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PubMed1997

Prolongation and enhancement of postischemic c-fos expression after fasting.

BACKGROUND AND PURPOSE: A rapid but transient expression of c-fos after cerebral ischemia has been extensively documented. However, the mechanism of this induction and whether induction of c-fos is neuroprotective or detrimental to the brain after ischemia is presently not clear. Fasting before transient cerebral ischemia has been shown to reduce delayed neuronal necrosis and infarct volume. The purpose of the present study was to examine the effect of preischemic fasting for 24 hours on the expression of c-fos after transient focal cerebral ischemia. METHODS: Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery and both common carotid arteries for 60 minutes. Male Long-Evans rats weighting 250 to 300 g were randomly divided into two groups: fed (control group) and food deprived for 24 hours (fasted group) before ischemic surgery. Infarct volumes were measured on the basis of triphenyltetrazolium chloride-delineated infarct areas, and plasma glucose levels were determined by the glucose oxidase method. Temporal and spatial expression of c-fos was assessed by Northern blot analysis, in situ hybridization, and immunohistochemistry. RESULTS: Fasting for 24 hours before 60 minutes of ischemia resulted in a 26.6% decrease in preischemic plasma glucose levels and a 74.5% reduction in infarct volumes in the fasted group compared with the control group. A rapid but transient induction of c-fos mRNA was observed in the ischemic cortex in control animals after 60 minutes of ischemia. Fasting not only prolonged but also enhanced the intensity of c-fos expression in the ischemic cortex. Regional c-fos expression was also different between these two groups. CONCLUSIONS: The results support the contention that c-fos expression may be compatible with its purported neuroprotective role in selected experimental paradigms. The signaling mechanisms underlying the effect of fasting and subsequent lowering of plasma glucose levels on postischemic c-fos expression remain to be explored.

Animals↗
PubMed1969

Carbohydrate metabolism in pregnancy. VI. Plasma fuels, insulin, liver composition, gluconeogenesis, and nitrogen metabolism during late gestation in the fed and fasted rat.

The effects of late pregnancy on metabolic fuels, liver composition, gluconeogenesis, and nitrogen metabolism have been examined in fed and fasted rats. Plasma free fatty acid (FFA) and immunoreactive insulin (IRI) are greater and glucose and ketones are lower in fed 19-day pregnant than they are in agematched virgin rats. A 48 hr fast elicits greater increases in FFA and ketones and more profound reductions in glucose in the pregnant rats and obliterates the differences in IRI. Fetal weight is not modified by such fasting but maternal weight losses exceed that of the nongravid rats. Livers from rats 19 days pregnant contain more and larger hepatocytes. Per mumole hepatic deoxyribonucleic acid (DNA)-phosphorus, water and protein are more abundant, whereas glycogen is unaffected. Livers from fed pregnant rats contain more lipid phosphorus and less neutral lipid fatty acid. After a 48 hr fast, hepatic steatosis supervenes in gravid animals due to accumulated neutral fat. The contents of hepatic acetyl-coenzyme A (CoA) and citric acid are not different in fed pregnant and virgin rats but are greater in the pregnant rats after fasting. Formation of glucose-(14)C and glycogen-(14)C from administered pyruvate-(14)C are the same in fed pregnant and virgin rats, but greater in the pregnant ones after a 24 or 48 hr fast. Pregnancy does not affect creatinine excretion, and urinary urea is not different in fed pregnant, virgin, and postpartum animals. Contrariwise, more nitrogen, potassium, and phosphorus are excreted by the pregnant animals during a 2 day fast. The increment in urinary nitrogen is due largely to urea on the 1st day, whereas heightened ammonia accounts for half the increase on the 2nd and correlates with the enhanced ketonuria. Muscle catabolism, gluconeogenesis, and diversion to fat are activated more rapidly and to a greater degree when food is withheld during late gestation in the rat. These catabolic propensities are restrained in the fed state. The capacity for "accelerated starvation" may confer survival benefit upon an intermittently eating mother in the presence of a continuously feeding fetus.

Animals↗
PubMed1978

Mechanisms of fasting-induced increase in insulin binding to rat adipocytes.

