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PubMed2005

Hormonal and metabolic adaptation to fasting: effects on the hypothalamic-pituitary-ovarian axis and reproductive performance of rabbit does.

To assess the impact of acute caloric shortage on reproduction, rabbit does were either fed ad libitum (control, AL), or fasted for 24 (STF) or 48 h (LTF) before induction of ovulation with GnRH injection. Blood samples were collected during the last 3 h of fasting, and the following 4 h after GnRH injection, when feed was provided again, to measure plasma concentrations of LH, estradiol-17beta, leptin, insulin, T3, corticosterone, glucose, and NEFA. Before re-feeding, plasma leptin, insulin, and T3 concentrations were lower (P < or = 0.01) in both fasted groups than in controls, but then gradually increased following realimentation to match those of controls. During fasting, corticosterone levels were higher (P < or = 0.01) in LTF than in STF and AL does, but decreased to control values soon after realimentation. During fasting, plasma glucose concentrations did not differ among groups, but upon re-feeding they markedly increased (P < or= 0.01) both in STF and LTF does. NEFA levels were also more elevated (P < or = 0.01) in fasted rabbits than in controls, and rapidly decreased (P < or = 0.01) after re-feeding. Following GnRH injection, LH peak was lower (P < or = 0.01) in LTF than in AL and STF does. Estradiol-17beta showed higher pulse frequency and amplitude in AL than in STF and LTF does. Compared to controls, receptivity rate of STF and LTF artificially inseminated does declined respectively by -20.5% (P < or = 0.05) and -22.7%, and fertility rate by -23.9% (P < or = 0.05) and 21.4%, but no difference was found in ovulation rate. In summary, nutritional status of does, as modified by fasting, greatly influenced fertility, metabolic and reproductive hormones.

Animals↗
PubMed2006

The evaluation of antimuscarinic-induced convulsions in fasted rats after food intake.

The present study was performed to evaluate convulsions after food intake in fasted rats pretreated with scopolamine or atropine and to determine whether these convulsions respond to drugs found effective in fasted mice. Scopolamine (2.4 mg/kg) and atropine (2.4 mg/kg) were given intraperitoneally (i.p.) to rats fasted for 52h. Both drugs induced convulsions after animals were allowed to eat ad lib. Another group of fasted rats pretreated with saline, MK-801 (0.1mg/kg), clonidine (0.1mg/kg), chlorpromazine (2 and 4 mg/kg), valproate (200mg/kg), diazepam (1.5 and 2mg/kg) or gabapentin (50mg/kg) were treated i.p. with saline or scopolamine (2.4 mg/kg) and were allowed to eat ad lib. Clonidine, MK-801, chlorpromazine (4 mg/kg) and diazepam (2 mg/kg) reduced the incidence of scopolamine-induced convulsions in fasted rats. Gabapentin could only prolong the onset of convulsions. Neither treatment was effective against myoclonus of hindlimbs. Present results showed that fasted rats also develop antimuscarinic-induced convulsions which do not completely respond to treatments found effective in convulsions of fasted mice.

Animals↗
PubMed2006

Leptin levels decline steadily during prolonged fasting in lean children.

OBJECTIVE: To evaluate the effects of fasting on serum leptin levels in lean children. STUDY DESIGN: Seventeen children, age 7.7 +/- 4.3 years with mean body mass index (BMI) of 16.7 +/- 2.7 kg/m(2), underwent standard diagnostic fasts for suspected hypoglycemia. Blood was sampled at 6-hour intervals for glucose, insulin, C-peptide, leptin, free and total insulin-like growth factor-1, insulin-like growth factor-binding protein-1, growth hormone, cortisol, ketones, and free fatty acids. RESULTS: Subjects fasted 15 to 40 hours, and initial leptin levels were related to BMI and age. Leptin declined by 0.5 ng/mL per each fasting hour (P = .008), using a longitudinal mixed effects model. Leptin dropped significantly from an initial mean +/- SEM during the first 6 hours of 15.9 +/- 5.5 ng/mL to 3.5 +/- 0.9 ng/mL at the end of fasting. Mixed longitudinal effects models demonstrated that leptin was significantly related to insulin over time (P < .0001) as well as C-peptide (P < .0001). Significant relations were also seen with total insulin-like growth factor-1 over time, beta-hydroxybutyrate and insulin, and insulin-like growth factor-binding protein-1 and insulin. CONCLUSIONS: After 6 hours, leptin levels steadily decline during prolonged fasting in lean children. The decline probably is related to the suppression of insulin secretion. Although baseline leptin levels were related to BMI and age, in the final fasting sample, leptin levels showed minimal variation in this pediatric cohort encompassing a wide age range.

