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[Variations in the pattern of ruminal volatile free fatty acids, acetoacetate and glucose in the blood plasma of lactating cows after a period of fasting and renewed feeding].

3 lactating cows were fasted for 4 days and then again received food. The trial was performed to investigate the effect of fasting on the concentration and molar proportion of volatile fatty acids in the rumen, on the concentration of free fatty acids and glucose in blood plasma and on the acetoacetate concentration in the blood. Fasting produced a considerable decrease in the total concentration of volatile fatty acids. Processes of ruminal fermentation were characterized, during the fasting period, by a continuous increase in the molar proportions of acetic acid, isobutyric acid and isovaleric acid whereas a significant decline observed to occur in the molar proportions of propionic acid and butyric acid. The reciprocal behaviour of acetate and propionate under conditions of fasting lead to a linear increase in the C2 to C3 ratio from 4.4 : 1 to 9,6 : 1. With renewed food supply all fermentation data returned to normal levels. The concentrations of blood glucose declined after 24 hrs of fasting, remained at the same level for the following 2 days and rose again to normal values on the 4th day of fasting. The concentration of acetoacetate decreased significantly on the first day of fasting to values that were 4 times as high as the initial value. The concentration of free fatty acids in blood plasma increased tremendously to a value 40 times as high as that observed at the beginning of the fasting period. It proved to be a good indicator for the energy requirements of the organism.

Acetoacetates↗

A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance (P=10-9). rs3757840 was also highly significantly associated with fasting glucose (P=8x10-7), but haplotype analysis revealed that this is explained by linkage disequilibrium (r2=0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g) increase in offspring birth weight (P=.002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

Adult↗

Alterations in lymphocyte subsets and pituitary-adrenal gland-related hormones during fasting.

We investigated changes in the immunoendocrine system during fasting. Ten hospitalized patients aged 14-46 y with psychosomatic disorders fasted for 7 or 10 d. Blood samples were collected before and on days 3 and 7 of the 7-d fasts. When fasting continued to 10 d, an additional sample was taken on day 10. We measured blood cellularity (white blood cells and total lymphocytes), the total number and percentage of lymphocyte subsets (CD2, CD3, CD4, CD8, and CD19), natural killer (NK) cell activity, cytokines (interleukin 1 beta, interleukin 2, interleukin 6, granulocyte-macrophage colony stimulating factor, tumor necrosis factor alpha, and interferon gamma), and soluble interleukin 2 receptors. Corticotropin, cortisol, and dehydroepiandrosterone sulfate (DHEAS) concentrations were also determined. Although the total number of lymphocytes decreased during fasting, NK cell activity increased significantly. Plasma cortisol and DHEAS concentrations also increased significantly whereas changes in corticotropin concentrations were not significant. The total number and percentage of CD4 cells decreased significantly during fasting but no other lymphocyte subsets changed significantly. The percentage of CD4 cells was negatively correlated with cortisol concentrations during fasting. No detectable changes occurred in cytokines or soluble interleukin 2 receptors during the study. All measured immunoendocrine values that changed during fasting returned to prefasting values during the refeeding period. These findings indicate that fasting affects immune variables such as T cell subsets and NK cell activity at least in part through changes in adrenal gland-related hormones.

Adolescent↗

Fasting during promotion, but not during initiation, enhances the growth of methylnitrosourea-induced mammary tumours.

The purpose of this work was to investigate the effect of fasting on the induction and growth of chemically-induced mammary carcinogenesis. Female Sprague-Dawley rats were given methylnitrosourea (MNU) i.p. (50 mg/kg) at 50 days of age; a group of rats were exposed to 4 day fasting followed by 1 day of refeeding before the administration of the carcinogen, while another group was exposed to three cycles of 3 days fasting in 10 days, beginning 1 week after MNU injection. Fasting enhanced the development of mammary tumours only in rats fasted after carcinogen damage, while it did not affect the induction of tumours in rats fasted before MNU, if compared with full-fed controls. The enhanced growth of mammary tumours sustained by fasting during promotion was observed in the cervical-thoracic region. In addition, exposure to fasting made rats susceptible to the development of MNU-induced extra-mammary cancers. Different from the preventive effect of caloric restriction on tumor development, these data demonstrate that fasting affects the promotion phase of carcinogenesis by enhancing the growth of MNU-induced mammary tumours.