UNLABELLED: Fasting leads to an increase in the ability of adipocytes to bind insulin, and this was accounted for by an increase in the affinity of the receptors for insulin without any change in the number of receptors per cell. Binding affinity can increase because of a decrease in the dissociation rate constant (k(d)), an increase in the association rate constant (k(a)), or both. Kinetic studies demonstrated that fasting leads to a striking decrease in the rate at which insulin dissociates from its receptor, and the near two-fold prolongation of the time at which 50% of the bound (125)I-insulin dissociates (28+/-4 vs. 50+/-5 min) correlated quite well with the two-fold increase in binding affinity. On the other hand, the rate at which insulin associates with its receptor was essentially unchanged. Negatively cooperative interactions between receptors were readily demonstrated in cells from control and fasting animals, and the magnitude and sensitivity of this effect was the same in both groups of cells. It seemed likely that during fasting a change in the concentration of some substrate or hormone could lead to these effects on insulin binding. However, in vitro attempts to recreate the substrate and hormonal changes which occur in fasting produced no evidence to support this idea. IN CONCLUSION: (a) fasting leads to an increase in the ability of adipocytes to bind insulin because of an increase in binding affinity; (b) this increase in the affinity of the receptor for insulin was primarily accounted for by a decrease in the rate at which insulin dissociates from its receptors; and (c) fasting did not appreciably alter the negatively cooperative interactions displayed by adipocyte insulin receptors.

Adipose Tissue↗
PubMed1980

Impaired suppression of sympathetic activity during fasting in the gold thioglucose-treated mouse.

Sympathetic activity in rats and mice is diminished by fasting and increased by sucrose feeding. The central neural mechanisms coordinating changes in the functional state of sympathetic nerves with changes in dietary intake are unknown, but a role for neurons in the ventromedial hypothalamus (VMH) is suggested by the existence of sympathetic connections within the VMH and the importance of this region in the regulation of feeding behavior. To investigate the potential role of the VMH in dietary regulation of sympathetic activity [(3)H]norepinephrine turnover was measured in the hearts of fasted and sucrose-fed mice after treatment with gold thioglucose (AuTG). In control mice, norepinephrine (NE) turnover was 1.60+/-0.92 ng NE/heart per h (95% confidence limits) after 1 d of fasting and 4.58+/-0.98 after 3 d of sucrose feeding, although, in AuTG-treated mice, cardiac NE turnover in fasting was 5.45+/-1.56 and with sucrose feeding, 5.44+/-0.76. Experiments with ganglionic blockade indicate that the absence of dietary effect on NE turnover in AuTG-treated mice reflects a corresponding lack of change in central sympathetic outflow. AuTG administration, therefore, disrupts dietary regulation of sympathetic activity by abolishing the suppression of sympathetic activity that occurs with fasting. This effect of AuTG is unrelated to duration of fasting (up to 3 d) and is specific for AuTG because neither treatment with another gold thio compound (gold thiomalate) nor the presence of genetic obesity (ob/ob) prevented fasting suppression of sympathetic activity. Moreover, AuTG treatment did not impair sympathetic activation by cold exposure (4 degrees C) nor adrenal medullary stimulation by 2-deoxy-d-glucose. Thus, AuTG treatment selectively impairs dietary regulation of sympathetic activity, possibly by destruction of neurons in the VMH.

Adrenal Glands↗
PubMed1982

Differing uptake of emulsion triglyceride by the fed and fasted rat liver.

The recycling perfusion of a fasted rat liver with an apoprotein E-enriched synthetic triglyceride emulsion revealed a significantly greater hepatic uptake of both the apoprotein and the triglyceride than did the liver of a chow-fed animal. This greater hepatic triglyceride uptake by the perfused fasted liver in comparison to the fed was also noted for emulsions containing no added apoprotein or supplemented with both the E and CIII-1 proteins. However, no difference in the uptake of the triglyceride emulsion was seen for the fed and fasted livers when evaluated by a nonrecycling single pass perfusion. The isolated hepatocyte plasma membranes from fasted rats failed to demonstrate enhanced binding of apoprotein or lipid when compared to those from fed animals. If the residual E loaded triglyceride emulsion was recovered from the recycling perfusates of fed and fasted livers and evaluated in a non-recycling single-pass system, the emulsion from the fasted perfusion was cleared as facilely as previously, whereas that from the fed was less actively cleared. The emulsions retrieved from the perfusion of the fed liver contained significantly more protein than did the fasted; in particular apo C. This apparent alteration of emulsion apoproteins by the fed liver possibly results in a less active hepatic retrieval and may be important in downregulating the entry of lipoprotein triglyceride in the postabsorptive liver.