Body Mass Index↗
PubMed2006

Effect of fasting on voice in women.

OBJECTIVE/HYPOTHESIS: To study the effect of fasting on voice in women: abstinence from food and water intake between 14 and 18 hours. STUDY DESIGN: A prospective study on female subjects. MATERIAL AND METHOD: A total of 28 female subjects were included in this study. Their age ranged between 21 and 45 years. Subjects with vocal symptoms or vocal fold lesions were excluded. The subjects were tested when they were not fasting and while fasting after the first week of intermittent fasting during Ramadan. Each subject was first asked about her vocal symptoms and the ease of phonation or phonatory effort. Then each underwent acoustic analysis and laryngeal video-endostroboscopy. RESULTS: Vocal fatigue was the most common reported complaint (53.6%) followed by deepening of the voice (21.4%) and harshness (10.2%). Self-reported phonatory effort was significantly affected by fasting (P value < 0.001). Out of the 28 subjects, 23 had an increase in their phonatory effort. Vocal acoustic parameters did not change markedly except for the maximum phonation time, which decreased significantly. Laryngeal video-endostroboscopy did not reveal any significant changes during fasting. All stroboscopic parameters were the same except for a decrease in the amplitude of the mucosal waves in one subject and the presence of a posterior chink in three subjects. CONCLUSION: Fasting affects voice. There is an increase in the phonatory effort, and vocal fatigue is the most common symptom.

Adult↗
PubMed2004

Pinealectomy alters adipose tissue adaptability to fasting in rats.

This study investigated the effects of pinealectomy and fasting on rat adipose tissue metabolism, as well as on profiles of the hormones directly involved in its regulation (insulin, leptin, and corticosterone). Pinealectomized (PINX) and sham-operated (CONTROL) adult male Wistar rats were killed 6 weeks after surgery, in either fed or fasted (12 and 36 hours) states. Blood samples (for glucose and hormone determinations) and peri-epididymal adipocytes (for in vitro insulin-stimulated glucose uptake, oxidation, and incorporation into lipids) were collected. Pineal ablation decreased insulin-stimulated glucose uptake in adipocytes of both fed and fasted animals without affecting insulin-binding capacity. Pinealectomy attenuated the reduction in the ability to oxidize glucose in both basal and insulin-stimulated states during fasting. This alteration in the ability of adipocytes to oxidize glucose appeared together with a decrease in insulin-induced glucose incorporation into lipids in PINX animals. Additionally, pinealectomized rats showed higher corticosterone levels in both fed and fasted states, and a lower leptinemia with 36 hours of fasting, in comparison to CONTROLs. In conclusion, our data reinforce the hypothesis that the pineal gland has a role in the modulation of adipocyte metabolism, and its absence alters metabolic adaptation to fasting in rats.

Adipocytes↗
PubMed2005

Effects of a westernized lifestyle on the association between fasting serum nonesterified fatty acids and insulin secretion in Japanese men.