Adenocarcinoma↗

The effects of fasting on body composition, glucose turnover, enzymes and metabolites in the chicken.

Chickens (1,200 g) were fasted 1, 4, or 8 days. Significant decreases occurred in total body protein and fat with fasting, with the greatest energy loss from fat. Glucose production determined with either [2-3H] or [6-3H] glucose injected simultaneously with [U-14C] glucose remained constant with fasting at 10 to 13 mg/minute/kg body weight which is much higher than reported for mammals. Blood lactate and glycerol were unchanged with fasting, while pyruvate increased and plateaued. Plasma alanine, serine and glycine levels were extremely high compared to values in fasted mammals. Blood beta-hydroxybutyrate increased dramatically with fasting (350 to 3,500 nm/ml), while acetoacetate remained constant. The hepatic lactate: pyruvate ratio was unchanged with fasting, while the beta-hydroxybutyrate:acetoacetate ratio increased. These ratios have been reported to influence phosphoenolpyruvate (PEP) and glucose production in mammals. Hepatic and renal phospyoenolpyruvate carboxykinase (PEPCK) levels remained constant, while hepatic lactate dehydrogenase increased with fasting. Beta-Hydroxybutyrate dehydrogenase levels were very low at all times. The results indicate little glucose sparing adaptation per kg in the fasting chicken.

Animals↗

Growth retardation induced in rat fetuses by maternal fasting and massive doses of ergocalciferol.

The present study was conducted in Wistar rat fetuses to investigate the growth retardation induced by maternal fasting and/or massive doses of ergocalciferol during the third trimester of pregnancy. Growth indices examined in 21-d fetuses were body weight and ossification of sacrococcygeal vertebrae, supraoccipital bone, sternebrae and proximal phalanges in the forepaw stained by alizarin red S. Growth retardation was expressed in hours by comparison with the normal standard development, or in sigma by calculating the relative difference from the control, utilizing the standard variance in normal fetuses. Degrees of growth retardation expressed in the common scales were different among the indices and between fasting and massive doses of ergocalciferol; body weight and ossification of sacrococcygeal vertebrae were most severely retarded by fasting and least by ergocalciferol. Ossification of sternebrae was moderately retarded by fasting and by ergocalciferol, and ossification of supraoccipital bone was moderately retarded by fasting but not by ergocalciferol. Ossification of proximal phalanges in the forepaw was least retarded by fasting and most severely retarded by ergocalciferol. The observed retardations were progressions relatable to the duration of fasting. Combined treatments of fasting and ergocalciferol showed more deleterious effects on growth than fasting only or ergocalciferol only and induced face anomalies, "carnival fetuses." These findings show that growth retardations induced by different nutritional disturbances may vary among indices and that comparisons of various indices are important in the analysis of teratological experiments.

Animals↗

Increase in fasting insulin and glucose over seven years with increasing weight and inactivity of young adults. The CARDIA Study. Coronary Artery Risk Development in Young Adults.

To characterize 7-year changes in fasting serum insulin and glucose concentrations, the authors analyzed population-based data on 3,095 nondiabetic black and white men and women who were initially aged 18-30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Measurements were made of fasting insulin (by an assay with little cross-reactivity to proinsulin) and fasting glucose on frozen samples from baseline and Year 7 examinations. Over the 7-year period, mean fasting insulin increased 10-25%, mean fasting glucose increased 7-10%, and mean body mass increased 7-12% across the four race-, sex-groups. The strongest predictor of both insulin increase and glucose increase was an increase in body mass over the 7 years. Adjusted for age and examination time period in race-, sex-specific repeated measures analyses, fasting insulin increased longitudinally by approximately 5 microU/mL per 5 kg/m2 increase in body mass index (p < 0.05). Adjusted for age and time period, fasting insulin increased over the 7 years by approximately 2.5 microU/mL per 0.08 unit increase in waist/hip ratio (p < 0.05), although this association was much stronger cross-sectionally. In a similar model, each 100 unit decrease in physical activity longitudinally predicted a 0.1-0.2 microU/mL increase in fasting insulin (p < 0.05 in black men only); this association was stronger and statistically significant in all race-, sex-groups cross-sectionally. Fasting insulin was not associated with energy intake either cross-sectionally or longitudinally, but age- and time-adjusted associations of insulin change with change in several nutrients (e.g., energy from fat) were statistically significant in whites. The authors conclude that marked increased in weight in young adulthood adversely alters glucose and insulin metabolism, and that, if not reversed, this may lead to harmful health consequences in later life.