Animals↗
PubMed2005

Endocrinologic adaptations to wintertime fasting in the male American mink (Mustela vison).

The aim of this study was to investigate the endocrine response to wintertime starvation in the male American mink (Mustela vison) fasted for 16 hrs, 2 days, 3 days, 5 days, or 7 days (n =10 per group). After 2 days of fasting, the plasma leptin concentrations decreased, along with the triiodothyronine, testosterone, and progesterone levels, and the blood monocyte counts. Leptin also seems to trigger the response to fasting in mustelids by inducing immunosuppression and downregulation of the reproductive and thyroid axes. The dramatic increase in the peptide YY concentrations after 3 days of fasting may be required to suppress gastrointestinal processes during food scarcity. The plasma insulin levels decreased, and those of glucagon increased after 5 days of fasting in association with efficient glucose sparing and lipid mobilization. Body energy stores cannot be wasted for growth during nutritional scarcity and, thus, the growth hormone levels of the minks decreased after 5 days of fasting. The plasma noradrenaline and cortisol concentrations also decreased after 3 and 7 days without food, respectively. The plasma ghrelin, adiponectin, resistin, thyroxine, adrenaline, or estradiol levels did not respond to fasting. The endocrine response to food deprivation is remarkably similar in divergent mammalian orders, indicating that the hormonal signals enhancing survival during nutritional scarcity must be evolutionarily old and well conserved.

Adaptation, Physiological↗
PubMed2006

A study of association between common variation in the growth hormone-chorionic somatomammotropin hormone gene cluster and adult fasting insulin in a UK Caucasian population.

BACKGROUND: Reduced growth during infancy is associated with adult insulin resistance. In a UK Caucasian cohort, the CSH1.01 microsatellite polymorphism in the growth hormone-chorionic somatomammotropin hormone gene cluster was recently associated with increases in adult fasting insulin of approximately 23 pmol/l for TT homozygote males compared to D1D1 or D2D2 homozygotes (P = 0.001 and 0.009; n = 206 and 92, respectively), but not for females. TT males additionally had a 547-g lower weight at 1 year (n = 270; P = 0.008) than D2D2 males. We sought to replicate these data in healthy UK Caucasian subjects. We genotyped 1396 subjects (fathers, mothers and children) from a consecutive birth study for the CSH1.01 marker and analysed genotypes for association with 1-year weight in boys and fasting insulin in fathers. RESULTS: We found no evidence for association of CSH1.01 genotype with adult male fasting insulin concentrations (TT/D1D1 P = 0.38; TT/D2D2 P = 0.18) or weight at 1 year in boys (TT/D1D1 P = 0.76; TT/D2D2 P = 0.85). For fasting insulin, our data can exclude the previously observed effect sizes as the 95 % confidence intervals for the differences observed in our study exclude increases in fasting insulin of 9.0 and 12.6 pmol/l for TT relative to D1D1 and D2D2 homozygotes, respectively. Whilst we have fewer data on boys' 1-year weight than the original study, our data can exclude a reduction in 1-year weight greater than 557 g for TT relative to D2D2 homozygotes. CONCLUSION: We have not found association of the CSH1.01 genotype with fasting insulin or weight at 1 year. We conclude that the original study is likely to have over-estimated the effect size for fasting insulin, or that the difference in results reflects the younger age of subjects in this study relative to those in the previous study.

Adult↗
PubMed2004

Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice.

Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with hepatic insulin resistance. The purpose of the present study was to document the effects of 16 h of fasting in wild-type mice on insulin sensitivity in liver and skeletal muscle in relation to 1) tissue accumulation of triglycerides (TGs) and 2) changes in mRNA expression of metabolically relevant genes. Sixteen hours of fasting did not show an effect on hepatic insulin sensitivity in terms of glucose production in the presence of increased hepatic TG content. In muscle, however, fasting resulted in increased insulin sensitivity, with increased muscle glucose uptake without changes in muscle TG content. In liver, fasting resulted in increased mRNA expression of genes promoting gluconeogenesis and TG synthesis but in decreased mRNA expression of genes involved in glycogenolysis and fatty acid synthesis. In muscle, increased mRNA expression of genes promoting glucose uptake, as well as lipogenesis and beta-oxidation, was found. In conclusion, 16 h of fasting does not induce hepatic insulin resistance, although it causes liver steatosis, whereas muscle insulin sensitivity increases without changes in muscle TG content. Therefore, fasting induces differential changes in tissue-specific insulin sensitivity, and liver and muscle TG contents are unlikely to be involved in these changes.