The effects of the prolonged elevation of nonesterified fatty acid (NEFA) levels on insulin secretion have been controversial and thought to be sex-specific. To investigate the association between a westernized lifestyle and the effects of NEFA on insulin secretion in Japanese men, we examined 67 nondiabetic Japanese-American men and 220 nondiabetic native Japanese men who underwent a 75-g oral glucose tolerance test (OGTT). Most Japanese Americans we surveyed are genetically identical to Japanese living in Japan, but their lifestyle is more westernized. Sets of multiple regression analyses were performed to evaluate the relationship between the sum of the immunoreactive insulin (IRI) levels during the OGTT ((Sigma)IRI) and clinical parameters. Japanese Americans had higher levels of fasting IRI, (Sigma)IRI, and a higher insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR]) than native Japanese, whereas there were no significant differences in fasting NEFA and triglyceride levels. A multiple regression analysis adjusted for age, fasting triglycerides, and body mass index (BMI) demonstrated that the fasting NEFA level was an independent determinant of the (Sigma)IRI only in Japanese-American men ( P = .001), but not in native Japanese men ( P = .054). Even when HOMA-IR was included in models instead of BMI, the NEFA level was a significant variable of (Sigma)IRI only in Japanese Americans ( P < .001), and not in native Japanese ( P = .098). In addition, a multiple regression analysis adjusted for age, fasting triglycerides, and BMI demonstrated that the fasting NEFA level was the only independent determinant of (Sigma)C-peptide in Japanese-American men ( P = .041). In conclusion, NEFA seems to be associated with insulin secretion independent of obesity or HOMA-IR. A westernized lifestyle may increase the effects of serum fasting NEFA levels on total insulin secretion after a glucose load in Japanese men.

Adult↗
PubMed2006

Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice.

We found reduced locomotor activity (LA) under fasting in systemic carnitine-deficient juvenile visceral steatosis (jvs(-/-)) mice. When food was withdrawn at 8:00 a.m. (lights-off at 7:00 p.m., 12h/cycle), the nocturnal LA of jvs(-/-) mice was much less than the control (jvs(+/+) and jvs(+/-)) mice. LA recovered under carnitine or sucrose administration, but not under medium-chain triglyceride. In addition, fasted jvs(-/-) mice, without any energy supply, were activated by modafinil, a stimulator of the dopamine pathway. These results suggest that the reduced LA is not adequately explained by energy deficit. As the fasted jvs(-/-) mice showed lower body core temperature (BT), we examined the central nervous system regulating LA and BT. We found lower percentage of c-Fos positive orexin neurons in the lateral hypothalamus and reduced orexin-A concentration in the cerebrospinal fluid of fasted jvs(-/-) mice. Sleep analysis revealed that fasted jvs(-/-) mice had disruption of prolonged wakefulness, with a higher frequency of brief episodes of non-REM sleep during the dark period than fasted jvs(+/+) mice. These results strongly suggest that the reduced LA in fasted jvs(-/-) mice is related to the inhibition of orexin neuronal activity.

Animals↗
PubMed2006

[11C]palmitate kinetics across the splanchnic bed in arterial, portal and hepatic venous plasma during fasting and euglycemic hyperinsulinemia.

PURPOSE: The liver is fundamental in regulating lipid metabolism, and it supplies fatty acids (FA) to the rest of the body in the form of triglycerides (TG); the time-related relevance of this process is incompletely defined. The aim of the study was to investigate the appearance of labeled TG in the hepatic vascular bed after [11C]palmitate injection during fasting and insulin stimulation. METHODS: Plasma [11C]palmitate kinetics in arterial, portal and hepatic venous lipid fractions was studied in eight anesthetized pigs during fasting or euglycemic hyperinsulinemia. Plasma analyses were conducted at 10 and 40 min after tracer injection. Corresponding liver positron emission tomography (PET) images were acquired for the semiquantitative determination of hepatic FA uptake. RESULTS: At 10 min, plasma levels of unchanged [11C]palmitate were lower in hyperinsulinemic than in fasting experiments in the artery and in the portal vein (P< or=.03), suggesting faster clearance. Levels of unmetabolized [11C]palmitate did not differ between portal and arterial plasma. In the fasting state, a tendency to a positive arterial and portal vs. hepatic venous gradient was observed, indicative of net hepatic [11C]palmitate extraction. Labeled TG were already detectable at 10 min (fasting vs. hyperinsulinemia, ns) and were higher in fasting than in hyperinsulinemic animals at 40 min (92+/-1% and 82+/-6% of arterial plasma radioactivity). Higher proportions of labeled TG were recovered in portal vein plasma, suggesting release by the gut. The portal and the arterial-portal vs. hepatic venous TG gradient tended to be positive. Accordingly, hepatic FA uptake was higher, but declined more rapidly during fasting than during hyperinsulinemia. CONCLUSION: The study indicates that the redistribution of [11C]palmitate between different lipid pools occurs within the short time interval of most PET experiments and is strongly influenced by insulin. Labeled TG constitute an additional [11C]palmitate source in the modeling of PET data.