Adolescent↗

Systemic but not intraovarian concentrations of insulin-like growth factor-I are affected by short-term fasting.

To determine whether systemic and/or intraovarian concentrations of insulin-like growth factor-I (IGF-I) are affected by short-term fasting, 24 heifers were blocked by weight and, within block, were assigned to one of three treatments: fasted for 0 h (controls; n = 8), fasted for 24 h (n = 8), or fasted for 48 h (n = 8). Blood plasma was collected every 8 h from -64 h to 0 h before ovariectomy (OVEX). OVEX was performed per vagina under local anesthesia during the follicular phase of an estrous cycle (36-42 h after synchronization with prostaglandin-F2 alpha). Follicular fluid (FFL) and granulosa cells were collected individually from follicles greater than or equal to 6 mm (large), and FFL was pooled from follicles 1.0-5.9 mm (small) in diameter. Fasting did not affect (p greater than 0.20) the number (mean +/- SE) of small (52 +/- 7) or large (1.5 +/- 0.4) follicles per heifer, specific binding of 125I-hCG to granulosa cells of follicles greater than or equal to 8 mm in diameter, or concentrations of progesterone in FFL of small follicles. At OVEX, body weight was less (p less than 0.01) for 24 h- and 48 h-fasted heifers (412 +/- 7 kg and 399 +/- 7 kg, respectively) than for 0 h-fasted heifers (442 +/- 7 kg). At OVEX, plasma concentrations of IGF-I were lower (p less than 0.05) in the 48 h-fasted group (105 +/- 8 ng/ml) than in the 0 h-fasted group (140 +/- 8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Central infusion of recombinant ovine leptin normalizes plasma insulin and stimulates a novel hypersecretion of luteinizing hormone after short-term fasting in mature beef cows.

The present studies tested the hypotheses that short-term fasting would reduce leptin gene expression and circulating concentrations of leptin and insulin in mature, ovariectomized, estradiol-implanted cows and that intracerebroventricular infusions of recombinant ovine leptin (oleptin) would attenuate reductions in insulin concentration and stimulate LH secretion. Ovariectomized cows were assigned to either control (normal fed; n = 6) or fasted (60 h of fasting; n = 7) groups and infused with 200 microg recombinant oleptin three times at hourly intervals on Day 2 (n = 6 per group). Fasting decreased plasma concentrations of insulin (P < 0.01) and leptin (P < 0.04) but, as expected, did not reduce plasma concentrations of glucose or any LH secretion variable. Central infusion of leptin on Day 2 increased (P < 0.01) plasma concentrations of leptin in both control and fasted groups. Concomitantly, leptin treatment increased plasma insulin (P < 0.01) and LH (P < 0.03) concentrations in fasted but not in control cows. Increases in overall mean and baseline concentrations of LH after leptin treatment were the result of an augmentation of the size of LH pulses. The effects of fasting on leptin gene expression and the potential diurnal effects on circulating leptin were examined in a group of cows (n = 12) not treated with leptin. Fasting for 60 h reduced (P < 0.001) leptin gene expression by 30%, and no diurnal effects on circulating leptin were observed. These results indicate that although short-term fasting does not reduce the frequency or amplitude of LH pulses or the concentration of LH in mature cows, this nutritional perturbation clearly sensitizes both the hypothalamic-pituitary axis and endocrine pancreas to exogenous leptin, which in these experiments resulted in heightened secretion of both LH and insulin.

Adipose Tissue↗

Duration of preoperative fast correlates with arterial blood pressure response to halothane in infants.