Animals↗
PubMed1984

The 2-deoxyglucose test as a supplement to fasting for detection of childhood hypoglycemia.

The acute response to simulated hypoglycemia induced by 2-deoxyglucose (2DG) was compared with the prolonged fasting test as a possible screening test for detection of childhood hypoglycemia. Ten children, ages 2-9 yr, without a documented history of hypoglycemia were classified retrospectively as reference subjects. While fasting, their plasma glucose decreased to an average of 50 mg/dl (range, 30-74) between 28-36 h. After infusion of 2DG, 50 mg/kg IV over 30 min, their plasma glucose increased by an average of 35 mg/dl (range, 19-56) between 60-120 min. The half-life of plasma 2DG was 48 min. Twenty-three other children in the same age range had an abnormal response to one or both of these tests. Thirteen of these children became definitely hypoglycemic while fasting (glucose less than 30 mg/dl) and also failed to increase their plasma glucose by more than 10 mg/dl after 2DG. Five children had plasma glucose values between 30-40 mg/dl during the first 24 h of fasting that were associated with a change in mental status but responded to 2DG with an increase in plasma glucose. The remaining five subjects had an apparently normal response to fasting but did not respond to 2DG; two of these had documented spontaneous hypoglycemia. No cases of documented hypoglycemia were undetected by either test. It is concluded that the 2DG test is a short safe supplement to fasting which is equally effective as the prolonged fasting test in detecting hypoglycemia. Neither test alone is completely reliable, but the combination is complementary.

Blood Glucose↗
PubMed1984

The 2-deoxyglucose test as a supplement to fasting for detection of childhood hypoglycemia.

The acute response to simulated hypoglycemia induced by 2-deoxyglucose (2DG) was compared with the prolonged fasting test as a possible screening test for detection of childhood hypoglycemia. Ten children, ages 2-9 yr, without a documented history of hypoglycemia were classified retrospectively as reference subjects. While fasting, their plasma glucose decreased to an average of 50 mg/dl (range, 30-74) between 28-36 h. After infusion of 2DG, 50 mg/kg IV over 30 min, their plasma glucose increased by an average of 35 mg/dl (range, 19-56) between 60-120 min. The half-life of plasma 2DG was 48 min. Twenty-three other children in the same age range had an abnormal response to one or both of these tests. Thirteen of these children became definitely hypoglycemic while fasting (glucose less than 30 mg/dl) and also failed to increase their plasma glucose by more than 10 mg/dl after 2DG. Five children had plasma glucose values between 30-40 mg/dl during the first 24 h of fasting that were associated with a change in mental status but responded to 2DG with an increase in plasma glucose. The remaining five subjects had an apparently normal response to fasting but did not respond to 2DG; two of these had documented spontaneous hypoglycemia. No cases of documented hypoglycemia were undetected by either test. It is concluded that the 2DG test is a short safe supplement to fasting which is equally effective as the prolonged fasting test in detecting hypoglycemia. Neither test alone is completely reliable, but the combination is complementary.

Adolescent↗
PubMed1992

Effect of insulin-induced and fasting hypoglycemia on perinatal hypoxic-ischemic brain damage.

Experiments in adult animals have indicated that hyperglycemia accentuates whereas hypoglycemia ameliorates hypoxic-ischemic brain damage. To determine whether hypoglycemia is protective or deleterious to the perinatal brain subjected to hypoxia-ischemia, 7-d postnatal rats were rendered hypoglycemic either by receiving an s.c. injection of insulin or fasting for 12 h. All rat pups underwent unilateral common carotid artery ligation followed by exposure to 8% oxygen-balance nitrogen at 37 degrees C for 2 h. Control animals (no insulin or fasting) received s.c. injections of normal saline. Mean blood glucose concentrations were 5.4 +/- 0.1, 4.3 +/- 0.2, and 3.4 +/- 0.1 mmol/L for control, insulin, and fasted animals, respectively. Blood beta-hydroxybutyrate concentrations were identical (0.5 +/- 0.1 mmol/L) for control and insulin-treated animals, but more than doubled in concentration in the fasted animals (p less than 0.001). Mortality rates during hypoxia-ischemia were higher in the insulin-treated animals (30%) than in either the fasted (4%) or control (0%) animals (p less than 0.05). Fasted animals showed a significant reduction in hypoxic-ischemic brain damage as compared with either the insulin-treated or control animals. Insulin-treated animals were not significantly different from controls. The findings indicate that 1) insulin induced hypoglycemia does not provide a protective effect on perinatal hypoxic-ischemic brain damage, as in adults; and 2) fasting adequate to produce hypoglycemia and ketonemia improved neuropathologic outcome.

