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Nutrition and somatomedin. XXII: Molecular regulation of insulin-like growth factor-I during fasting and refeeding in rats.

The liver is thought to be the locus of nutritional/hormonal regulation of circulating insulin-like growth factor-I (IGF-I). To probe the basis of nutritional regulation, we examined changes in serum IGF-I, hepatic content of extractable IGF-I immunoreactivity (a high Mr putative precursor) and hepatic IGF-I mRNA during fasting and refeeding in rats. Preliminary studies revealed that the hepatic level of IGF-I mRNA was consistently reduced only after food was withheld for 3 days, so the effects of refeeding were subsequently examined in such animals. After 3 days of fasting, animals lost 30% of their initial weight; weight regain was apparent within 3 h of refeeding ad libitum and, after 48 h, weight was comparable to initial fed levels. Fasting reduced levels of serum and extractable hepatic IGF-I to 19 and 26% of control (fed) values respectively (both P less than 0.005 vs control). There was no change in levels of serum IGF-I over the first 3 h of refeeding, but IGF-I rose above fasted levels at both 9 and 48 h (both P less than 0.005). Extractable hepatic IGF-I rose more slowly and was still below fasted levels after 9 h of refeeding, and modestly, but not significantly, greater than fasted levels after 48 h. The ratio of serum to hepatic IGF-I was decreased compared with control after 3 days of fasting, but increased after 3 and 9 h of refeeding (P less than 0.02 at 9 h). Northern blot analysis of total hepatic RNA revealed four species of IGF-I mRNA 0.8-1.1, 2.0, 4.0 and 7.5 kb in size. Each mRNA species fell to 15-28% of control levels after 3 days of fasting (all P less than 0.001). There was a prompt increase in each transcript after 3 h of refeeding, and all values were significantly (P less than 0.05) greater than fasted levels at 9 h but, at 48 h, most species were still below control levels. Levels of mRNA for the cytoskeletal proteins beta-actin and cyclophilin also fell with fasting, but were restored more rapidly than IGF-I mRNA, to or above control levels after 3 h of refeeding. The observation that IGF-I expression was decreased at 3 h when beta-actin and cyclophilin were normalized suggests specificity of regulation. Despite the temporal incongruity between IGF-I mRNA and serum and hepatic IGF-I, there were highly significant correlations (all P less than 0.002) between each pair of parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗

The effect of a 72-h fast on plasma levels of pituitary, adrenal, thyroid, pancreatic and gastrointestinal hormones in healthy men and women.

Seventeen human subjects fasted without electrolyte replacement for 3 days and hormone levels were measured before, during and after the fast. Immediate consequences of the fasting state in healthy human subjects include a marked increase in plasma cortisol. ACTH, beta-endorphin, beta-lipotrophic hormone, adrenaline, noradrenaline and dopamine. Levels of all these hormones were much greater on the first morning of the fast than in the post-prandial state, even though the plasma glucose level was no lower than that observed on the morning before the fast began. A clear fall in TSH and tri-iodothyronine (T3) levels was observed, but thyroxine levels did not change significantly. Insulin levels fell whereas proinsulin levels did not fall during the fast, though they did rise markedly upon re-feeding. An increase in GH levels was particularly apparent in male subjects, but was also seen in females when evening samples were compared. Pancreatic glucagon showed a modest rise during the fast, but fell again on refeeding; total glucagon also rose as the fast proceeded, but increased markedly upon re-feeding. Levels of gastrin and peptide YY remained low during the fast. Plasma electrolyte levels were unchanged. The following were closely correlated: cortisol with ACTH, T3 with log10 TSH, dopamine with noradrenaline, and (negatively, during the fast) pancreatic glucagon with glucose.

Adrenal Cortex Hormones↗

Glucose-induced insulin secretion from islets of fasted rats: modulation by alternate fuel and neurohumoral agonists.

