Some Acute Effects of Intracerebroventricular Neuropeptide Y on Insulin Secretion and Glucose Metabolism in the Rat

Acute administration of neuropeptide Y(NPY) into the hypothalamus and cerebral ventricles can stimulate insulin secretion in the absence of available food. However, the relationship of this effect to blood glucose and other hormones which regulate glucose metabolism remains unclear. The purpose of this study was to compare the effects of NPY injected into the third ventricle (ICV) on serum insulin, glucose, glucagon, corticosterone and non-esterified fatty acids. Studies were performed on conscious, unrestrained female rats, not given access to food. ICV NPY, 2 and 5  μg produced an increase in serum insulin and glucagon, while the 5  μg dose only increased plasma glucose transiently and increased non-esterified fatty acids for a longer period. Corticosterone was not affected by ICV NPY. The insulinaemic response to i.v. glucose, 0.5 g/kg was doubled by ICV NPY, 4  μg. The maximal insulin levels were 113±18 for ICV NPY versus 67±8  μU/ml for ICV saline-treated animals. The glycaemic response was not altered. The hypoglycaemic response to i.v. insulin, 0.15 U/kg was significantly attenuated by ICV NPY, 5  μg. We concluded that ICV NPY promotes insulin secretion in the absence of available food and may potentiate the insulinaemic response to hyperglycaemia. Furthermore, possibly through its effects on glucagon and non-esterified fatty acids, ICV NPY may decrease the ability of insulin to control glucose metabolism.     

Modulation of 14C‐labeled glucose metabolism by zinc during aluminium induced neurodegeneration

Aluminium (Al) is one of the most prominent metals in the environment and is responsible for causing several neurological disorders, including Alzheimer's disease. On the other hand, zinc (Zn) is an essential micronutrient that is involved in regulating brain development and function. The present study investigates the protective potential of Zn in the uptake of ¹⁴C‐labeled amino acids and glucose and their turnover in rat brain slices during Al intoxication. Male Sprague Dawley rats (140–160 g) were divided into four different groups: normal control, Al treated (100 mg/kg body weight/day via oral gavage), Zn treated (227 mg/liter in drinking water), and Al + Zn treated. Radiorespirometric assay revealed an increase in glucose turnover after Al exposure that was attenuated after Zn treatment. Furthermore, the uptake of ¹⁴C‐labeled glucose was increased after Al treatment but was appreciably decreased upon Zn supplementation. In addition, the uptakes of ¹⁴C‐lysine, ¹⁴C‐leucine, and ¹⁴C‐aspartic acid were also found to be elevated following Al exposure but were decreased after Zn treatment. Al treatment also caused alterations in the neurohistoarchitecture of the brain, which were improved after Zn coadministration. Therefore, the present study suggests that Zn provides protection against Al‐induced neurotoxicity by regulating glucose and amino acid uptake in rats, indicating that Zn could be a potential candidate for the treatment of various neurodegenerative disorders. © 2015 Wiley Periodicals, Inc.     

胰岛素治疗对糖尿病大鼠学习记忆功能障碍及大脑皮层额叶和海马神经肽含量变化的影响

目的观察胰岛素治疗对糖尿病大鼠学习记忆功能障碍及大脑皮层、海马内生长抑素(SS)、血管活性肠肽(VIP)含量变化的作用。方法采用链脲菌素制备雄性WiStar大鼠糖尿病模型，设正常对照组、胰岛素治疗糖尿病组、未治疗糖尿病组。3个月后采用T型水迷宫试验测定大鼠学习记忆功能，采用放免法测定皮层额叶、海马区脑组织SS、VIP含量。结果与正常对照组比较，未治疗糖尿病大鼠游迷宫时间显著延长、正确次数显著减少，额叶皮层、海马区脑组织SS含量显著降低，VIP含量无显著变化；胰岛素治疗组大鼠上述变化无显著意义。结论糖尿病引起大鼠学习记忆功能障碍和SS下降；SS下降与学习记忆功能障碍有关；早期胰岛素治疗可使学习记忆功能和SS含量恢复正常。     

