Effects of body temperature maintenance on glucose, insulin, and corticosterone responses to acute hypoxia in the neonatal rat

One of the biggest challenges of premature birth is acute hypoxia. Hypothermia during acute hypoxic periods may be beneficial. We hypothesized that prevention of hypothermia during neonatal hypoxia disrupts glucose homeostasis and places additional metabolic challenges on the neonate. Pups at PD2 and PD8 were exposed to 8% O2 for 3 h, during which they were allowed to either spontaneously cool or were kept isothermic. There was also a time control group that was subjected to normoxia and kept isothermic. Plasma glucose, insulin, C-peptide, corticosterone, and catecholamines were measured from samples collected at baseline, 1 h, 2 h, and 3 h. In postnatal day 2 (PD2) rats, hypoxia alone resulted in no change in plasma glucose by 1 h, an increase by 2 h, and a subsequent decrease below baseline values by 3 h. Hypoxia with isothermia in PD2 rats elicited a large increase in plasma insulin at 1 h. In PD8 rats, hypoxia with isothermia resulted in an initial increase in plasma glucose, but by 3 h, glucose had decreased significantly to below baseline levels. Hypoxia with and without isothermia elicited an increase in plasma corticosterone at both ages and an increase in plasma epinephrine in PD8 rats. We conclude that the insulin response to hypoxia in PD8 rats is associated with an increase in glucose similar to an adult; however, insulin responses to hypoxia in PD2 rats were driven by something other than glucose. Prevention of hypothermia during hypoxia further disrupts glucose homeostasis and increases metabolic challenges.     

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

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

Influence of insulin-like growth factor-1 and leptin on bone mineral content in healthy premenopausal women

The aim of the present investigation was to study the influence of plasma insulin-like growth factor-1 (IGF-1) and leptin levels on bone mineral mass (BMC) and bone mineral density (BMD) in premenopausal women and the relationship between IGF-1 and leptin levels. Two hundred and four healthy women participated in this study. All participants had a body mass index (BMI) <30 kg/m(2) and were matched for their level of mean daily energy expenditure. BMC and BMD were correlated with measured body composition and blood biochemical parameters. No association was observed between BMC and BMD values with measured physical performance characteristics. Leptin had a significant association with BMC (beta = 0.840; P = 0.0001), total BMD (beta = 0.833; P = 0.0001), femoral neck BMD (beta = 0.829; P = 0.0001), and lumbar spine BMD (beta = 0.833; P = 0.0001). However, these associations were no longer independent when adjusted for body fat mass (FM) and trunk fat:leg fat ratio (P > 0.385). IGF-1 was significantly related to BMC (beta = 0.920; P = 0.0001), total BMD (beta = 0.918; P = 0.0001), femoral neck BMD (beta = 0.921; P = 0.0001), and lumbar spine BMD (beta = 0.917; P = 0.0001), but did not remain significant when adjusted for fat free mass (FFM; P > 0.062). In addition, a significant association between IGF-1 and leptin was found (beta = 0.801; P = 0.0001), and it remained significant after controlling for age, FM, FFM, insulin, and fasting insulin resistance index (FIRI), but not when adjusted for BMC and body mass values. In conclusion, it appears that fasting IGF-1 and leptin concentrations have no direct effect on BMC and BMD values. In addition, if there is an important relationship between IGF-1 and leptin, it is mediated or confounded by BMC in premenopausal women.     

Effects of hypersecretion of growth hormone and prolactin on plasma levels of glucagon and insulin in GH3-cell-tumor-bearing rats, and the influence of bromocriptine treatment

Plasma levels of prolactin, growth hormone, glucagon insulin and glucose were measured in non-treated control rats, bromocriptine-treated control rats and GH3-cell-tumor-bearing rats with and without bromocriptine treatment. Bromocriptine treatment increased plasma levels of glucagon, insulin and glucose in control rats. Tumor-bearing rats had increased body weight and increased plasma levels of prolactin, growth hormone, glucagon, insulin and glucose. Bromocriptine treatment reduced body weight and decreased the plasma levels of prolactin, glucagon and insulin, as compared to non-treated tumor-bearing rats. The drug had no effect on plasma levels of growth hormone and glucose. These results indicate that, in GH3-cell-tumor-bearing rats, prolactin, glucagon and insulin are more sensitive to the action of bromocriptine than growth hormone.     

Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats

Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88?±?5.69 mmol/L vs. 14.79?±?5.84 mmol/L, p?<?0.05), while it was not different in diabetic rats after hypoxic treatment (13.14?±?5.77 mmol/L vs. 14.79?±?5.84 mmol/L, p?>?0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28?±?0.11 vs. 1.39?±?0.11, p?<?0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48?±?0.48 vs. 3.86?±?0.42, p?<?0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular glycogenesis may play a role in the underlying mechanism.     

Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents

Objective: To characterize a model of atypical antipsychotic drug‐induced obesity and evaluate its mechanism. Research Methods and Procedures: Chronically, olanzapine or clozapine was self‐administered via cookie dough to rodents (Sprague‐Dawley or Wistar rats; C57Bl/6J or A/J mice). Chronic studies measured food intake, body weight, adiponectin, active ghrelin, leptin, insulin, tissue wet weights, glucose, clinical chemistry endpoints, and brain dopaminergic D2 receptor density. Acute studies examined food intake, ghrelin, leptin, and glucose tolerance. Results: Olanzapine (1 to 8 mg/kg), but not clozapine, increased body weight in female rats only. Weight changes were detectable within 2 to 3 days and were associated with hyperphagia starting ～24 hours after the first dose. Chronic administration (12 to 29 days) led to adiposity, hyperleptinemia, and mild insulin resistance; no lipid abnormalities or changes in D2 receptor density were observed. Topiramate, which has reversed weight gain from atypical antipsychotics in humans, attenuated weight gain in rats. Acutely, olanzapine, but not clozapine, lowered plasma glucose and leptin. Increases in glucose, insulin, and leptin following a glucose challenge were also blunted. Discussion: A model of olanzapine‐induced obesity was characterized which shares characteristics of patients with atypical antipsychotic drug‐induced obesity; these characteristics include hyperphagia, hyperleptinemia, insulin resistance, and weight gain attenuation by topiramate. This model may be a useful and inexpensive model of uncomplicated obesity amenable to rapid screening of weight loss drugs. Olanzapine‐induced weight gain may be secondary to hyperphagia associated with acute lowering of plasma glucose and leptin, as well as the inability to increase plasma glucose and leptin following a glucose challenge.     

In Zucker diabetic fatty rats plasma leptin levels are correlated with plasma insulin levels rather than with body weight.

The obese (ob) gene product leptin, secreted from adipose tissue, acts in the hypothalamus to regulate body energy stores. In vitro experiments showed that insulin increases both leptin mRNA expression and leptin secretion by adipocytes. Here, we report on the relationship between plasma insulin and plasma leptin in a longitudinal in vivo study. In Zucker diabetic fatty (ZDF) rats, an animal model for non-insulin-dependent diabetes mellitus (NIDDM), and in ZDF control rats, blood glucose, body weight, plasma insulin and plasma leptin levels were measured from 10 to 25 weeks of age. In ZDF control rats, body weight, plasma leptin and plasma insulin levels increased gradually during the study period. In ZDF rats, the time course of plasma leptin was similar to that of plasma insulin, but did not parallel that of body weight. Calculation of partial correlation coefficients revealed that in ZDF control rats plasma leptin correlated with body weight rather than with plasma insulin. However, in ZDF rats, plasma leptin correlated with plasma insulin rather than with body weight, suggesting an important role for insulin in the modulation of leptin secretion in this animal model for NIDDM.     

Plasma Insulin in Response to Enterostatin and Effect of Adrenalectomy in Rats

Enterostatin has previously been reported to alter serum insulin and corticosterone levels after central administration of the peptide. The purpose of the present study was to investigate the effect of peripheral administration of enterostatin on insulin and corticosterone levels as well as the response of plasma insulin to enterostatin administration in adrena-lectomized rats. Female Sprague-Dawley rats were given a bolus injection intravenously with enterostatin alone or together with glucose. Enterostatin increased basal plasma levels of insulin, but significantly inhibited the increase in plasma insulin stimulated by glucose. Plasma corticosterone levels were not altered after a single intravenous injection of enterostatin. In rats infused chronically with enterostatin, plasma insulin levels were significantly reduced and plasma corticosterone levels were increased. The daily food intake was lower in these rats, but there was no effect on body weight. After adrenalectomy, the responsiveness of plasma insulin to enterostatin infusion was completely abolished. Furthermore, adrenalectomy itself reduced basal plasma levels of insulin and increased plasma levels of endogenous enterostatin. These results suggest that peripheral enterostatin administration produces a similar effect as central infusion of the peptide, and that the glucocorticoid hormones are involved in the regulation of plasma insulin by enterostatin.     

The effect of fasting and physical exercise on plasma leptin concentrations in high-fat fed rats.