Islets from fed and 24-h-fasted rats were studied immediately after collagenase isolation. (1) After a 24-h fast, the insulin secretory responses to 8 mM glucose measured during perifusion were reduced by more than 90% from islets of fasted donors. (2) Increasing glucose to 11 or 27.5 mM resulted in enhanced insulin secretion from islets of fasted animals. (3) Fasting did not reduce islet insulin content. (4) Responses to 8 or 27.5 mM glucose were not affected if fatty acid-free albumin was used during the perifusion. (5) Inclusion of alpha-ketoisocaproate (5 mM), monomethyl succinate (10 mM) or carbachol (10 microM) significantly amplified insulin release from fasted islets in the simultaneous presence of 8 mM glucose. (6) Phospholipase C activation by glucose, carbachol or their combination was not adversely affected by fasting. (7) The response to the protein kinase C activator, phorbol 12-myristate 13-acetate (500 nM), was reduced by about 60% after fasting. (8) Extending the fast to 48 h resulted in a severe decline in response to 11 mM glucose; however, the further addition of 10 microM carbachol still enhanced release from these islets. The results confirm that caloric restriction impairs islet sensitivity to glucose stimulation and that protein kinase C may be involved in the reduction of glucose-induced insulin release from these islets. The activation of phospholipase C by cholinergic stimulation may contribute to the maintenance of insulin secretion from calorically restricted animals. These results also demonstrate that free fatty acids are not essential for glucose to evoke secretion from isolated islets of fasted donors.

Analysis of Variance↗

Decreased response of mobile calcium in pancreatic islets of fasted rats to glucose stimulation and calcium manipulation.

The effect of fasting on mobile calcium in the B-cells of rat pancreatic islets was investigated in view of a possible role of calcium in the fasting-induced impairment of insulin secretion. Mobile calcium (GBHA-Ca), an ionized or readily ionizable calcium fraction, was determined histochemically with glyoxal bis (2-hydroxyanil). Fasting (24-72 h) strongly decreased the GBHA-Ca content of islets in situ (55-60%). Incubation of isolated islets at 2.5 mM glucose in the presence of 2.5 mM Ca2+ resulted after 15 min in stable GBHA-Ca levels, which were 25% lower in fasted than in fed islets. Glucose (15 mM) caused the GBHA-Ca content of fed islets to decrease rapidly and to rise again after 30 min. These changes did not occur after 24 or 72 h of fasting. GBHA-Ca appeared not to be displaceable with La3+. At 2.5 mM glucose, withdrawal of Ca2+ rapidly reduced GBHA-Ca in fed and fasted islets. Glucose (15 mM) inhibited this rapid fall, and this inhibitory effect was particularly evident in fed islets. Washing and preincubation in the absence of Ca2+ (2.5 mM glucose) largely depleted fed and fasted islets of GBHA-Ca. Reintroduction of Ca2+ at 2.5 mM glucose only partially restored the GBHA-Ca levels of fed and fasted islets. By contrast, 15 mM glucose restored the characteristic pattern of GBHA-Ca in fed islets as seen in nondepleted islets, but in fasted islets at lower levels as previously seen. Thus, fasting decreased the GBHA-Ca content and its response to glucose stimulation. It is suggested that GBHA-Ca, which is presumably mainly localized in the secretory granules, plays a role in the initiation of insulin secretion.

Animals↗

Fasting plasma glucose in screening for diabetes in the Taiwanese population.

OBJECTIVE: To reveal the relationship between fasting and 2-h postload plasma glucose and to examine the appropriate fasting glucose cutoff as the primary screening test for diabetes. RESEARCH DESIGN AND METHODS: We recruited 5,303 subjects from preventive services of the National Cheng Kung University Hospital. Exclusion criteria were age <20 years, pregnancy, known diabetes, and a history of recent surgery, trauma, or illness. All subjects received the 75-g oral glucose tolerance test. The relationship between fasting and 2-h glucose was examined. Sensitivities, specificities, efficiency, and predictive values were assessed at different cutoffs of fasting glucose for prediction of diabetes. RESULTS: The best fit model for the relationship between fasting and 2-h glucose was fasting glucose = 4.914-0.060 x (2-h glucose) + 0.0144 x (2-h glucose)2. From this model, the fasting glucose was 6.0 mmol/l when 2-h glucose was 11.1 mmol/l. A fasting glucose with 6.25 mmol/l gave the same diabetes prevalence as the World Health Organization 2-h glucose criterion. When 7.8 mmol/l was the fasting glucose cutoff, the sensitivity was 28.5%. Lowering the cutoff from 7.8 to 7.0 mmol/l increased the sensitivity by 11.2% and slightly reduced the specificity and positive predictive value. If the cutoffs were 6.25 and 6.0 mmol/l, the sensitivity increased and the specificity and the positive predictive value decreased accordingly. CONCLUSIONS: Our results suggest that fasting glucose as a screening criterion for diabetes could be revised downward to 7.0 mmol/l, because the slight reduction of positive predictive value was more than balanced by an apparent increase of sensitivity and insignificant change of specificity.