Glial cell type‐specific subcellular localization of 14‐3‐3 zeta: An implication for JCV tropism

14‐3‐3 Isoforms are shown to be upregulated or accumulated in the glial cells of autopsied patient brains affected with progressive multifocal leukoencephalopathy (PML), a demylinating disease caused by JC virus (JCV). The possible involvement of 14‐3‐3 in JCV tropism, however, has never been examined. To investigate a potential relationship between 14‐3‐3 isoforms and JCV in vitro, we examined the localization of six 14‐3‐3 isoforms in human neural progenitors and progenitor‐derived astrocytes (PDAs) in cells without JCV exposure. The 14‐3‐3 zeta isoform was initially localized in the progenitor cytoplasm. When differentiation of progenitors into PDAs was induced, the zeta isoform was translocated into the nucleus. However, upon JCV infection, progenitor cells exhibited an uncharacteristic 14‐3‐3 zeta nuclear presence in the few cells that became infected. JCV‐treated PDAs showed elevated levels of 14‐3‐3 zeta compared with noninfected PDAs. Treatment with TGF‐β1, a known stimulant of JCV multiplication, increased the overall number of infected cells and the otherwise absent nuclear presence of 14‐3‐3 zeta in progenitors. These results suggest that the nuclear presence of 14‐3‐3 zeta may play a role in JCV infection, and that the isoform may in part determine JCV susceptibility in these cell types. © 2008 Wiley‐Liss, Inc.     

Hypoglycemia reduces the blood-oxygenation level dependent signal in primary auditory and visual cortex: a functional magnetic resonance imaging study

Studies of the effects of hypoglycemia on the brain using neurocognitive testing have suggested that mainly complex functions subserved by secondary and tertiary cortex are affected by mild to moderate hypoglycemia and that intensively treated patients with Type I diabetes mellitus (T1DM) may have altered sensitivity to the central nervous system effects of hypoglycemia. Functional magnetic resonance imaging provides a sensitive, regionally-specific probe of possible neurophysiologic changes related to hypoglycemia in the brain. Eleven intensively-treated T1DM patients and 11 matched non-diabetic controls took part in a 2-day protocol in which functional magnetic resonance imaging (MRI) was used to measure changes in the patterns of brain activation produced by simple auditory and visual stimuli in different conditions. On one day, participants were euglycemic the entire time. On the other day, an initial 50-min euglycemic period was followed by a 50-min hypoglycemic period. Results indicated that hypoglycemia reduced the amplitude of the blood-oxygenation level dependent response in primary auditory and visual cortex to simple auditory and visual stimuli. The latency and duration of the transient hemodynamic response function were not affected. Responses to hypoglycemia were similar in diabetic and non-diabetic participants. These results suggest that mild to moderate hypoglycemia may alter the balance of blood flow and oxygen extraction when glucose levels are lowered. Intensively-treated T1DM, with its attendant frequent hypoglycemic episodes, did not seem to alter hypoglycemic responses in primary visual and auditory cortex.     

Intracerebroventricular Oxytocin Self‐Administration in Female Rats

Oxytocin (OT) is a neuromodulator that facilitates pair‐bonding, maternal care and social approach. OT is considered to promote these social behaviours by enhancing the salience and reinforcing effects of relevant social stimuli. There is the additional possibility that OT per se may be rewarding. To test this, we investigated whether female rats would voluntarily self‐administer OT. Female Long–Evans rats were ovariectomised and then received an oestrogen implant and an i.c.v. cannula. Rats were tested in an operant chamber with active and inactive levers. They were initially tested for 4 h/day on a fixed‐ratio 5 schedule for self‐administration of artificial cerebral spinal fluid (aCSF) for 5 days, followed by aCSF, or OT, at 1 or 10 ng/μl for another 5 days. Rats self‐administering aCSF made 36.2 ± 6.2 active lever responses/4 h versus 14.9 ± 3.4 inactive responses. Responses for 1 ng/μl OT were similar. However, rats self‐administering 10 ng/μl OT made significantly more active lever responses (67.8 ± 12.0 per 4 h), and received 121.4 ± 21.0 ng OT/4 h. To determine whether reduced anxiety contributes to the reinforcing effects of OT, rats received an infusion of aCSF or OT at 0.3 or 3.0 μg immediately before testing on the elevated plus maze. There was no effect of OT on anxiety as reflected by percentage time spent on the open arms, as well as no effect of OT on locomotion as measured either by the number of closed arm entries or the number of total arm entries. These results suggest that OT may be rewarding, and that this is not a result of the anxiolytic effects of OT.     