UNLABELLED: In this study, we sought to determine whether the duration of preoperative fasting affects the decrease in blood pressure observed in infants and children during halothane anesthesia. Two-hundred-fifty pediatric patients were divided into 5 age groups: term neonates (n = 50), 1-6 mo (n = 50), 6-24 mo (n = 50), 2-6 yr (n = 50), and 6-12 yr (n = 50). After anesthetic induction with halothane, end-tidal halothane was maintained at 2 minimum alveolar anesthetic concentration (MAC) for 10 min to allow myocardial uptake. Patients were grouped by duration of preoperative fast (0-4 h, 4-8 h, 8-12 h, and >12 h). Changes in heart rate and systolic (SAP) and mean (MAP) arterial blood pressure from preinduction to 2 MAC were compared among fasting groups within each age group. In the 1- to 6-mo age group, the changes in SAP and MAP were significantly greater in infants fasting 8-12 h than in those fasting 0-4 h (SAP, -51 mm Hg versus -31 mm Hg, respectively; MAP, -48 mm Hg versus -32 mm Hg; P < 0.05). No statistically significant differences were noted in the older age groups. The results of this study demonstrate that prolonged preoperative fasting is associated with a greater decrease in blood pressure in infants. This exacerbation of the already significant hemodynamic depression observed in infants during halothane anesthesia underscores the importance of adherence to published fasting guidelines. IMPLICATIONS: We studied changes in blood pressure during halothane anesthesia in infants and children and found that blood pressure decreased to a greater extent in infants who fasted for longer than 8 h before surgery. This exacerbation of the already significant hemodynamic depression observed in infants during halothane anesthesia underscores the importance of adherence to published fasting guidelines.

Anesthetics, Inhalation↗

Response of the pancreas to fasting: adult versus neonates.

The results presented show striking differences in the response of the exocrine pancreas to fasting in suckling versus adult rats. In adult rats, fasting led to an increase in lipase to amylase ratio with a particularly sharp decrease in amylase concentrations, a generalized decrease in total protein, amylase, trypsinogen and lipase contents, and a decrease in responsiveness of the pancreatic acini to optimal and supraoptimal concentrations of secretagogues in vitro. In 15 day old pups, however, fasting led to an increase in total amylase, trypsin and lipase and a maintenance of the total protein content in their pancreases. Further, no decrease in responsiveness of their pancreatic acini to secretagogue stimulation is observed at the concentrations studied. The difference in the behavior of the exocrine pancreas during fasting can be partly explained by the changing pattern of their responses to hormonal stimulation, particularly that of corticosterone and cholecystokinin during various stages of development. Fasting led to an increase in corticosterone and presumable decrease in cholecystokinin. The pancreas of the suckling rat is very sensitive to the induction effect of corticosterone while that of the adult rats is relatively insensitive. Conversely, the pancreas of the adult rats is sensitive to the trophic effect of cholecystokinin while that of the suckling rat has the opposite reaction. The combination of these and other factors then resulted in an entirely different profile of the responses of the exocrine pancreas to fasting. Recent studies in our laboratory, and that of others, showed that an analogous situation also existed in the small intestine. Fasting of adult rats led to a general decrease in small intestinal enzymes including sucrase and maltase (29) but in suckling rats led to (30,31) increases of sucrase and maltase. Corticosterone again has been shown to be involved (30,31). Further, the small intestinal sucrase of the suckling rats responded to corticosterone by an increase in its level but the same hormone did not seem to control the sucrase concentrations in the small intestine of adult rats (32,33). Thus, both the small intestine and the pancreas responds very differently to fasting presumably mediated through a varying pattern of responses to selective hormonal stimulation, eg in this case, corticosterone. These results strongly suggest the importance of the interaction between environmental influences (fasting in this case) and the stage of development in determining the outcome of ontogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Amylases↗

Iodide administration enhances thyrotrophin responsiveness to thyrotrophin-releasing hormone during fasting: evidence for normal pituitary feedback regulation.