Animals↗
PubMed1999

Colon cancer is induced by a single low dose of azoxymethane in fasted-refed rats.

We reported previously that fasting-refeeding enhanced the growth of preneoplastic lesions in the colon of rats induced by 20 mg/kg of azoxymethane (AOM). Here we studied whether fasting-refeeding could also affect 1) the induction of colon cancer by the same dose of AOM and 2) the induction of foci by lower doses of AOM that do not induce foci in fully fed rats. Fully fed and fasted-refed rats were given AOM by single subcutaneous injection, and the development of foci or tumors was evaluated three months or one year later. The results of the long-term carcinogenesis experiments showed that the total incidence of tumors was increased in the fasted-refed rats. Moreover, although fully fed rats developed foci only when injected with 7.5, 10, or 20 mg/kg of the carcinogen, a significant number of foci were also induced by 5 mg/kg in fasted-refed rats. The crypt multiplicity of foci was also higher when rats were exposed to fasting-refeeding, even when the number of foci was unchanged. These data suggest that growth perturbations induced by fasting-refeeding lead to the development of preneoplastic lesions with doses of AOM too low to trigger foci in fully fed rats and produce enhanced sensitivity to the development of intestinal tumors.

Animals↗
PubMed2004

Impaired leptin expression and abnormal response to fasting in corticotropin-releasing hormone-deficient mice.

Leptin has been postulated to comprise part of an adipostat, whereby during states of excessive energy storage, elevated levels of the hormone prevent further weight gain by inhibiting appetite. A physiological role for leptin in this regard remains unclear because the presence of excessive food, and therefore the need to restrain overeating under natural conditions, is doubtful. We have previously shown that CRH-deficient (Crh(-/-)) mice have glucocorticoid insufficiency and lack the fasting-induced increase in glucocorticoid, a hormone important in stimulating leptin synthesis and secretion. We hypothesized that these mice might have low circulating leptin. Indeed, Crh(-/-) mice exhibited no diurnal variation of leptin, whereas normal littermates showed a clear rhythm, and their leptin levels were lower than their counterparts. A continuous peripheral CRH infusion to Crh(-/-) mice not only restored corticosterone levels, but it also increased leptin expression to normal. Surprisingly, 36 h of fasting elevated leptin levels in Crh(-/-) mice, rather than falling as in normal mice. This abnormal leptin change during fasting in Crh(-/-) mice was corrected by corticosterone replacement. Furthermore, Crh(-/-) mice lost less body weight during 24 h of fasting and ate less food during refeeding than normal littermates. Taken together, we conclude that glucocorticoid insufficiency in Crh(-/-) mice results in impaired leptin production as well as an abnormal increase in leptin during fasting, and propose that the fast-induced physiological reduction in leptin may play an important role to stimulate food intake during the recovery from fasting.

Adrenocorticotropic Hormone↗
PubMed1977

Diminished ketosis and triglyceridemia during fasting in odd-carbon enriched pregnant rats.

The lipolysis, ketosis and hypertriglyceridemia of fasted rats in late pregnancy may be related to decreased insulin secretion geared to decreased glucose availability. In odd-carbon fatty acid enriched (OCE) rats, the odd-carbon fatty acids (OCFA) mobilized during fasting provide terminal three-carbon residues which are glucogenic, thereby permitting blood glucose and insulin to be maintained close to fed levels. The present study has used OCE rats to evaluate the role of insulin in the altered fat metabolism of the fasted rats in late pregnancy. The adipose tissue of 24 female Sprague-Dawley rats was enriched to more than 25% undecanoate (c11:0) and higher OCFA by feeding them a complete diet high in triundecanoin content for six weeks. Twenty-four female controls were fed a similar diet except that the fat was exclusively corn oil. Both OCE and control rats were than mated and on day 18 of pregnancy were divided into four groups: one group was killed fed, one after a 24 h fast, and one after a 48 h fast; the fourth group was fed to day 20 of pregnancy and then killed. In the fed state, the concentrations of glucose, ketones, and cholesterol in serum, as well as that of glycogen in liver, were the same in control and OCE rats. Insulin and triglycerides were similarly elevated in the two groups. After two days of fasting, serum glucose, insulin, and liver glycogen concentrations were significantly higher in OCE than in control rats, while ketones and triglycerides were significantly lower. No significant changes occurred in serum cholesterol. The results are consistent with a predominantly insulin effect in the pregnant OCE rats in diminsihing the marked fasting lipolysis, hyperketonemia and hypertriglyceridemia observed in controls, but do not rule out inhibition of FFA release by in situ re-esterification to glycerol derived from glucose or propionic acid.

