both increased adiposity and hyperinsulinemia but not with insulin resistance. Dietary fructose does not alter leptin levels, although this sugar brings about hyperinsulinemia and insulin resistance, suggesting that hyperinsulinemia compensated for insulin resistance does not stimulate leptin production.     

Diazoxide prevents the development of hormonal and metabolic abnormalities present in rats fed a sucrose rich diet

We have previously reported that normal Wistar rats fed an isocaloric, sucrose-rich (63%) diet (SRD) developed glucose intolerance and elevated triglyceride levels in plasma (P) as well as in heart (H) and liver (L) tissue. This metabolic state was accompanied by hyperinsulinism both in vivo and in vitro, suggesting that a state of insulin resistance has developed. In order to gather information on the role of hyperinsulinemia and glucose intolerance in the development of the above lipid metabolism abnormalities, diazoxide, a known insulin release blocking agent was administered (120 mg/kg/day) together with the diet (SRD + DZX) for 22 days. Control groups fed a standard chow (STD) or the STD plus diazoxide (STD + DZX) were included in the study. Under the present experimental design, DZX was able to prevent the development of hyperinsulinism, glucose intolerance and elevated levels of triacylglycerol in plasma, heart and liver present in animals fed on a sucrose rich diet. Our results suggest that mechanisms involved in the development of this nutritionally induced syndrome may include an interaction of hyperinsulinemia, with a direct effect of sucrose on several steps of lipid metabolism.     

Appearance and metabolic development of diabetes mellitus in the sand rat, Psammomys obesus

The aim of this study was to examine the long-term effects of synthetic chow diet on the metabolic pattern of diabetic syndrome in a large group of sand rats. Few animals had a fulminating reaction with markedly decreased glucose tolerance, low plasma insulin levels and death within 3-4 weeks. But the most of sand rats developed obesity and elevated plasma insulin levels. From the third month, 40% of sand rats presented a diabetic syndrome with hyperinsulinemia, hyperglycemia, markedly decreased glucose tolerance and insulin resistance. Plasma lipids were increased; the lipid and glycogen accumulation in the liver was high. So this diabetic syndrome can be compared to maturity onset diabetes. If this synthetic chow diet lasted more than 6 months, the most of animals lost considerable weight with a strong lipid depletion of fat stores. Serum immunoreactive insulin levels fall and the blood glucose rose over 500 mg/100 ml with glycosuria and ketonuria . The elevated triglyceride content of plasma and the lipid deposits in the liver were exaggerated; glycogen had disappeared. Animals developed an overtly insulin- dependent diabetes, the latter phase of the disease. The sand rat appears to us as a potentially interesting model for investigation both maturity onset and ketotic-type diabetic syndrome.     

Hepatic uptake of chylomicrons and triglyceride emulsions in rats fed diets of differing fat content

The hepatic removal of plasma chylomicrons was determined for rats fed the following diets: a) containing no triglyceride, b) regular chow diet with 4.5% of its mass as lipid and, c) a corn oil-supplemented chow with triglyceride accounting for 20% of the mass. The fractional hepatic uptake of either radiolabeled chylomicrons or a triglyceride emulsion was reciprocally related to the amount of lipid in the diet. The animals receiving only carbohydrate and protein calories had the most active hepatic uptake of particulate triglyceride and were observed to have a significant decrease in the plasma concentration of the C apolipoproteins. The addition of either C-I, C-II, or C-III apoproteins to the triglyceride emulsion prior to intravenous injection produced a significantly lower hepatic triglyceride recovery of emulsions containing apoC-III. When the plasma of animals fed a fat-free diet was supplemented with human C-III-1 apolipoprotein, the distribution into the liver of either enterally administered fatty acid or parenteral triglyceride was diminished. The triglyceride content in the liver of the rats fed fat-free or corn oil-supplemented diets was significantly greater than that of the control rats and composition was somewhat similar to that of lymph triglyceride. The studies indicate an important influence of dietary lipid on both the partition of plasma triglyceride into the liver and the steady state hepatic triglyceride content.     

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.     

High-energy diets produce different effects on fatty acid synthesis in brown adipose tissue, white adipose tissue and liver in the rat

The influence of feeding rats a high-energy diet for 7 days on fatty acid synthesis in brown adipose tissue, white adipose tissue and liver of the rat was investigated. The incorporation of 3H2O and [U-14C]glucose into fatty acid was measured in vivo. The rats fed the high-energy diets had higher rates of fatty acid synthesis in white adipose tissue than the controls fed on chow, while fatty acid synthesis in brown adipose tissue and liver was either decreased or unchanged relative to that of controls fed on chow. After an oral load of [U-14C]glucose the incorporation of radioactivity into tissue fatty acid was several-fold higher in brown adipose tissue than in white adipose tissue in rats fed on chow. In rats fed the high-energy diets, incorporation of radioactivity into fatty acid in brown adipose tissue was decreased while that into white adipose tissue was either increased (Wistar rats) or unchanged (Lister rats).     