Short-term fasting in humans is associated with diminished delta TSH to TRH. The purposes of the present study were to reassess basal TSH levels and TRH responsiveness during fasting utilizing a sensitive radioimmunoassay (RIA: sensitivity 0.3 microU/ml; normal range 0.66-2.98 microU/ml) and to determine if normal feedback regulation is maintained during the fasting state. Eight control subjects (C) and six iodide-treated (I) subjects (262 mg/d) were studied in the fed state and on day 10 of fasting. T3, T4, and TSH were measured by RIA, and free T4 and free T3 by equilibrium dialysis. Basal serum TSH levels in the control group were 2.0 +/- 0.3 microU/ml (mean +/- SEM) in the fed state and increased to 14.7 +/- 3.5 microU/ml 20 min after TRH administration. The fasting basal TSH level of 1.6 +/- 0.3 microU/ml was significantly decreased (P less than 0.01) compared to control, as was the level of 8.8 +/- 2.3 microU/ml (P less than 0.01) obtained 20 min after TRH. In the iodide-treated group the basal TSH level was 1.4 +/- 0.2 microU/ml during feeding which increased (P less than 0.025) to 2.9 +/- 0.7 microU/ml during fasting; the TSH value 20 min after TRH was 12.6 +/- 2.5 microU/ml while feeding and 17.3 +/- 2.9 microU/ml while fasting. Free and total T3 decreased during fasting in both groups. Total T4 was unchanged between the fed and fasted periods in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Fasting↗

Influence of glucagon on natriuresis and glucose-induced sodium retention in the fasting obese subject.

The role which glucagon could play in the mechanism of fasting natriuresis and renal sodium retention associated with carbohydrate refeeding was studied in thirty-seven non-diabetic obese subjects. In nine obese subjects undergoing a 7 day fast without any additional treatment (control group), the renal sodium excretion exceeded intake through the whole experimental period, with maximal natriuresis on day 2 of the fast. Blood glucose and plasma insulin (IRI) levels fell rapidly from the first day of fast on, while pancreatic glucagon (IRG) titres rose from day 1 to day 4, declining slightly thereafter. When additional subjects received intravenous glucose on day 4 (n = 6), there was a rise in blood glucose concentration and in IRI associated with a rapid drop in IRG restricted to the period of glucose infusion. The resulting antinatriuresis occurred essentially during the following 36 h, while IRG and IRI levels had returned to fasting levels. A comparable glucose load on day 4 associated with 0.1 mg glucagon (n = 5) still led to the glucose-induced antinatriuresis while 1 mg glucagon added to a similar glucose infusion completely abolished its antinatriuretic effect (n = 6). Glucagon infused alone on day 4 of fast aggravated fasting natriuresis (n = 5) but was devoid of this effect when administered 24 h after the glucose load (n = 6). These data indicate that fasting hyperglucagonaemia or its reduction upon glucose refeeding, cannot be considered as directly involved in renal mechanism(s) responsible for fasting natriuresis of antinatriuretic effects of carbohydrate. It is suggested that the role of glucagon is indirect, possibly through its influence on ketogenesis which in turn may alter renal sodium handling.

Adult↗

Tissue-specific regulation of lipoprotein lipase in humans: effects of fasting.

BACKGROUND: We have previously reported that the activity of lipoprotein lipase (LPL) measured in postheparin plasma from humans fasted for 30 h is increased relative to the fed state. This is in contrast to laboratory animals, where the strong down-regulation of LPL in their adipose tissue on fasting is reflected in decreased levels of LPL activity in postheparin plasma. MATERIALS AND METHODS: To search for the tissue source of the increase in LPL activity on fasting of humans, young, healthy subjects were fasted for 10, 20 or 30 h, and LPL was measured in plasma (pre- and postheparin) and in biopsies from subcutaneous adipose tissue (abdominal) and from a skeletal muscle (tibialis anterior). Both LPL activity and LPL protein mass were measured in the tissue homogenates. Values after fasting were compared with values from postprandial samples obtained 2 h after a meal. RESULTS: Fasting for up to 30 h did not alter LPL activity in basal plasma (preheparin). LPL activity in postheparin plasma remained unchanged after 10 and 20 h of fasting, but was increased by 50% after 30 h (P < 0.05). Ten hours of fasting caused a 25% (P < 0.05) decrease in LPL activity in subcutaneous adipose tissue, while LPL activity in skeletal muscle remained unchanged. After 30 h of fasting, both LPL activity and mass had decreased by approximately 50% (P < 0.05) in adipose tissue, but had increased by approximately 100% (P < 0.05) in muscle. CONCLUSIONS: The increase in postheparin plasma LPL activity after 30 h of total food deprivation of healthy human subjects seemed to reflect an increased activity and mass of LPL in skeletal muscle.