Animals↗
PubMed2004

Fasting breath hydrogen concentration in short bowel syndrome patients with colon incontinuity before and after antibiotic therapy.

OBJECTIVE: Nutrition success in short bowel syndrome (SBS) depends on the intake nutrients and the intestinal absorption capacity. An evaluation of energy expenditure and oxidation of substrate can be obtained with indirect calorimetry by measuring O(2) and CO(2) in the respiration. Elevated colonic fermentation can occur in SBS, producing H(2) and CO(2), which can also be eliminated through respiration and as a consequence affect the results from indirect calorimetry. The objective of this study was to determine the fasting breath H(2) concentration and alterations before and after antibiotic therapy in patients with severe SBS with colon in continuity. METHODS: The study was conducted in two phases. In phase 1, the fasting breath H(2) concentrations were measured in 10 patients with severe SBS with colon incontinuity and a control group of 10 healthy volunteers. In phase 2, the fasting breath H(2) concentrations were re-evaluated after treatment for 7 d with antibiotics in six patients with high rates of H(2). The analyses were performed with a gas chromatograph (microanalyzer DP; Quintron Instruments, Milwaukee, WI, USA), with results of breath hydrogen and methane concentration expressed in parts per million (ppm). RESULTS: In phase 1, the levels of fasting breath H(2) were higher in the patients with severe SBS with colon incontinuity than in the healthy controls (32.00 +/- 17.77 versus 5.30 +/- 3.31 ppm; P < 0.001), with 7 of 10 patients presenting levels of H(2) above the normal rate (12 ppm). The presence of an ileocecal valve did not modify the results significantly. In phase 2, all six patients treated with antibiotics presented normalization in the levels of fasting breath H(2) (from 43.50 +/- 6.90 ppm to 1.33 +/- 1.03 ppm; P < 0.001) and concomitant improvement in the gastrointestinal symptoms. CONCLUSIONS: In relation to the healthy controls, patients with SBS with colon incontinuity presented higher levels of fasting breath H(2). Antibiotic therapy normalized the levels of fasting breath H(2) and improved the gastrointestinal symptoms. We suggest that the breath H(2) test may be performed routinely in patients with SBS to diagnose elevated intestinal fermentation, prevent errors in the interpretation of the indirect calorimetry, and treat eventual associated gastrointestinal symptoms.

Adult↗
PubMed2005

Perinatal MSG treatment attenuates fasting-induced bradycardia and metabolic suppression.

We studied the effect of arcuate nucleus (ARC) lesions induced pharmacologically by the perinatal treatment of monosodium l-glutamate (MSG) on the cardiovascular, metabolic, and behavioral responses to fasting. Saline and MSG-treated male Sprague-Dawley rats were instrumented with telemetry devices for measurement of mean arterial pressure (MAP) and heart rate (HR) and housed in room calorimeters at an ambient temperature (T(a)) of 23 degrees C for assessment of oxygen consumption (VO(2)). At baseline, controls and MSG-treated rats had similar MAP (control=95+/-4; MSG=91+/-2 mmHg), HR (control=323+/-4; MSG=324+/-2 bpm), and VO(2) (control=8.7+/-0.3; MSG=8.6+/-0.2 ml/min). There were no differences in fasting-induced reductions in body weight or in food intake upon refeeding. MSG-treatment significantly attenuated fasting-induced reductions in HR and VO(2). This effect was specific to reduced caloric availability, as MSG-treated rats exhibited intact capacity to both increase and decrease HR and VO(2) in response to cold (T(a)=15 degrees C) and to thermoneutrality (T(a)=30 degrees C). Additional studies were performed in saline- and MSG-treated rats chronically treated with beta(1)-adrenergic receptor blockade (atenolol) prior to and during fasting. In controls, the cardiovascular responses to fasting during beta(1)-blockade were blunted and generally mimicked the effects of MSG-treatment, while beta(1)-blockade had no additional effect on MSG-treated rats. The results are consistent with the hypothesis that ARC neuronal signaling is requisite for intact homeostatic responses to fasting and may participate in fasting-induced withdrawal of cardiac sympathetic activity.