A high cholesterol diet ameliorates renal tubular lesions in diabetic rats

These studies examine the effect of cholesterol feeding in normal rats and in rats with streptozotocin-induced diabetes mellitus. Four groups were studied: normal rats fed either a standard rat chow or a standard rat chow supplemented with cholesterol and diabetic rats fed standard chow or standard chow plus cholesterol. Diabetic rats fed a standard diet excreted more creatinine and urea in the urine, had higher levels of blood urea nitrogen, and lower serum albumin levels than rats fed standard diet plus cholesterol. Blood glucose levels were similar in the two groups; however, diabetic rats given cholesterol had a greater body weight at the end of the study than diabetic rats eating standard chow. Urine volumes and sodium and potassium excretion in the urine were greater in diabetic rats fed a standard diet than in those fed a high cholesterol diet. Diabetic rats fed a standard diet had distinctive renal lesions characterized by swelling of tubular epithelial cells with clearing of cytoplasm. The nephron segments involved by this striking vacuolar change were the distal convoluted tubule and the thick limbs of Henle's loop. These lesions were identical to those described by Armanni-Ebstein in severely glycosuric patients. These lesions were not observed in any of the animals of the other three groups (including diabetic rats fed a high cholesterol diet). Glomeruli were normal in animals of all groups. Thus, cholesterol administration prevents the development of the Armanni-Ebstein lesions in diabetic rats despite persistent hyperglycemia. The mechanism by which cholesterol administration prevents the accumulation of glycogen in distal tubule cells has not been elucidated. It is suggested that glycogen accumulation in distal tubular segments may explain the greater urine volumes, natriuresis, kaliuresis, and proteinuria observed in diabetic animals fed a standard diet when compared with rats fed the same diet plus cholesterol.     

Whole body insulin resistance in rat offspring of mothers consuming alcohol during pregnancy or lactation: comparing prenatal and postnatal exposure.

This study examined the effects of maternal ethanol (EtOH) consumption during pregnancy or lactation on glucose homeostasis in the adult rat offspring. Glucose disposal was determined by minimal model during an intravenous glucose tolerance test in rats that had a small or normal birth weight after EtOH exposure in utero and in rats whose mothers were given EtOH during lactation only. All three EtOH groups had decreased glucose tolerance index and insulin sensitivity index, but their glucose effectiveness was not different from that of controls. In addition, EtOH rat offspring that were small at birth had elevated plasma, liver, and muscle triglyceride levels. The data show that EtOH exposure during pregnancy programs the body to insulin resistance later in life, regardless of birth weight, but that this effect also results in dyslipidemia in growth-restricted rats. In addition, insulin resistance is also evident after EtOH exposure during lactation.     

Uptake of radiolabeled copper from portal blood containing fructose or glucose

The present investigation was designed to study the uptake of⁶⁷Cu when administered directly, into the portal vein, along with either functose or glucose, by the liver and extrahepatic tissues. Following weaning, male Sprague-Dawley rats were fed for 3 wk either commercial laboratory ration (chow) or semipurified diets deficient in Cu (0.6 ppm) or supplemented with Cu (6.0 ppm) and containing 62% carbohydrate as either fructuse or cornstarch. After an overnight fast, a single dose of rat plasma (0.1 mL) containing fructose or glucose extrinsically labeled with⁶⁷Cu was injected directly into their portal vein. Although not always statistically significant, rats fed chow retained more radioactivity in the liver and several extrahepatic tissues when⁶⁷Cu was administered with fructose than with glucose. Regardless of Cu status, rats fed diets containing fructose retained more radioactivity in extrahepatic tissues than rats fed starch. There was an increased uptake of⁶⁷Cu by the liver, blood, muscle, and fat pad when fructose as compared to glucose was injected in combination with the isotope. These data strongly suggest that Cu requirements or utilization are greater when fructose is the main dietary carbohydrate. The results may also in part explain the reason for the increased severity of Cu deficiency in rats fed fructose.     