Adult↗

Effects of age on fasting-induced changes in insulin, glucose, urea nitrogen, and free fatty acids in sera of sheep.

The hypothesis that prepubertal ewe lambs are metabolically different from postpubertal ewes was tested. Ovariectomized ewes (4 years of age; n = 4) and lambs (6 months of age; n = 4) were fasted for 72 hr. Serum concentrations of insulin, glucose, urea nitrogen, and free fatty acids (FFA) were measured in blood samples taken at 6-hr intervals between 30 hr before and 72 hr after feed removal. Serum concentrations of urea nitrogen and glucose were not different (P greater than 0.20) between age groups before fasting. Serum concentrations of insulin in ewes increased toward the end of the prefast period whereas those in lambs did not (age x time, P less than 0.01). Serum concentrations of FFA in ewes tended to be lower (P less than 0.07) than those in lambs prior to fasting. During fasting, concentrations of insulin decreased (P less than 0.02) over time in ewes and lambs and did so in a similar manner (age x time, P greater than 0.70). Urea nitrogen increased (P less than 0.0001) in both fasted ewes and fasted lambs in a comparable manner (age x time, P greater than 0.20). Concentrations of glucose during fasting were not significantly affected (P greater than 0.90) by age. There was a tendency (P = 0.08) for concentrations of glucose to change over time but the pattern did not appear to be related to fasting. During fasting, concentrations of FFA tended to be higher (P less than 0.07) in lambs than in ewes and increased (P less than 0.0001) in both groups in a similar fashion (age x time, P greater than 0.10). The findings herein suggest that turnover of FFA in lambs may be slightly greater than that in ewes during the fed and fasted states.

Age Factors↗

Impaired fasting glucose and cardiovascular outcomes in postmenopausal women with coronary artery disease.

BACKGROUND: Type 2 diabetes increases risk for cardiovascular disease. Persons with impaired fasting glucose levels may also have increased risk. OBJECTIVE: To evaluate the association between glucose status and cardiovascular outcomes and the effect of lowering the fasting glucose level criterion for impaired fasting glucose from a lower limit of 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL). DESIGN: Prospective cohort study. SETTING: 20 U.S. clinical centers. PATIENTS: 2763 postmenopausal women with established coronary heart disease (CHD) who were followed for 6.8 years. MEASUREMENTS: Any CHD event (nonfatal myocardial infarction or CHD death), stroke or transient ischemic attack (TIA), congestive heart failure (CHF) hospitalization, and any cardiovascular event. RESULTS: During follow-up, 583 women had a CHD event, 329 women had a stroke or TIA, and 348 women were hospitalized for CHF. Women with diabetes were at an approximately 75% increased risk for each outcome compared with normoglycemic women. The 218 women with impaired fasting glucose according to the 1997 definition (fasting glucose level, 6.1 to 6.9 mmol/L [110 to 125 mg/dL]) had increased risk for any CHD event (hazard ratio, 1.37 [95% CI, 1.08 to 1.74]), while the 698 women with impaired fasting glucose according to the 2003 definition (fasting glucose level, 5.6 to 6.9 mmol/L [100 to 125 mg/dL]) were not at increased risk (hazard ratio, 1.09 [CI, 0.90 to 1.34]). Most of the women (n = 480) with fasting glucose levels between 5.6 mmol/L (100 mg/dL) and 6.0 mmol/L (109 mg/dL) had no increased risk for CHD (hazard ratio, 0.90 [CI, 0.73 to 1.12]). Women with impaired fasting glucose according to either definition were not at increased risk for stroke or TIA or CHF. LIMITATIONS: These findings may not be generalizable to men or women without existing heart disease. CONCLUSIONS: Among postmenopausal women with coronary artery disease, the 2003 definition for impaired fasting glucose was not associated with increased risk for new CHD, stroke or TIA, or CHF.