Animals↗
PubMed2006

Fasting duration influences the inhibition of food intake by histamine in chickens.

This work was performed to investigate the effect of duration of fasting in the responses of chickens peripherally injected with histamine on the regulation of food intake. The animals were 16-week-old male chickens from layer-strain and the doses of histamine used were 500 and 1000 microg/kg of body weight. The non fasted chickens showed no effect of histamine on the food intake. When the animals were fasted during 4 h, injected with the histamine and immediately refed, the results showed a reduction of food intake only the first 15 min of the experiments with the dose of 1000 mug. In chickens fasted during 16 h or 26 h and refed, the histamine inhibited significantly the food intake at all time with the two doses. When the animals were fasted 16 h and refed during 60 min before the administration of the histamine, there is no inhibition of food intake. No effect on water intake has been registered in all the experiments. The blockade of the action of histamine injected in chickens fasted during 16 h by cimetidine and promethazine, show that the inhibition of food intake occurs through the H1 but not through H2 receptors. The fasting used in paradigm to investigate the effect of drugs such as histamine on the appetite, can affect differently the responses according to its duration, as observed here in chickens.

Animals↗
PubMed2002

Contribution of abdominal obesity and hypertriglyceridemia to impaired fasting glucose and coronary artery disease.

Multiple logistic regression models were used in a cross-sectional study to determine the relation of fasting glycemia to angiographically assessed coronary artery disease (CAD) in 569 men (aged 18 to 69 years) who were stratified according to fasting blood glucose concentrations (<6.1 mmol/L, and 6.1 to 6.9 mmol/L or 110 to 124 mg/dl), waist circumference (<90 vs >or=90 cm), and fasting triglyceridemia (<2.0 vs >or=2.0 mmol/L or <177 vs >or=177 mg/dl). For this purpose, nondiabetic impaired fasting glucose was defined as from 6.1 to 6.9 mmol/L (110 to 124 mg/dl) compared with 250 normoglycemic controls (fasting glycemia <6.1 mmol/L or <124 mg/dl) without history of CAD. In the absence of "hypertriglyceridemic waist," impaired fasting glucose was not predictive of CAD. However, the risk of CAD was markedly higher among subjects characterized by both the hypertriglyceridemic waist phenotype and the presence of impaired fasting glucose (odds ratio 8.5, 95% confidence intervals 3.5 to 20.4; p <0.05) compared with the normoglycemic group with low waist circumferences and triglyceride levels. Thus, the results of the present study emphasizes the importance of other underlying metabolic abnormalities, such as abdominal obesity and related atherogenic dyslipidemia, in the modulation of the CAD risk associated with hyperglycemia.

Abdomen↗
PubMed1999

Effects of leptin on fasting-induced inhibition of neuronal nitric oxide synthase mRNA in the paraventricular and supraoptic nuclei of rats.

Fasting induced a reduction in neuronal nitric oxide synthase (nNOS) mRNA in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of rats. The effect of intracerebroventricular (i.c.v.) administration of leptin on the nNOS mRNA level in the PVN and SON of fasting rats was studied by in situ hybridization histochemistry. Leptin (10 microg/kg b.wt) or vehicle was administered i.c.v. at 1700 h on two successive days fasting for 2 days. Fasting for 2 days with i.c.v. administration of vehicle induced a significant reduction of nNOS mRNA in the PVN and SON. Central administration of leptin prevented the fasting-induced reduction of nNOS mRNA in the PVN and SON. Administration of leptin also prevented the fasting-induced reductions of thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH) mRNAs in the parvocellular division of the PVN. These results suggest that leptin is associated with fasting-induced reduction of nNOS mRNA in the PVN and SON as well as TRH and CRH mRNAs in the PVN.