The aim of our study was to estimate the effect of fasting and physical exercise on a treadmill on plasma leptin concentrations in high-fat fed rats. Male Wistar rats were injected a low dose of streptozotocin (STZ) or buffer at 2 days of age and later fed a standard or high-fat diet (HFD). Plasma leptin was measured by RIA method in all the groups studied in basal conditions, after 48h fasting, a single bout of exhaustive exercise, and 4 weeks of exercise training. Plasma leptin concentrations were markedly elevated in the HFD and STZ/HFD groups compared to the control group. The significant correlation between plasma leptin and body weight was noted. Fasting and exercise training decreased plasma leptin in similar percentage in all the groups studied. The observed decrease was greater than expected from changes in body weight. We conclude that high-fat feeding results in an increase in plasma leptin levels in rats independently of plasma insulin or daily calorie intake. High-fat fed rats have maintained leptin response to fasting and exercise training. The reduction in plasma leptin after exercise training is partly independent on changes in body weight or plasma insulin.     

Severe pulmonary hypertension in aging female apolipoprotein E-deficient mice is rescued by estrogen replacement therapy

Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. Male and female CRF-OE mice and WT littermates (4–6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals. Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females. These data indicate that CRF-OE mice have abnormal basal and fasting circulating hormones and hypothalamic feeding-related signals. CRF-OE also abolishes the sex difference in body weight, abdominal fat, and fasting-induced feeding and changes in plasma levels of leptin and acyl ghrelin.     

Mirex-induced liver enlargement in rats is dependent upon an intact pituitary-adrenalcortical axis

The effect of prior hypophysectomy upon mirex-induced liver hypertrophy in male Sprague-Dawley rats was examined. Mirex had no effect upon adrenal weight, liver weight, plasma glucose or plasma corticosterone in hypophysectomized rats. However, daily corticosterone supplements (20 mg/kg body weight, sc) given to mirex-treated hypophysectomized animals yielded a 52% increase in liver weight to body weight ratios over those observed in mirex-treated hypophysectomized animals not receiving supplement. In intact rats, both liver weight to body weight ratios and plasma ACTH were significantly increased over controls 2 days after mirex treatment. These results indicate that mirex-induced liver enlargement not only requires corticosterone, but that the response is dependent upon an intact pituitary-adrenalcortical axis.     

不同强度有氧跑有助于改善IGR老年人的症状

为了探讨不同强度持续跑步干预对糖调节受损(impaired glucose regulation,IGR)人群胰岛素敏感性、骨密度、糖调节、激素分泌的影响效果差异,为研发促进IGR人群糖调节能力恢复的运动处方提供实证参考,本研究选定90名糖调节受损老年人为本研究实验对象,进行随机分组,随机分为Fatmax强度跑步组(F组,n=30);AT强度跑步组(A组,n=30);对照组(C组,n=30)。在干预开始前1周内对受试者进行前测(BMD,骨代谢,FPG,OGTT-2h,HOMA-IR,IGF-1,生长激素分泌指标)。干预前3天,F组进行FATMAX强度测试、A组进行AT强度测试,各组按照运动计划进行为期24周的干预,运动干预结束后测。通过24周干预,F组和A组受试者的BMI、体脂率后测结果显著低于前测结果(p<0.05),而C组BMI和体脂率前后测结果对比没有显著性差异(p>0.05);F组、A组的FPG和OGTT-2h后测结果显著低于前测,且显著低于C组后测结果(p<0.05);F组和A组受试者的血清GH、IGF-1以及BGP的后测结果明显高于其前测结果和C组后测结果(p<0.05),而C组GH、IGF-1和BGP前后测结果对比没有显著性差异(p>0.05)。F组和A组受试者股骨颈BMD、大转子骨BMD、Ward’s三角区BMD后测结果显著高于前测结果和C组后测结果(p<0.05)。IGR老年人长期进行以Fatmax和AT强度进行长时间有氧跑步,不仅能够增加其下肢骨密度、促进骨生产和改善骨代谢,而且降低FPG、缓解胰岛素抵抗、促进GH、IGF-1分泌。其机制可能是IGR老年人长期进行中低强度有氧跑会提升血清GH、IGF-1浓度,而GH和IGF-1能够促进胰岛素的分泌合成以及促进成骨细胞工作,从而缓解IGR老年人的胰岛素抵抗和增加下肢BMD。     