Aged↗

Serum levels of interleukin-6 and dehydroepiandrosterone sulphate in response to either fasting or a ketogenic diet in rheumatoid arthritis patients.

OBJECTIVE: To investigate the effects of either a 7-day fast or a 7-day ketogenic diet upon serum interleukin-6 (IL-6) and dehydroepiandrosterone sulphate (DHEAS) in RA patients. METHODS: We measured serum concentrations of DHEAS and IL-6 in 23 RA patients with active disease, 10 of whom followed a 7-day sub-total fast and 13 of whom consumed a ketogenic diet (isoenergetic, carbohydrate < 40 g/day) for 7 days. Clinical and laboratory variables were measured at baseline, on day 7 and after re-feeding on day 21. Correlation analyses were used to assess the associations between serum IL-6, DHEAS and disease activity variables at each timepoint. RESULTS: Fasting, but not the ketogenic diet, decreased serum IL-6 concentrations by 37% (p < 0.03) and improved disease activity at day 7. Both fasting and the ketogenic diet increased serum DHEAS levels by 34% as compared with baseline (both p < 0.006). Levels of IL-6, but not DHEAS, correlated with several disease activity variables. CONCLUSION: Both fasting and a ketogenic diet significantly increased serum DHEAS concentrations in RA patients. Only fasting significantly decreased serum IL-6 levels and improved disease activity. As the increases in serum DHEAS were similar in response to both fasting and a ketogenic diet, it is unlikely that the fall in serum IL-6 or clinical improvements after fasting were directly related to increases in serum DHEAS. The fasting-induced fall in serum IL-6 may underlie the fall in CRP and ESR observed in RA patients in response to a 7-day fast.

Adult↗

Effects of fasting on aldosterone secretion in ovariectomized rats.

The present study was designed to assess the effect of fasting on aldosterone secretion in ovariectomized (Ovx) rats. Ovx rats were divided into fed (allowed access to food ad libitum) and fasted (deprived of food for 24 hours) groups. The trunk blood of fed and fasted rats was collected after decapitation. In the in vitro study, adrenal zona glomerulosa (ZG) cells from fed or fasted rats were incubated with angiotensin II (Ang II, 10(-6) M), adrenocorticotropic hormone (ACTH, 10(-9) M), or forskolin (an activator of adenylyl cyclase, 10(-6) M) at 37 degrees C for 30 min. The levels of aldosterone in medium and plasma extracts were measured by radioimmunoassay. Results showed that the levels of plasma aldosterone in fasted rats were lower than those in fed rats. There were no significant differences in basal and Ang II-stimulated aldosterone secretion between fed and fasted groups. The increment of aldosterone induced by ACTH in fasted group was significantly less than that in fed group. Administration of forskolin led to a significant increase in aldosterone secretion in both fed and fasted groups. Fasted group had a decreased aldosterone secretion in response to forskolin as compared with fed group. In summary, these results suggest that fasting decreases aldosterone secretion in Ovx rats through a mechanism in part involving a reduction of aldosterone production in response to ACTH, a decreased activity of adenylyl cyclase, and/or an inhibition of post-cAMP pathway in ZG cells.

Adenylyl Cyclases↗

Downregulation of fasting-induced cAMP response element-mediated gene induction by leptin in neuropeptide Y neurons of the arcuate nucleus.

States of increased metabolic demand such as fasting modulate hypothalamic neuropeptide gene expression and decrease circulating leptin levels. This study tested the hypotheses that fasting stimulates gene induction mediated by cAMP response element (CRE)-dependent increases in gene transcription and that fasting-induced decreases in leptin can regulate this CRE-mediated gene induction. Using C57BL/6J mice transgenic for a CRE-lacZ construct, an immunocytochemical study showed that fasting activated reporter gene expression in the hypothalamic arcuate nucleus (Arc) in a small subset of neurons and increased phosphorylation of CRE binding protein. The increase of beta-galactosidase expression caused by fasting was inhibited by a protein kinase A inhibitor, Rp-8-Br-cAMPS, when the compound was microinjected into the medial basal hypothalamus, and enhanced by intraperitoneal injection of selective phosphodiesterase inhibitors. In situ hybridization studies showed that neuropeptide Y (NPY) mRNA levels increased in the Arc during fasting, whereas proopiomelanocortin (POMC) mRNA levels decreased. Double labeling of mRNA and beta-galactosidase immunoreactivity in the fasted brain indicated that the subpopulation of the neurons expressing beta-galactosidase all produced NPY but not POMC. To study the possible involvement of decreased circulating leptin during starvation on CRE-mediated gene induction, leptin was administered intraperitoneally to fasted mice. Leptin significantly attenuated both beta-galactosidase expression and NPY gene expression stimulated by fasting, suggesting that leptin inhibits fasting-stimulated NPY gene expression at least in part through downregulation of CRE-mediated gene induction in the Arc. Leptin-induced modification of CRE-mediated gene induction in the Arc may play an essential role in the central regulation of feeding behavior and energy expenditure.