Expression of insulin‐like growth factors in remyelination following ethidium bromide‐induced demyelination in the mouse spinal cord

Insulin‐like growth factors, IGF‐I and IGF‐II, play important roles in development and myelination in the CNS, but little is known about the response of IGF after demyelination. The present study investigated the expression of IGF and their cognitive receptors in the process of remyelination following ethidium bromide (EBr)‐induced demyelination in the adult mouse spinal cord. The present results, in a quantitative real‐time PCR, showed significant increases in the levels of the mRNA for both IGF‐I and IGF‐II during both the demyelination and remyelination stages. The levels of IGF‐I receptor (IGF‐IR) mRNA increased from 10 days to 4 weeks after the EBr injection. The levels of IGF‐II receptor (IGF‐IIR) mRNA decreased for 6 days and then increased 10 days after the EBr injection. In situ hybridization studies showed the cells expressing IGF‐I mRNA to be mainly macrophage‐like cells, while those expressing IGF‐II mRNA were predominantly Schwann cell‐like cells invading the demyelinating lesion. The immunoreactivity for the IGF‐IR and IGF‐IIR increased in various kinds of cells within and around the demyelinating lesions from 6 days to 4 weeks after the EBr injection. These results suggest that locally produced IGF could partly be involved in some mechanisms underlying remyelination processes following the EBr‐induced demyelination in the mouse spinal cord.     

Effects of exercise training on hippocampus concentrations of insulin and IGF‐1 in diabetic rats

The present study investigated the role of swimming training on cerebral metabolism and hippocampus concentrations of insulin and IGF‐1 in diabetic rats. Wistar rats were divided in sedentary control (SC), trained control (TC), sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (35 mg kg^?1 b.w.). Training program consisted in swimming 5 days/week, 1 h/day, 8 weeks, supporting a load corresponding to 90% of maximal lactate steady state (MLSS). For MLSS determination, rats were submitted to three sessions of 25‐min supporting loads of 4, 5, or 6% of body wt, with intervals of 1 week. Blood samples were collected every 5 min for lactate determination. An acute exercise test (25 min to 90% of MLSS) was done in 7th week to confirm the efficacy of training. All dependent variables were analyzed by one‐way analysis of variance (ANOVA) and a significance level of P < 0.05 was used for all comparisons. The Bonferroni test was used for post hoc comparisons. At the end of the training period, rats were sacrificed and sample blood was collected for determinations of serum glucose, insulin, GH, and IGF‐1. Samples of gastrocnemius muscle and liver were removed to evaluate glycogen content. Hippocampus was extracted to determinate glycogen, insulin, and IGF‐1 contents. Diabetes decreased serum GH, IGF‐1, and liver glycogen stores in SD. Diabetes also increased hippocampus glycogen and reduced hippocampus IGF‐1 content. Physical training recovered liver and hippocampus glycogen stores and promoted increases in serum IGF‐1 in TD group. Physical training restored hippocampus IGF‐1 content in diabetic group. It was concluded that in diabetic rats, physical training induces important metabolic and hormonal alterations that areassociated with an improvement in glucose homeostasis and with an increased activity in the systemic and hippocampus IGF‐1 peptide. © 2009 Wiley‐Liss, Inc.     