Acidosis↗
PubMed1981

The influence of fasting and the thyroid state on the activity of thyroxine 5'-monodeiodinase in rat liver: a kinetic analysis of microsomal formation of triiodothyronine from thyroxine.

In the present studies, we have evaluated the effects of fasting, variations in thyroid state, and interactions thereof on the kinetic properties of the microsomal enzyme in rat liver that generates T3 from T4. The formation of T3 and T4 (T3-neogenesis) in preparations of rat liver microsomes enriched with 10 mM dithiothreitol was monitored by assessing the formation of [125I]T3 from [125I]T4 in the presence of various concentrations of stable T4. T3-neogenesis in this system was a saturable process that obeyed the laws of first order enzyme kinetics. The effects of diverse in vivo manipulations on the kinetics of T3-neogenesis were assessed. The Vmax was markedly decreased in preparations from thyroidectomized animals, being, respectively, partially and completely restored to normal with daily maintenance therapy with T4, (0.5 and 1.5 microgram/100 g BW) and markedly increased after the administration of supraphysiological replacement doses of T4 (5.0 microgram/100 g . day). Km was not affected by alterations in thyroid state. In experiments concerning the effects of fasting, cognizance was taken of the fact that hypothyroidism regularly evolves as a consequence of fasting. The Vmax was decreased markedly, and Km was slightly decreased in preparations from intact rats fasted 72 h but not given physiological replacement with T4 or T3. In contrast, Vmax and Km were unchanged in hepatic microsomes from intact rats fasted 72 h but given daily parenteral replacement with T4 (1.5 microgram/100 g) or T3 (0.5 microgram/100 g). These data demonstrate that hypothyroidism resulting from either thyroidectomy or fasting produces decreased intrinsic activity of the microsomal T4 5'-monodeiodinase. In contrast, fasting without concurrent hypothyroidism does not influence the intrinsic activity of the hepatic T3-neogenetic enzyme. (Endocrinology 108: 472, 1981)

Animals↗
PubMed1983

The role of insulin and glucocorticoids in the regulation of hepatic glycogen metabolism: effect of fasting, refeeding, and adrenalectomy.

The roles of insulin, adrenal corticol hormones, and nutritional factors in the regulation of hepatic glycogen metabolism were investigated by means of fasting and refeeding normal and adrenalectomized (ADX) rats. More specifically, the hypothesis in question in this study is that certain hepatic phosphoprotein phosphatases are targets of insulin action in liver. In anesthetized rats, the hepatic glycogen concentration and the activities of hepatic glycogen synthase, glycogen synthase phosphatase, glycogen phosphorylase, and phosphorylase phosphatase were correlated with peripheral plasma glucose and immunoreactive insulin levels. Hepatic phosphatase activities were measured in (soluble) the high speed supernatant and smooth endoplasmic reticulum (SER). Fasting resulted in expected diminutions in circulating glucose and insulin levels and loss of hepatic glycogen. These changes were greater in ADX rats. The percentage of hepatic glycogen synthase in the active or I form increased with fasting in normal rats, but did not change in ADX rats. Hepatic synthase phosphatase activities were decreased in SER by fasting in both normal and ADX rats, but to a much greater extent in the latter; soluble synthase phosphatase was much less affected by fasting. The percentage of phosphorylase in the active or a form was significantly decreased in normal, but not ADX, rats. Phosphorylase phosphatase activities were not significantly changed by fasting in any of the subcellular fractions in normal liver, but were increased in the hepatic SER of ADX rats. Refeeding fasted rats for 2 and 6 h resulted in increased hepatic glycogen, activation of glycogen synthase, and increased circulating levels of both insulin and glucose. Refeeding also caused increases in SER-associated synthase phosphatase activity in ADX animals. SER phosphorylase phosphatase activities were significantly increased by refeeding in normal rats, but were decreased in ADX rats. Regression analysis of the data suggested statistically significant positive correlations between insulin levels and SER synthase phosphatase activity in ADX animals, on the one hand, and SER synthase phosphatase and the percentage of synthase in the I form, on the other. No statistically significant correlation between insulin levels and phosphorylase phosphatase activities could be demonstrated. These results are compatible with the hypothesis that glycogen synthase phosphatase activity in liver, especially that associated with SER, is subject to physiological regulation by circulating levels of insulin. In contrast, phosphorylase phosphatase activity seems to be much less influenced by changes in the circulating insulin level. The results are compatible with the proposition that SER-associated phosphoprotein phosphatases are physiologically relevant in the regulation of hepatic glycogen metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1976