Adipose Tissue↗

Elevated fasting triglycerides predict impaired glucose tolerance in adolescents at risk for type 2 diabetes.

OBJECTIVE: The aim of this study was to evaluate whether fasting laboratory values can predict impaired glucose tolerance (IGT) in adolescents who are at risk for developing type 2 diabetes mellitus (T2DM). HYPOTHESIS: Elevated fasting triglycerides, a marker for worsening insulin resistance, predict risk for IGT. DESIGN: Following a fast of at least 9 h, laboratory measures, body mass index (BMI), and demographic information were obtained. The subjects then underwent a 75-g oral glucose challenge with a 2-h postchallenge glucose determination. SUBJECTS: Eighty-four adolescents aged 12-20 yr with at least two risk factors for developing T2DM (obesity, family history of T2DM, or acanthosis nigricans) and with either a fasting insulin level > or =25 microU/mL or a homeostasis model assessment of insulin resistance (HOMA-IR) > or =3.5 were recruited for the study. RESULTS: Ten subjects (12%) had IGT [2-h glucose > or =140 mg/dL (7.77 mmol/L)], and 10 subjects (12%) had impaired fasting glucose [IFG; fasting glucose > or =100 mg/dL (5.55 mmol/L)]. However, only three (30%) subjects with IGT had IFG, though all subjects with IGT had a fasting triglyceride level > or =150 mg/dL (1.70 mmol/L). Of those subjects with elevated triglycerides, 29% had IGT. As a screening test to predict risk for IGT, elevated triglycerides >150 mg/dL had a sensitivity of 100% and a specificity of 68%. The positive predictive value was 29%, and the negative predictive value was 100%. CONCLUSIONS: Screening with fasting glucose alone would have missed 70% of subjects with IGT in this population of insulin-resistant adolescents. However, a fasting triglyceride level > or =150 mg/dL was strongly associated with IGT and may help to identify at-risk adolescents who should undergo formal glucose tolerance testing.

Adolescent↗

Characterisation of fast, slow and cardiac muscle tropomyosins from salmonid fish.

Tropomyosin (TM) has been isolated from the cardiac muscle, and fast and slow trunk (myotomal) muscles of the mature salmonid fish Atlantic salmon (Salmo salar) and rainbow trout (Salmo gairdneri). When examined electrophoretically, isoforms of TM were detected which were specific, and exclusive, to each type of muscle. Cardiac and fast muscles contained single and distinct isoforms, while slow muscle contained two distinct isoforms, closely related in terms of apparent M(r), and pI. There was no detectable difference between the same TM type from either salmon or trout. On a variety of gel systems, the cardiac and slow isoforms migrated in close proximity to each other and to rabbit alpha-TM. The fast isoform comigrated with rabbit beta-TM. In developing salmon fry, a more acidic (unphosphorylated) variant of TM was present in addition to, and of similar M(r) to, the fast adult isoform. This TM declined in steady-state level during maturation and was virtually undetected in adult muscle. All of the isolated TMs contained little or no covalently bound phosphate and were blocked at the N-terminus. The amino acids released by carboxypeptidase A, when ordered to give maximal similarity to other muscle TMs, were consistent with the following sequences: fast (LDNALNDMTSI) and cardiac (LDHALNDMTSL). The C-terminal region of the slow TM contained His but was heterogeneous. In viscosity measurements, performed as a function of increasing protein concentration, at low ionic strength (t = 5 degrees C, pH 7.00), fast TM exhibited the highest relative viscosity values. Lower and equivalent levels of polymerisation occurred with the cardiac and slow TMs. Polymerisation of all three isoforms was temperature-dependent, with cardiac TM being least sensitive and fast TM being most sensitive. Determination of the complete coding sequence of adult fast TM confirmed the findings of the carboxypeptidase analysis, but the remainder of the sequence more closely resembled alpha-type TMs than beta-type TMs. Overall, salmon fast TM contains 20 (mostly conservative) substitutions compared to rabbit striated muscle alpha-TM and 40 (mostly conservative) substitutions compared to rabbit striated muscle beta-TM. This demonstrates that electrophoretic mobility is not, in all instances, a suitable method to assess the isomorphic nature of striated muscle TMs.