Ischemia preconditioning protects astrocytes from ischemic injury through 14‐3‐3γ

Stroke is a leading cause of death and disability, and new strategies are required to reduce neuronal injury and improve prognosis. Ischemia preconditioning (IPC) is an intrinsic phenomenon that protects cells from subsequent ischemic injury and might provide promising mechanisms for clinical treatment. In this study, primary astrocytes exhibited significantly less cell death than control when exposed to different durations of IPC (15, 30, 60, or 120 min). A 15‐min duration was the most effective IPC to protect astrocytes from 8‐hr‐ischemia injury. The protective mechanisms of IPC involve the upregulation of protective proteins, including 14‐3‐3γ, and attenuation of malondialdehyde (MDA) content and ATP depletion. 14‐3‐3γ is an antiapoptotic intracellular protein that was significantly upregulated for up to 84 hr after IPC. In addition, IPC promoted activation of the c‐Jun N‐terminal kinase (JNK), extracellular signal‐related kinase (ERK)?1/2, p38, and protein kinase B (Akt) signaling pathways. When JNK was specifically inhibited with SP600125, the upregulation of 14‐3‐3γ induced by IPC was almost completely abolished; however, there was no effect on ATP or MDA levels. This suggests that, even though both energy preservation and 14‐3‐3γ up‐regulation were turned on by IPC, they were controlled by different pathways. The ERK1/2, p38, and Akt signaling pathways were not involved in the 14‐3‐3γ upregulation and energy preservation. These results indicate that IPC could protect astrocytes from ischemia injury by inducing 14‐3‐3γ and by alleviating energy depletion through different pathways, suggesting multiple protection of IPC and providing new insights into potential stroke therapies. © 2015 Wiley Periodicals, Inc.     

Vasoactive intestinal peptide is a local mediator in a gut‐brain neural axis activating intestinal gluconeogenesis

Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut‐brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose‐6‐phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP‐positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor‐dependent mechanism in enterocytes.     

Stress Response of Prolactin‐Releasing Peptide Knockout Mice as to Glucocorticoid Secretion

Prolactin‐releasing peptide (PrRP) is known to have functions in prolactin secretion, stress responses, cardiovascular regulation and food intake suppression. In addition, PrRP‐knockout (KO) male mice show obesity from the age of 22 weeks and increase their food intake. The plasma concentrations of insulin, leptin, cholesterol and triglyceride are also increased in obese PrRP‐KO mice. Fatty liver, hypertrophied white adipose tissue, decreased uncoupling protein 1 mRNA expression in brown adipose tissue and glucose intolerance were observed in obese PrRP‐KO mice. As we reported previously, PrRP stimulates corticotrophin‐releasing factor and regulates the hypothalamic‐pituitary‐adrenal axis. Therefore, it is speculated that PrRP regulates both food intake and metabolism as a stress responses. In the present study, we compared blood glucose and plasma glucocorticoid concentrations in PrRP‐KO mice, and found that PrRP‐KO mice showed higher concentrations of blood glucose and corticosterone compared to wild‐type mice after restraint stress. By contrast, there were no difference in c‐Fos expression in the paraventricular hypothalamic nucleus and plasma adrenocorticotrophic hormone concentrations between the two groups. These results suggest that the different stress responses as to glucocorticoid secretion may be induced by different responses of the adrenal glands between wild‐type and PrRP‐KO mice. Thus, we conclude that PrRP‐KO mice become obese as a result of increased food intake, a change in metabolism, and abnormal stress responses as to glucose concentration and glucocorticoid secretion.     