Animals↗
PubMed1997

Pituitary neuromedin B content in experimental fasting and diabetes mellitus and correlation with thyrotropin secretion.

Fasting and diabetes mellitus in the rat model have been associated with abnormalities of thyrotropin (TSH) secretion. Neuromedin B is a bombesin-like peptide highly concentrated in the pituitary gland that has been shown to have inhibitory action on TSH secretion, acting as an autocrine/paracrine factor. Here, we aimed to determine if the pituitary content of neuromedin B would change in fasted rats (1, 2, 3, and 4 days of food deprivation) and streptozotocin (55 mg/kg body weight)-diabetic rats. The total pituitary content of neuromedin B was decreased in fasted rats, except at 2 days of fasting, as was the total protein content in the gland; however, the concentration of the peptide (femtomoles per milligram protein) did not significantly change until the fourth day of food deprivation, when an abrupt decrease in total protein happened and therefore neuromedin B concentration increased. In rats after 20 days of diabetes induction, pituitary neuromedin B increased. Serum thyroxine (T4) and triiodothyronine (T3) decreased in both disorders, whereas serum TSH was normal or decreased in 4-day fasted rats. Therefore, the caloric deprivation of diabetes and fasting changed the pituitary neuromedin B content and concentration, by mechanisms that remain to be elucidated. Since neuromedin B has been shown to act as a local inhibitor of TSH release, the results raise the possibility that increased neuromedin B concentration might be involved in the altered TSH secretion of diabetes mellitus and fasting.

Animals↗
PubMed2003

Scopolamine-induced convulsions in fasted mice after food intake: determination of blood glucose levels, [3H]glutamate binding kinetics and antidopaminergic drug effects.

The present study was performed to evaluate the role(s) of hypoglycemia, changes in [(3)H]glutamate binding kinetics and dopaminergic activity in the occurrence of scopolamine-induced convulsions in fasted mice after food intake. Plasma glucose levels and density (B(max)) and affinity (K(d)) of [(3)H]glutamate binding sites in whole brain synaptic membranes were determined in animals fed ad lib or fasted for 48 h and treated intraperitoneally (i.p.) with 3 mg/kg scopolamine or saline and allowed to eat for 5 min. Fasting for 48 h decreased plasma glucose levels. After refeeding, plasma glucose concentrations increased in saline treated animals, but remained unchanged in scopolamine treated animals which consumed less food. Fasting for 48 h also produced significant changes in the kinetics of [(3)H]glutamate binding. The B(max) and K(d) of the binding sites decreased in fasted animals. These changes were partially antagonized by scopolamine treatment and food intake. For the evaluation of the contribution of dopaminergic activity, another group of mice fasted for 48 h and pretreated (i.p.) with saline or dopamine antagonists, 2 mg/kg chlorpromazine or 2 or 4 mg/kg haloperidol, were treated 10 min later with either saline or 3 mg/kg scopolamine. Then 20 min later, they were allowed to eat ad lib and were observed for 30 min for the incidence and onset of clonic convulsions. Pretreatment of both 2 mg/kg chlorpromazine and 4 mg/kg haloperidol markedly suppressed the convulsions. These results indicate that the decrease in the [(3)H]glutamate binding induced by fasting, its antagonism by scopolamine treatment and food intake, and the dopaminergic hyperactivity may be possible factors contributing to the occurrence of convulsions.

Animals↗
PubMed1999

Enhancing effect of acute fasting on ethanol suppression of pulsatile luteinizing hormone release via an estrogen-dependent mechanism in Holstein heifers.