Effect of aging on 24-hour pattern of stress hormones and leptin in rats

This work analyzes the 24-hour changes of hypothalamic-pituitary-adrenal (HPA) axis activity and leptin release in aged rats. Three- and 22-month-old male Wistar rats were killed at 6 time intervals during a 24-hour cycle (n=8-10 rats/group). Aging augmented plasma ACTH while it decreased plasma and adrenal gland corticosterone levels. Plasma and adrenal corticosterone levels attained high levels during all the scotophase, concomitantly with the maxima in ACTH levels, whereas in aged rats only a brief plasma corticosterone peak at the early scotophase and no time of day variations of adrenal corticosterone were observed. Aging augmented circulating leptin, with a significant interaction "agextime" in the factorial ANOVA, i.e. only in young rats time of day changes were significant, with the lowest values of leptin at the middle of the light period and higher values at night. When plasma leptin was expressed on body weight basis, the age-related differences became not significant but the daily pattern of plasma leptin found in young rats persisted. Plasma and adrenal corticosterone levels correlated significantly with plasma ACTH only in young rats. Likewise, plasma leptin correlated with plasma corticosterone only in young rats. These changes can be attributed to a disrupting effect of aging on the homeostatic mechanisms modulating HPA activity and leptin release.     

Central application of IGF-1 postpones time of vaginal opening in normally fed, but not in food-restricted rats

BACKGROUND/AIMS: Central but also peripheral IGF-1 is suggested to play a role in the initiation of puberty as it directly affects GnRH synthesis and release. A possible intermediate in the effects of IGF-1 on puberty might be the adiposity-signaling hormone leptin, whose plasma levels are decreased in food-restricted (FR) rats. METHODS: IGF-1 was chronically centrally infused in 23-day-old prepubertal female rats which were either normally fed or 30% FR, and the effects on time of vaginal opening (VO) and plasma leptin levels were monitored. RESULTS: FR treatment postponed time of VO and decreased plasma leptin levels. In normally fed rats centrally infused with IGF-1, time of VO was found to be postponed to the same extent as FR treatment did. The IGF-1 infusion did not affect plasma leptin levels in normally fed animals but increased leptin levels in the FR group compared to controls. Daily food intake was equal between all groups but body weight course was lower in FR rats. IGF-1 treatment did not significantly affect food intake or body weight course. CONCLUSION: FR treatment delays the moment of vaginal opening to the same extent as observed in normally fed rats that were centrally infused with IGF-1.     

Effects of Intracerebroventricular Infusion of Leptin in Obese Zucker Rats

AL-BARAZANJI, KAMAL A, ROBIN E BUCKINGHAM, JONATHAN RS ARCH, ANDREA HAYNES, DANUTA E MOSSAKOWSKA, DIANE L McBAY, STEPHEN D HOLMES, MARK T McHALE, XIN-MIN WANG, ISRAEL S GLOGER. Effects of intracerebro-ventricular infusion of leptin in obese Zucker rats. The obese Zucker rat (OZR) exhibits a missense mutation in the cDNA for the leptin receptor, producing a single amino acid substitution in the extracellular domain of the receptor. A mutation in the leptin receptor gene of the db/db mouse prevents the synthesis of the long splice variant of the receptor. The possibility that the OZR, like the db/db mouse, is refractory to the actions of murine leptin was tested by infusing the protein intracerebroventricularly via a minipump for 7 days. Lean Zucker rats (LZR) infused with leptin acted as positive controls, and other groups of OZR and LZR were infused with vehicle. In LZR, leptin reduced body-weight and food intake and increased brown adipose tissue (BAT) temperature. Plasma corticosterone increased (61%) in these rats, and plasma triglycerides fell (78%). Leptin treatment improved tolerance to an oral glucose load (16% reduction in the area under the blood glucose curve) while lowering plasma insulin. In OZR, the actions of leptin were blunted. Food intake was slightly, but not significantly, reduced. Although there was a reduction in the rate of increase in body mass, the effect of leptin was about half that seen in LZR. BAT temperature and glucose tolerance were unchanged. In contrast to the elevated plasma corticosterone seen in LZR, leptin reduced the level of this hormone (27%) in OZR. In OZR and LZR treated with leptin, the plasma leptin levels were increased 24-fold and 47-fold, respectively. The results suggest that leptin retains some efficacy in OZR, although these rats are less responsive than LZR.     