Nutrition and somatomedin. I. Effect of fasting and refeeding on serum somatomedin activity and cartilage growth activity in rats.

The relationship between nutrition, somatomedin, and growth was studied in young male rats which were fasted for 72 h, and then refed. Cartilage growth activity was measured by the incorporation of SO4 by costal cartilage incubated in vitro. Serum somatomedin activity was measured by the ability of sera to stimulate the incorporation of SO4 in vitro by cartilage from hypophysectomized rats or normal young pigs. Cartilage growth activity was unchanged after 24 h of fasting, but decreased significantly to hypopituitary levels after 72 h. The decrease in cartilage growth activity could not be attributed to a decrease in the ability of cartilage to respond to somatomedin, since fasted rat cartilage incubated in vitro had significantly greater stimulation from the addition of normal rat serum (normal somatomedin) than from the addition of hypophysectomized rat serum (low somatomedin). A decrease in serum somatomedin preceded the decrease in growth activity; somatomedin was significantly decreased after 24 h of fasting, and fell to hypopituitary levels after 72 h of fasting. The decrease in somatomedin could not be attributed to growth hormone deficiency, since treatment with bGH did not prevent the fall in somatomedin. The direct addition of fasted rat serum to normal rat serum did not inhibit the somatomedin activity of the normal serum. The refeeding of 72h-fasted rats was associated with an increase in serum somatomedin which was significant after 6 h, and comparable to control levels after 24 h of refeeding. The increase in somatomedin was followed by an increase in cartilage growth activity, which was significant after 12 h, and comparable to control levels after 48 h of refeeding. We conclude that adequate food intake appears to be required for the maintenance of normal levels of somatomedin; the processing of nutrients may modulate the generation of somatomedin.

Animal Nutritional Physiological Phenomena↗
PubMed1994

Reduced levels of messenger ribonucleic acid for calcium channel, glucose transporter-2, and glucokinase are associated with alterations in insulin secretion in fasted rats.

Expression of the genes for voltage-dependent calcium channels (VDCCs), glucose transporter-2 (GLUT2), and glucokinase was studied in pancreatic islets obtained from normal rats after periods of fasting and refeeding using a competitive polymerase chain reaction procedure. A 72-h fast induced about a 3-fold decrease in the beta-cell/neuroendocrine type VDCC alpha 1-subunit and GLUT2 messenger RNA (mRNA) levels and about a 2-fold decrease in insulin and glucokinase mRNA levels compared to those in fed and refed rats. No significant differences were found in beta-actin and the cardiac-type VDCC alpha 1-subunit mRNA levels among fed, fasted, anf refed rats. We also studied insulin secretion from the isolated perfused pancreata obtained from these animals. We found an elevated threshold and decreased insulin release in response to a stepwise increase in glucose concentrations in the isolated perfused pancreata obtained from fasted rats. Fasting also resulted in a dramatic decrease in insulin secretory responses during the application of an L-type VDCC agonist, Bay K8644 (1 microM). Furthermore, fasting resulted in a significant decrease in both 45Ca2+ uptake by the isolated islets and insulin release from the islets. A strong positive correlation was observed between glucose-induced 45Ca2+ uptake and insulin output among the animals studied. On the other hand, after a 24-h refeeding, significant increases in the insulin secretory response to glucose and Bay K8644 were found, with a normalization in mRNA levels for these components. It, thus, appears that the alterations in beta-cell sensitivity to glucose that occur with fasting and refeeding are the result of complex metabolic alterations in the islet associated with reductions in expression of at least in part the beta-cell/neuroendocrine type VDCC in addition to two components of the glucose-sensing apparatus, including glucokinase and GLUT2, and the reduction in mRNA for insulin.

Animals↗