Animals↗

Blood sugar control among fasting Muslims with type 2 diabetes mellitus in Ilorin.

Fasting in the month of Ramadan represents a recurring annual event in the life of a Muslim. It also represents one of the five pillars around which the Islamic faith revolves making it desirable to even diabetic Muslims if only to live a spiritually fulfilling life. We therefore embarked upon the study of 33 patients with Type 2 Diabetes Mellitus who fasted in the month of Ramadan of 1417 Hijra year (1997 Gregorian) with a view to establishing the effect of fasting on their blood sugar control. This is meant to serve as a framework for establishing a scientific basis for advice to Muslim diabetic patients who may wish to fast in subsequent years. Eight point three percent of patients considered for enrollment signified their non-willingness to fast even after health-education. In the month preceding fasting the mean +/- SD for fasting blood sugar (FBS) was 6.71 +/- 2.81 mmol/L, 6.50 +/- 2.34 mmol/L for the month of Ramadan and 6.93 +/- 2.53 mmol/L for the month after. There was no statistically significant difference between the means for the three months. However, larger percentage of patients (76%) had their fasting blood sugar improved upon during fasting than either before or after. In addition, there was no reported case of acute complication from diabetic emergencies all through the period of the study. Based on these findings, it was concluded that most Type 2 diabetic patients actually do as well, like their normal counterparts during fasting and could be encouraged to do so provided they are clinically stable.

Adult↗

[Metabolism of L-ascorbic, L-dehydroascorbic and 2,3-diketo-L-gulonic acids during a short duration fast in guinea pigs].

Tricolor variety of guinea-pigs, two or three months old, received, without sex distinction L(+)-ascorbic or L(+)-dehydroascorbic acids intraperitoneally injections as 20 mg p. 100 by weight, three or twenty-four hours after starting a forty-eight hours fast. Ascorbic, dehydroascorbic and 2,3 diceto-L-gulonic acids are estimated by the Roe, Mills, Oesterling and Damron differential 2,4-dinitrophenylhydrazin method in whole blood, urines, kidneys and liver. Food absorption during twenty-four hours after the end of the forty-eight hours fast is not suffisant for guinea-pigs regain first state, during this time, especially in their kidneys and liver. Three hours after the beginning of the fast, urinary excretion of the injected acid increases during the first twenty-four hours of fast; at the end of the forty-eight hours fast their kidneys are deficient in ascorbic acid. Twenty-four hours after the beginning of fast, urinary excretion of ascorbic, dehydroascorbic and 2,3-diceto-L-gulonic acids rises importantly, especially when L-ascorbic acid is injected; it is only the quantity of ascorbic acid which increases in their kidneys and liver, its level being higher in their liver. L-dehydroascorbic acid is utilized immediately. L-ascorbic acid is distributed slowly, stored in a reduced form and it prepares the animals to face a prolonged fast. When the animals are injected three hours after the fast begins, it will be protected for forty-eight hours; if it is injected twenty-four hours after the beginning of fast, the animal will be better prepared to face a prolonged state of stress or a fast lasting more than forty-eight hours.

2,3-Diketogulonic Acid↗

The effect of Ramadan fasting on amniotic fluid volume.