Amino Acid Sequence↗

Metabolic profiles and bile acid extraction rate in the liver of cows with fasting-induced hepatic lipidosis.

This study was designed to monitor lipid profile in the portal and hepatic blood of cows with fasting-induced hepatic lipidosis, and to compare the results with those in the jugular blood. The work was also carried out to investigate bile acid (BA) in these vessels, and further to investigate BA extraction rate in the liver. Five cows were equipped with catheters in the portal, hepatic and jugular veins (day 0), fasted for 4 days (day 1-day 4) and then refed (day 5-day 11). Before morning feeding, blood was sampled before, during and after fasting from the catheterized vessels. In the portal blood, the concentration of non-esterified fatty acids (NEFA) showed a progressive increase and at day 5 there was an approximate twofold rise. Increased NEFA concentrations were also found similarly in the other two veins. At day 5, beta-hydroxybutyrate (BHBA) in the portal, hepatic and jugular blood rose to 197, 190 and 186% of the pre-fasting value, respectively. However, the concentrations of NEFA and BHBA in the three veins gradually returned to pre-fasting concentration during the refeeding period. Compared with the pre-fasting value at day 0, the content of liver triglyceride (TG) increased significantly at day 5 (P < 0.01). In the liver, the hepatic extraction rate of BA dropped from 3.1 times pre-fasting to 2.2 times during fasting. There were no significant differences in the concentrations of glucose, TG, total cholesterol, cholesterol esters, free cholesterol and phospholipids. The results of the current study show that metabolic alterations occur in the portal, hepatic and jugular veins during induction of hepatic lipidosis in cows, and mostly metabolites, with exception of BA concentration, run parallel. The decreased BA extraction rate in the liver of fasted cows was considered to reflect hepatic cell impairment caused by TG accumulation. Hopefully, the findings, at least in part, contribute to the explanation of the pathophysiology of hepatic lipidosis in dairy cows.

Animals↗

Down-regulation of urinary AQP2 and unaffected response to hypertonic saline after 24 hours of fasting in humans.

BACKGROUND: In rats, 24 hours of fasting impairs urinary concentrating ability by down-regulation of aquaporin-2 (AQP2). We tested the hypothesis that 24 hours of fasting in humans reduces the capability to form AQP2 and impairs the antidiuretic response to hypertonic saline infusion. METHODS: In a crossover study of 14 healthy subjects, the effect of 24 hours of fasting was compared to a nonfasting control experiment on urinary excretion of AQP2 (u-AQP2), free water clearance (C(H(2)O)), plasma arginine vasopressin (AVP), urinary cyclic AMP (u-cAMP), and natriuretic peptides. The following response to 3% sodium infusion was measured using the same effect variables. U-AQP2, AVP, and u-cAMP were determined by radioimmunoassays. RESULTS: Fasting during 24 hours reduced u-AQP2 (14%), increased AVP (30%) despite a reduction in serum osmolality (P < 0.05), and depleted volume. C(H(2)O) and urine volume were not reduced, thus relatively increased after fasting. u-cAMP was not significantly different between the two procedures. Three percent saline resulted in the same relative increases in AVP, serum osmolality, u-AQP2, and u-cAMP and decreases in C(H(2)O) and urine volume independently of fasting. The reduced u-AQP2 and increased AVP after fasting were maintained during and after saline infusion. CONCLUSION: Twenty-four hours of fasting decreased u-AQP2 and reduced urine osmolality likely as a result of decreased sensitivity of collecting duct cells to AVP. Fasting-related insensitivity of collecting duct cells to AVP was restored by 3% saline infusion. Finally, after saline infusion, other factors such as the increased plasma atrial natriuretic peptide (p-ANP) levels could contribute to the u-AQP2 regulation.

Adult↗