This study was conducted to determine whether acute fasting in Holstein heifers enhances the suppressive effect of an intravenous injection of ethanol on pulsatile LH release (LH pulse) and, additionally, to establish whether or not the mechanism is estrogen-dependent. After estrus synchronization (Day 0 = estrus), 29 heifers were either fasted (fasting group; n = 14) or fully fed as a control (control group; n = 15) from Days 1 to 4. On Day 4, blood samples were taken at 10-min intervals for 4 h before (pre-injection period) and after (post-injection period) an intravenous injection of 1.5 mL of saline, 1.5 mL of ethanol , or 35 mg of tamoxifen dissolved in 1.5 mL of ethanol . We analyzed the mean LH level, the number of LH peaks per 4 h, and the amplitude of LH peaks. No differences were observed in the LH pulse in the pre-injection period between the control and the fasting group. However, in the post-injection period, compared with the saline injected control heifers, ethanol suppression of the LH pulse was observed in the number of LH peaks of the ethanol injected control heifers and in all pulse parameters of the ethanol injected fasting heifers. Furthermore, tamoxifen inhibited suppression of ethanol on LH pulse was observed in the control and fasting heifers injected with tamoxifen dissolved in ethanol. It was concluded that acute fasting in Holstein heifers has an enhancing effect on ethanol inhibition of the LH pulse and that the mechanism may be estrogen-dependent.

Animals↗
PubMed1997

Short-term fasting alters neonatal rat striatal dopamine levels and serotonin metabolism: an in vivo microdialysis study.

Although frequent feeding is necessary for neonatal brains, rat pups were usually separated from their dams throughout a microdialysis experiment. First, in 5-day-old rats, we examined the effect of probe insertion on initial fluctuation of extracellular striatal monoamines using in vivo microdialysis and subsequent HPLC. Second, fasting effect on monoamine metabolism was examined with or without fasting; the latter was regarded as controls. Extracellular striatal DA in the fasting group decreased promptly to 60% of the basal level in the first 2 h, and reached 50% by the end of the experiment. Dopamine in the fasting group decreased more markedly than in the control group (P < 0.01 by ANOVA) which also decreased to about 80% of the basal level. Extracellular 5-hydroxyindole-3-acetic acid (5-HIAA) continuously increased (P < 0.01), and the serum concentration of tryptophan also increased in the fasting group (P < 0.001). We showed that extracellular striatal monoamine levels fluctuated especially in the first 2 h and fasting altered monoamine metabolism. Therefore, it should take at least 2 h after surgery to stabilize the animals and obtain adequate basal levels. In addition, we should consider that these alterations occur when we use fasting animals as controls in microdialysis studies.

Analysis of Variance↗
PubMed1999

Heterogeneous relationship of early insulin response and fasting insulin level with development of non-insulin-dependent diabetes mellitus in non-diabetic Japanese subjects with or without obesity.

The aim of this study was to investigate the association of insulin secretion and insulin resistance with the development of non-insulin-dependent diabetes mellitus (NIDDM) in obese (body mass index (BMI) > or = 25 kg/m2) and non-obese Japanese. Subjects were selected from persons participating a health survey, and a 100 g oral glucose tolerant test was performed. A total of 1604 non-diabetic subjects were followed for 2-8 years (mean 4.5 years). The fasting insulin level and the homeostasis model insulin resistance index (HOMA-R = fasting glucose [mmol/l] x fasting insulin [microU/ml]/22.5) were used as the index of insulin resistance, and insulinogenic index (the ratio of increment of insulin to that of blood glucose 30 min after glucose load) as a measure of early insulin response. Cox's proportional hazards analysis in the whole group showed that BMI, fasting blood glucose (FBG) and 2-h blood glucose (2-h BG) were positive predictors, and age and insulinogenic index were negative predictors of diabetes. Sex, family history, fasting insulin level and HOMA-R were not predictive of developing diabetes. In subgroup analysis, the same variables as in the whole group were predictors in non-obese, whereas only FBG and 2-h BG predicted diabetes in obese subjects. Fasting insulin level and HOMA-R were not predictive of diabetes both in non-obese and obese subjects. Eleven obese subjects, who developed diabetes despite a normal initial insulinogenic index, had significantly higher BMI, fasting insulin level and HOMA-R, compared with 258 obese subjects who did not develop diabetes. We conclude that most cases of diabetes in Japanese begin with decreased insulin secretion, but a small group of diabetes patients may start with insulin resistance, especially obese subjects.

Adult↗