OBJECTIVE: This cross-sectional study was carried out to assess the influence of Ramadan fasting on amniotic fluid volume. METHODS: For this purpose 2 groups of fasting (n=28) and non-fasting (n=25) pregnant women were investigated for amniotic fluid index (AFI) and deepest vertical pocket of amniotic fluid in November (Ramadan month) of 2001-2002 in Kerman Prenatal Clinics in Kerman, Iran. Mean of gestational age based on the last menstrual period and ultrasound reports were 29.6 +/- 5.8 week and 29.5 +/- 4.2 week in fasting and non-fasting groups. RESULTS: There was no significant difference between the 2 groups in age, gestational age, gravidity, parity and systolic/diastolic blood pressures. The mean deepest vertical pocket in fasting and non-fasting groups were 65.9 +/- 12.9 mm and 62.7 +/- 6.5 mm and there was no significant difference between the 2 groups in this regard. Mean AFI in fasting group (189.9 +/- 35.9 mm) and in non-fasting group (166.8 +/- 25.3 mm) showed a significant difference (p less than 0.05). CONCLUSION: Based on the results of the present study fasting in Ramadan has no significant effect on the decrease of AFI, deepest vertical pocket and amniotic fluid volume.

Adolescent↗

Sequential changes in lipid metabolism and the fatty acid profile in liver lipids during fasting and sepsis.

The sequential changes in lipid metabolism and in the fatty acid profile of liver lipids during fasting and sepsis were studied. Liver and blood specimens were taken from normally fed rats and from nonseptically and septically fasted rats at 5, 24, and 48 hr. Sepsis was induced by injecting live Escherichia coli bacteria intraperitoneally. Sepsis attenuated the fasting-induced increase in beta-hydroxybutyrate and reduced liver and serum triglycerides at 5 hr. There was a percentage decline in the most abundant fatty acids in neutral lipids, namely oleic (18:1w9) and linoleic (18:2w6) acids. This was seen throughout fasting and septic fasting. These results indicate that 18:1w9 and 18:2w6 are used as energy substrates and are oxidized to beta-hydroxybutyrate during fasting and mainly to carbon dioxide during septic fasting. On the contrary, the most abundant fatty acids in phospholipids, stearic (18:0), arachidonic (20:4w6), and docosahexaenoic (22:6w3) acids, accumulated in neutral lipids and in phospholipids throughout fasting. However, during sepsis this accumulation was reduced in neutral lipids and reversed to a level below that in the fed and fasted state in phospholipids. These results indicate that a disturbance in membrane integrity and function induced by septic fasting may have pathophysiological consequences for lipid metabolism and liver function during sepsis.

Animals↗

Regulation of epidermal growth factor receptor number and phosphorylation by fasting in rat liver.

The binding of 125I-epidermal growth factor (EGF) to microsomal membrane preparations from the livers of rats fasted for 72 h or fed control or high carbohydrate diets was examined to determine whether alterations in nutrient intake could affect the EGF receptor system. Fasted rats had 40-50% less membrane binding than did control or carbohydrate-fed rats. Scatchard analysis of the binding data indicated that the decrease in EGF binding in fasted rats was due to a decrease in receptor number with no change in receptor affinity. Cross-linking of 125I-EGF to EGF receptors with disuccinimidyl suberate revealed specific binding of a Mr 170,000 protein, which was diminished by approximately 75% in fasting, and a Mr = 150,000 protein, which accounted for 40-50% of the total labeling in the control and carbohydrate-fed rats and which was relatively unchanged by fasting. The sum of the labeling of the 2 bands was reduced by approximately 40% in fasting and is consistent with the reduction in EGF binding detected by Scatchard analysis. EGF stimulated a 1.5-3-fold increase in 32P incorporation into one major protein of 170 kDa in all 3 groups. Basal and EGF-stimulated autophosphorylation of 170 kDa, when normalized for protein, was 75% lower in membranes from fasted animals, compared to those from control or carbohydrate-fed rats. The comparable reduction of 125I-EGF binding to, and 32P incorporation into, the 170-kDa EGF receptor protein suggested that kinase activity/receptor was unaffected by fasting. Moreover, EGF receptor kinase activity in the 3 groups was comparable for an exogenous substrate, as judged by equal basal and EGF-stimulated phosphorylation of Val5-angiotensin II, when normalized for total EGF-binding capacity. These results suggest that fasting regulates EGF receptor kinase activity primarily by regulation of the number of hepatic EGF receptors. The possibility exists that some in vivo effects of fasting may be mediated by a reduction in EGF receptor levels.