Beneficial effects of combined treatment with niacin and chromium on the liver of hyperlipemic rats

Many studies have shown that niacin and Cr exert combined effects. Significant beneficial effects in serum lipid levels following Cr supplementation have been reported. Niacin decreases total plasma levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol and increases high-density lipoprotein cholesterol. In this study, 12-mo-old female Swiss albino rats were used. They were randomly divided into four groups. The animals of group I (control) were fed with pellet chow. Group II was fed with pellet chow and treated with 250 μg/kg CrCl₃·6H₂O and 100 mg/kg niacin for 45 d, by the gavage technique. The rats of group III were fed with lipogenic diet consisting of 2% cholesterol 0.5% cholic acid, and 20% sunflower oil added to the pellet chow and given 3% alcoholic water for 60 d. Group IV was fed with the same lipogenic diet, and 15 d after, the experimental animals were made hyperlipemic; they were treated with 250 μg/kg CrCl₃·6H₂O and 100 mg/kg niacin by gavage technique for 45d. On d 60, liver and blood samples were taken from the animals. The sections were examined under light and electron microscopes. Serum total lipid and cholesterol levels were determined by spectrophotometric methods. The aim of the present study was *** DIRECT SUPPORT *** A02Q2015 00004     

Effects of hypophysectomy and acute growth hormone treatment upon glucose metabolism in adipose tissues and isolated adipocytes of rats.

Glucose oxidation and incorporation into lipid were measured in epididymal adipose tissues and isolated adipose cells of normal and hypophysectomized rats in an effort to determine whether the acute hypoglycemic effect of a systemic growth hormone (GH) injection was related to alterations in the glucose metabolism of adipose tissue. The rats were fed rat chow or a high sucrose diet and received 100 mug GH intraperitoneally 30 minutes or three and one-half hours before sacrifice. Hypophysectomized rats showed a lower plasma glucose as compared with normal rats on both diets. Thirty minutes after a GH injection there was a further decrease of the plasma glucose which, however, was not present in those rats receiving GH three and one-half hours before sacrifice. Adipose tissues from hypophysectomized rats fed the high sucrose diet showed a blunted insulin sensitivity as compared with normal rats on a similar diet. The insulin sensitivity of these tissues was further decreased 30 minutes after a GH injection. Basal glucose metabolism of isolated adipocytes from hypophysectomized rats, as compared with normal rats, was depressed if they were fed rat chow, was at normal levels if they were fed the high sucrose diet and was increased if they were fed the sucrose diet and received triiodothyronine and cortisone supplements. No manipulations of diet or hormonal treatments made the isolated adipocyte from hypophysectomized rats sensitive to insulin either 30 minutes or three and one-half hours after a GH injection. Since basal glucose utilization is not enhanced by GH injection and both the blunted insulin sensitivity of adipose tissue and the absent insulin sensitivity of adipopocytes would be expected to produce hyperglycemia rather than hypoglycemia, it is concluded that immediate systemic effects of a GH injection on carbohydrate metabolism are not related to changes in glucose metabolism of the peripheral adipose tissues.     

Effect of maternal exercise on fetal liver glycogen late in gestation in the rat

To determine the effect of maternal exercise on fetal liver glycogen content, fed and fasted rats that were pregnant for 20.5 or 21.5 days were run on a rodent treadmill for 60 min at 12 m/min with a 0% grade or 16 m/min up a 10% grade. The rats were anesthetized by intravenous injection of pentobarbital sodium, and fetal and maternal liver and plasma samples were collected and frozen. Fetal liver glycogenolysis did not occur as a result of maternal exercise. Fetal blood levels of lactate increased 22-60%, but glucose, plasma glucagon, and insulin were unchanged during maternal exercise. Maternal liver glycogen decreased as a result of exercise in all groups of rats except the fasted 20.5-day-pregnant group. Plasma free fatty acids increased in all groups and blood lactate increased in fed (20.5 days) and fasted (21.5 days) pregnant rats. Maternal glucose, glucagon, and insulin values remained constant during exercise. The fetus appears to be well-protected from metabolic stress during moderate-intensity maternal exercise.     

Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.     

Phophate-induced renal calcification in the rat.

Studies were done to investigate nephrocalcinosis produced in weanling female Wistar rats fed pelleted, semisynthetic diets. The rats were fed diets varying in concentrations of Ca and P supplied as inorganic salts for periods of 4--6 weeks and results compared with control rats fed laboratory rodent chow for the same period of time. Measurement of renal Ca and P concentrations showed that nephrocalcinosis was produced by semisynthetic diets with inorganic phosphate concentrations as low as 0.5% on a weight basis; in contrast, rats fed regular laboratory chow (P = 0.72%) showed no evidence of nephrocalcinosis. The severity of the lesion was proportional to dietary phosphate concentrations from 0.5 to 1.0% but other dietary factors modified the severity of the lesion. With the lower dietary phosphate of 0.5%, increasing dietary Ca from 0.5 to 1.0% decreased the severity of the renal calcification. Decreasing protein concentrations from 25 to 15% casein increased the severity of the renal lesions. Other dietary factors also appear to modify the phosphate-induced nephrocalcinosis since no lesions occurred in rats on laboratory chow. It is suggested that the availability of dietary phosphate may be a factor. The phosphate in the semisynthetic diets was totally inorganic while the natural foods of laboratory chow contain, at least in part, organic phosphate.