Anticonvulsant and proconvulsant actions of 2‐deoxy‐d‐glucose

Purpose: 2‐Deoxy‐d ‐glucose (2‐DG), a glucose analog that accumulates in cells and interferes with carbohydrate metabolism by inhibiting glycolytic enzymes, has anticonvulsant actions. Recognizing that severe glucose deprivation can induce seizures, we sought to determine whether acute treatment with 2‐DG can promote seizure susceptibility by assessing its effects on seizure threshold. For comparison, we studied 3‐methyl‐glucose (3‐MG), which like 2‐DG accumulates in cells and reduces glucose uptake, but does not inhibit glycolysis. Methods: Mice were treated with 2‐DG or 3‐MG and the seizure threshold determined in the 6‐Hz test, the mouse electroshock seizure threshold (MEST) test, and the intravenous pentylenetetrazol (i.v. PTZ) or kainic acid (i.v. KA) seizure threshold tests. 2‐DG was also tested in fully amygdala‐kindled rats. Results: 2‐DG (125–500 mg/kg, i.p., 30 min before testing) significantly elevated the seizure threshold in the 6‐Hz seizure test. 2‐DG (250–500 mg/kg) decreased the threshold in the MEST and i.v. PTZ and i.v. KA tests. 3‐MG had no effect on seizure threshold in the 6‐Hz test but, like 2‐DG, decreased seizure threshold in the i.v. PTZ test. 2‐DG (250 and 500 mg/kg, i.p., 30 min before testing) had no effect on amygdala‐kindled seizures. Conclusions: Although 2‐DG protects against seizures in the 6‐Hz seizure test, it promotes seizures in some other models. The proconvulsant action may relate to reduced glucose uptake, whereas the anticonvulsant action may require inhibition of glycolysis and shunting of glucose metabolism through the pentose phosphate pathway.     

Central administration of pan‐somatostatin agonist ODT8‐SST prevents abdominal surgery‐induced inhibition of circulating ghrelin,food intake and gastric emptying in rats

Background Activation of brain somatostatin receptors (sst_1–5) with the stable pan‐sst_1–5 somatostatin agonist, ODT8‐SST blocks acute stress and central corticotropin‐releasing factor (CRF)‐mediated activation of endocrine and adrenal sympathetic responses. Brain CRF signaling is involved in delaying gastric emptying (GE) immediately post surgery. We investigated whether activation of brain sst signaling pathways modulates surgical stress‐induced inhibition of gastric emptying and food intake. Methods Fasted rats were injected intracisternally (i.c.) with somatostatin agonists and underwent laparotomy and 1‐min cecal palpation. Gastric emptying of a non‐nutrient solution and circulating acyl and desacyl ghrelin levels were assessed 50 min post surgery. Food intake was monitored for 24 h. Key Results The abdominal surgery‐induced inhibition of GE (65%), food intake (73% at 2 h) and plasma acyl ghrelin levels (67%) was completely prevented by ODT8‐SST (1 μg per rat, i.c.). The selective sst₅ agonist, BIM‐23052 prevented surgery‐induced delayed GE, whereas selective sst₁, sst₂, or sst₄ agonists had no effect. However, the selective sst₂ agonist, S‐346‐011 (1 μg per rat, i.c.) counteracted the abdominal surgery‐induced inhibition of acyl ghrelin and food intake but not the delayed GE. The ghrelin receptor antagonist, [D‐Lys³]‐GHRP‐6 (0.93 mg kg^?1, intraperitoneal, i.p.) blocked i.p. ghrelin‐induced increased GE, while not influencing i.c. ODT8‐SST‐induced prevention of delayed GE and reduced food intake after surgery. Conclusions & Inferences ODT8‐SST acts in the brain to prevent surgery‐induced delayed GE likely via activating sst₅. ODT8‐SST and the sst₂ agonist prevent the abdominal surgery‐induced decrease in food intake and plasma acyl ghrelin indicating dissociation between brain somatostatin signaling involved in preventing surgery‐induced suppression of GE and feeding response.     

Effect of Deletion of Ghrelin‐O‐Acyltransferase on the Pulsatile Release of Growth Hormone in Mice

Ghrelin, a gut hormone originating from the post‐translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS‐R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin‐O‐acyltransferase (GOAT), conferring selective binding to the GHS‐R1a receptor via acylated ghrelin. Complete loss of preproghrelin‐derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl‐ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat^?/? mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat^?/? mice compared to age‐matched wild‐type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH‐dependent liver genes. Of interest, circulating levels of insulin‐like growth factor (IGF)‐1 were elevated in goat^?/? mice. This rise in circulating levels of IGF‐1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF‐1 release in goat^?/? mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF‐1 release and growth in goat^?/? mice.     