Animals↗

Immunosuppressive treatment policies. A) Glucocorticoids: absorption of prednisolone. I. The effect of fasting, food, and food combined with antacids.

Serum concentrations of prednisolone have been measured by radioimmunoassay in 19 healthy volunteers after ingestion of 20 mg prednisolone as four 5 mg tablets. Thirteen subjects were fasting, and 6 had taken a light breakfast. Repeat studies were performed with coadministration of antacid in the 6 non-fasting subjects. The maximum serum concentration of prednisolone was higher, (mean Cmax; fasting: 597 +/- 101 ng/ml, non-fasting: Cmax 489 +/- 56 ng/ml) and the rate of absorption more rapid in the fasting than in the non-fasting subjects (absorption t1/2 fasting: 15.7 +/- 7 minutes, non-fasting: 20 +/- 11.5 minutes). The extent of bioavailability of prednisolone and the rate of elimination were the same in both groups. In the non-fasting groups, the intake of antacid with the tablets had no significant effect on these parameters. This study shows that antacid may safely be coadministered with prednisolone tablets in non-fasting subjects without reducing the rate and extent of bioavailability of prednisolone. It is not known whether the reduction in maximum prednisolone concentration found when the tablets were taken after a meal has any clinical significance.

Absorption↗

Changes in circulating fuels, pancreatic hormones and liver glycogen concentration in fasting or suckling newborn pigs.

The effect of fasting or suckling on blood glucose, circulating fuels, pancreatic hormones and liver glycogen concentration have been measured in newborn pigs during the first 48 h of life. Blood glucose concentrations fell to hypoglycaemic values after 48 h of fasting whereas for the same period of time, suckling piglets maintain a normal blood glucose. These differences are not due to hepatic glycogen mobilization, since liver is totally depleted from its high glycogen stores 24 h after birth, both in fasting and suckling piglets. Blood lactate is present at a high concentration during the first 48 h, both in fasting and suckling piglets. In contrast, blood pyruvate concentration is lower in suckling than in fasting newborn pigs. Colostrum intake leads to an increase in blood amino acid concentrations in the suckling piglets in comparison with the fasting newborn. Plasma non-esterified fatty acid levels and blood glycerol concentrations are lower in fasting piglets than in the suckling ones. In suckling newborn pigs, circulating ketone bodies are very low despite the increase in non-esterified fatty acids levels. The decrease in plasma insulin/glucagon molar ratio at birth, is due to a decrease in plasma insulin and an increase in plasma glucagon, both in fasting and suckling piglets. Plasma insulin and glucagon concentrations are higher during suckling than during fasting. The data suggest that gluconeogenesis could be impaired, in fasting newborn pigs, by a low plasma glucagon level and/or a limiting availability of non-esterified fatty acids.

Amino Acids↗

Dehydration during fasting increases serum lipids and lipoproteins.

The study was an open, prospective, randomized cross-over design to determine if dehydration during fasting increases lipid concentrations. Fifteen healthy subjects participated, 1 of whom did not complete the study. The subjects fasted once with no fluid replacement and once with salt and water supplementation. Following both fasts, blood was drawn for lipid assessments. Compared to fasting with fluid and salt replacement, fasting with no fluids was associated with higher (mean, 95% confidence interval) total serum cholesterol (8.1%, 4.3-11.9%), HDL cholesterol (7.5%, 1.8-13.1%), LDL cholesterol (10.5%, 2.2-18.8%), apolipoprotein A-1 (8.9%, 5.0-12.8%), and apolipoprotein B (10.5%, 5.2-15.8%). The change in serum triglycerides was not statistically significant (12.4%,-0.5-25.3%). There was a greater reduction in body weight during fasting with fluid restriction compared to fasting with salt and water supplementation (1.8%, 1.3-2.2%). Fasting with fluid restriction results in significantly higher lipid levels and, therefore, variation in hydration of patients could contribute to fluctuation in lipid levels of patients. Care should be taken to ensure that patients are in a standard state of hydration during assessment of lipid levels. We recommend: 1) that patients fast no longer than 12 h, and 2) that, during fasting, patients avoid unnecessary physical activity, avoid hot dry environments, ensure a liberal intake of water, and avoid diuretic substances such as caffeine.

Adult↗