Early Neuroendocrine Alterations in Female Rats Following a Diet Moderately Enriched in Fat

1. High-fat diets disrupt metabolic equilibrium and hypothalamic-pituitary-adrenal axis function and may lead to the development of metabolic and endocrine dysfunctions. The early neuroendocrine responses elicited by a combination of short-term metabolic and emotional stressors is not fully elucidated. 2. The purpose of the present study was to determine the impact on female rats, of a short-term enriched in fat diet, combined with an acute stressor. 3. Adult female Wistar rats were fed a fat diet for 7 days and subsequently exposed to 5 min swimming stress. Plasma leptin, insulin, glucose, luteinizing hormone (LH) and corticosterone, along with brain corticosteroid receptors' mRNAs were measured at 1 h post stress. 4. Diet, compared to chow, reduced food intake and body weight gain, increased leptin and LH, and decreased glucose in the periphery. The diet increased plasma corticosterone and reduced GR mRNA in the hippocampus, similarly to swim stress. 5. The diet significantly modified the animals' response to the subsequent swim stress, by blocking further corticosterone rise and GR mRNA reduction. In addition, exposure of diet-fed rats to stress, altered their endocrine response, in terms of leptin and LH. 6. These observations suggest that even short, moderately unbalanced diets can affect peripheral and central components of energy balance, reproduction and stress response.     

Subchronic treatment with metformin produces anorectic effect and reduces hyperinsulinemia in genetically obese Zucker rats.

The effect of subchronic metformin treatment on food intake, weight gain and plasma and tissue hormone levels was investigated in genetically obese male Zucker rats and in their lean controls. Metformin hydrochloride (320 mg/kg/day for 14 days in the drinking water) significantly reduced 24 hour food intake both after one and two weeks treatment in obese rats. In contrast, metformin had only a transient effect on food intake in lean animals. The reduced food intake was associated with body weight decrease, particularly in obese rats. Metformin markedly reduced also the hyperinsulinemia of the obese animals without altering their plasma glucose or pancreatic insulin content which may reflect an improved insulin sensitivity after metformin treatment. Metformin did not change plasma corticosterone levels or insulin and somatostatin concentrations in the pancreas. Metformin reduced pyloric region somatostatin content in lean rats. It is concluded that metformin has an anorectic effect and reduces body weight and hyperinsulinemia in genetically obese Zucker rat.     

Dynamics of food intake and blood level of hormones regulating appetite in pregnant and lactating mice

Leptin, insulin, corticosterone regulate food intake. Hyperphagia and hormonal rearrangement are typical for pregnancy and lactation. The aim of the study is to correlate food intake with blood levels of these hormones in pregnant and lactating mice. Food intake, body weight, blood glucose, insulin, leptin and corticosterone levels were measured in virgin C57B1/6J micc and on the day 7, 13,17 of pregnancy, and day 1, 7, 14, 30 postpartum. Insulin sensitivity was measured at the day 7, 17 of pregnancy. Food intake and body weight increased towards the second postpartum week and then decreased. Insulin sensitivity decreased towards the end of the pregnancy. Mothers differed from virgin females in hormones and glucose levels only during pregnancy. Leptin level was decreased at the day 7 of gestation, insulin level - during whole gestation. Glucose fell, and leptin and corticosterone increased from the day 7 to 17. Probably, these hormones affect food intake only in pregnant females and do not influence appetite during lactation.     

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.     

Angiotensin II stimulates the reactivity of the pituitary-adrenal axis in leptin-resistant Zucker rats, thereby influencing the glucose utilization

The HPA axis is hyperactive under conditions of leptin and insulin resistance as well as after ANG II administration. We hypothesized that a hyperreactivity of the HPA axis to ANG contributes to an impaired glucose utilization in obesity, since leptin resistance and an overactive renin-angiotensin-aldosterone system are features of obesity. Zucker rats were treated with ANG via subcutaneous minipumps (0, 0.9, and 9.0 mug/h; 4 wk). PA axis reactivity and glucose homeostasis were characterized after CRH treatment and during an oral glucose tolerance test (OGTT). The elevated plasma profile of corticosterone after CRH stimulation in saline-treated OZR compared with LZR confirmed that the sensitization of the PA axis depended on leptin resistance. Irrespective of the rat strain, circulating ANG levels and blood pressure were selectively increased after administration of 9 mug/h ANG (high ANG). Only high ANG induced an elevation of the corticosterone and glucose response after CRH stimulation in OZR but did not affect the ACTH secretion. During OGTT, corticosterone and consequently glucose increased in OZR after high ANG, whereas the insulin secretion was decreased. In the adrenal glands of OZR, AT(1A) receptor mRNA levels increased after high ANG. We conclude that the impairment of glucose utilization after ANG stimulation is potentiated in leptin-resistant rats as a result of a hyperreactive PA axis, thereby confirming the functional importance of a dysregulation within the HPA axis in metabolic syndrome or obesity. The ACTH-independent stimulation of corticosterone release and the selective increase of AT(1A) receptor mRNA in the adrenals of OZR indicated a sensitization of adrenals toward ANG, causing a stimulation of the PA axis.