Short‐term fasting promotes insulin expression in rat hypothalamus

In the hypothalamus, insulin takes on many roles involved in energy homoeostasis. Therefore, the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and Western blot. The relative expression of insulin mRNA was examined by qPCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After 6‐h fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short‐term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular.     

The Effect of Intracerebroventricular Administration of Somatostatin on Prolactin and TSH Release in Rats

Abstract: We investigated the effect of intracerebroventrciular (icv) administration of somatostatin (SRIF) on prolactin (PRL) and thyroid-stimulating hormone (TSH) release in freely moving rats chronically cannulated with en atrial catheter. The plasma PRL levels were significantly elevated following the icv administration of 0.5 ug SRIF. No further increase in PRL following the icv administration of SRIF were found in the rats in the course of repeated intravenous of injection of 5.0 mg/kg sulpiride, a specific D2 receptor antagonist. On the other hand, the injection of 5.0 /ig SRIF resulted in no significant change in the plasma TSH levels. These results suggest that the effect of SRIF on PRL release was exerted through brain D2 receptors.     

Synchronization of intrinsic 0.1‐Hz blood‐oxygen‐level‐dependent oscillations in amygdala and prefrontal cortex in subjects with increased state anxiety

Low‐frequency oscillations with a dominant frequency at 0.1 Hz are one of the most influential intrinsic blood‐oxygen‐level‐dependent (BOLD) signals. This raises the question if vascular BOLD oscillations (originating from blood flow in the brain) and intrinsic slow neural activity fluctuations (neural BOLD oscillations) can be differentiated. In this study, we report on two different approaches: first, on computing the phase‐locking value in the frequency band 0.07–0.13 Hz between heart beat‐to‐beat interval (RRI) and BOLD oscillations and second, between multiple BOLD oscillations (functional connectivity) in four resting states in 23 scanner‐naïve, anxious healthy subjects. The first method revealed that vascular 0.1‐Hz BOLD oscillations preceded those in RRI signals by 1.7 ± 0.6 s and neural BOLD oscillations lagged RRI oscillations by 0.8 ± 0.5 s. Together, vascular BOLD oscillations preceded neural BOLD oscillations by ~90° or ~2.5 s. To verify this discrimination, connectivity patterns of neural and vascular 0.1‐Hz BOLD oscillations were compared in 26 regions involved in processing of emotions. Neural BOLD oscillations revealed significant phase‐coupling between amygdala and medial frontal cortex, while vascular BOLD oscillations showed highly significant phase‐coupling between amygdala and multiple regions in the supply areas of the anterior and medial cerebral arteries. This suggests that not only slow neural and vascular BOLD oscillations can be dissociated but also that two strategies may exist to optimize regulation of anxiety, that is increased functional connectivity between amygdala and medial frontal cortex, and increased cerebral blood flow in amygdala and related structures.     

氯氮平对雄性小鼠血糖和胰岛素的影响

目的：探讨氯氮平对雄性C57BL／6小鼠血糖和胰岛素的影响。方法：63只雄性C57BL／6小鼠随机分为3大组,空白组、氯氮平4mg／kg组、氯氮平20mg／kg组,于灌药后的3h、1周、4周测定空腹血糖、糖耐量、胰岛素。结果：灌药后3h、l周空腹血糖、血胰岛素、血糖曲线下面积都无显著升高;灌药4周后空腹血糖值显著升高。腹腔注射高糖后60min的氯氮平20mg/kg组的血糖值及血胰岛素显著升高,结诊：氯氮可以慢性升高小鼠的空腹血糖和胰岛素,影响糖耐量,但急性期无明显影响。