家鸽顶盖脑片中Ⅱ g—j亚层神经元对乙酰胆碱的反应

在家鸽的离体顶盖脑片上，用玻璃微电极记录了顶盖Ⅱg-j亚层神经元对灌流乙酰胆碱所产生的反应，结果如下：在顶盖IIg-j亚层记录到66个神经元的自发放电，根据其放电特征，将它们分为3种形式：单个放电，丛状放电和连续放电，其中的46个神经元单位中有34个（34／46）对 酰胆碱产生自发放电增频反应；4个单位（4／46）的自发放电被乙酰胆碱抑制；8个单位（8／46）对乙酰胆碱无反应，在20个对乙酰胆碱产生增频反应的神经元单位中，有14个单位（14／20）的自发放电被阿托品所抑制，乙酰胆碱和阿托品的作用还具有可逆性的重复性，以上结果提示：在家鸽顶盖IIg-j亚层中可能有胆碱能纤维到达并存在乙酰胆碱敏感神经元。     

缰核参与应激性高血压的形成及其神经元c—fos蛋白表达与细胞凋亡的探讨

缰核(Habenulae,Hb)是边缘系统与脑干联络的中继站.本工制备了应激性高血压大鼠,测定应激后大鼠血浆中血管紧张素II(AII)的浓度及缰核在应激下神经元的c—fos蛋白表达与细胞凋亡现象,目的是探讨缰核在调节心血管活动方面发挥的作用.结果表明,正常血压大鼠可在被应激半个月内变成高血压大鼠,在急性应激2小时之时AII在血浆内的浓度可达最高,应激2小时之时的缰核c—fos蛋白表达也在几个应激组为最多,提示血浆内AII与缰核c—fos蛋白表达有相关性.慢性应激致缰核神经元细胞凋亡及大鼠形成应激性高血压表明,参与血压调节的神经元损伤后调节血压能力下调,可能致使动物血压进一步升高.     

运动疲劳大鼠丘脑腹外侧核神经元自发放电特征的分析

通过观察力竭运动对大鼠丘脑腹外侧核(VL)神经元自发放电活动的影响,探讨丘脑腹外侧核在运动疲劳中枢调控过程中的作用.选取雄性Wistar大鼠,随机分为对照组和疲劳组.采用跑台递增负荷运动方案,建立运动疲劳模型.采用玻璃微电极的体电生理学技术,观察丘脑腹外侧核神经元自发放电活动,并对其放电模式、放电频率、锋电位间隔直方图进行线下分析.得到了FG大鼠丘脑腹外侧核单簇发混合放电和规则单发放电神经元比例明显低于CG(P0.01),爆发式放电神经元比例明显高于CG(P0.01).FG大鼠丘脑腹外侧核神经元总放电频率显著低于CG(P0.05),规则单发放电频率有所升高,单簇发混合放电频率有所降低,但与CG相比均未见显著差异(P0.05).可以看出大鼠丘脑腹外侧核神经元参与了运动性疲劳的中枢调控.丘脑腹外侧核在运动疲劳引起间接通路与直接通路的调节功能失衡过程中起关键作用.     

侧脑室注射腺苷对家兔尾核痛神经元自发放电活动的影响

采用侧脑室给药法及常规神经元放电引导法,研究了腺苷(Ado)对家兔尾核痛神经元自发放电的影响及其可能机制.结果表明Ado能不同程度的抑制尾核痛神经元自发放电活动,且呈明显的剂量依赖性.其作用机理可能与Ado和其A1受体结合后,间接激活ATP敏感性K 通道,引起尾核痛神经元细胞膜超极化有关.     

金匮肾气丸对四氧嘧啶糖尿病模型大鼠的降糖作用研究

观察金匮肾气丸对四氧嘧啶糖尿病大鼠的降糖作用,探讨金匮肾气丸治疗糖尿病的应用。方法：给予四氧嘧啶糖尿病大鼠金匮肾气丸方煎剂,连续4周后,测定其空腹血糖、胰岛素、胰高血糖素和血脂水平。结果：与模型组比较,金匮肾气丸组空腹血糖、胰高血糖素、TC、TG、LDL-C水平明显降低（P〈0.05或P〈0.01）;HDL-C水平明显升高（P〈0.05）;胰岛素水平有增高趋势,但无统计学意义（P〉0.05）。结论：金匮肾气丸对四氧嘧啶糖尿病大鼠有明显降糖、调脂作用。     

GLP-1及其类似物调节β细胞增殖的分子机制

胰高血糖素样肽1(Glucagon-like peptide1,GLP-1)是一种L细胞产生的内源性激素,其主要作用是调节胰岛素和胰高血糖素的分泌;越来越多的研究结果表明,GLP-1及其类似物通过激活其受体,在调节胰岛β细胞的增殖和分化、抑制细胞凋亡、促进胰岛素释放、降低血糖以及改善糖耐量等方面都有十分重要的作用;近年来,特别是有关GLP-1及其类似物激活其受体引起的下游细胞信号转导机制有大量的报道,现就GLP-1及其类似物调节β细胞增殖的分子机制及细胞信号转导途径进行综述。     

5-HT_(2C)受体对帕金森病模型大鼠外侧缰核谷氨酸能神经元电活动的影响

为探讨帕金森病(PD)模型大鼠外侧缰核(LHb)中谷氨酸能神经元的电活动变化及其对5-羟色胺2C(5-HT_(2C))受体刺激的反应,阐明LHb和5-HT_(2C)受体在PD神经生物学机制中发挥的作用,通过6-羟多巴胺(6-OHDA)损毁单侧黑质致密部(substantia nigra pars compacta,SNc)建立PD模型,采用细胞外记录的方法,观察假手术组与单侧SNc损毁组大鼠LHb中谷氨酸能神经元的电活动。结果显示:与假手术组大鼠相比,损毁组大鼠LHb中谷氨酸能神经元的电活动增强,表现为爆发式放电活动增强(P0.05);LHb中局部注射5-HT_(2C)受体激动剂Ro60-0175后,两组大鼠的神经元放电频率虽均升高(P0.05),但损毁组大鼠LHb中谷氨酸能神经元放电频率升高持续时间显著长于假手术组,且给药前后神经元的放电形式更趋向于爆发式活动(P0.05),变异系数明显升高(P0.05)。结果提示单侧SNc损毁使LHb中谷氨酸能神经元爆发式电活动增强,可能与PD相关抑郁行为发生有关,5-HT_(2C)受体参与了对LHb中谷氨酸能神经元电活动的调节。     

采用胰高血糖素刺激C-肽释放实验判定糖尿病患者的β细胞功能

为评估糖尿病患者β细胞胰岛素分泌功能，采用胰高血糖素刺激C-肽释放试验评估糖尿病患者β细胞分泌功能，结果表明：在本组1型及2型糖尿病患者中，空腹及胰高血糖素刺激6min后血浆C-肽值差别明显；胰高血糖素刺激C-肽释放试验是一种简单可行、方便、重复性好的判断糖尿病患者β细胞分泌功能的方法。     

电刺激岛叶对大鼠血压及缰核内神经元放电活动的影响

研究证明了缰核（Hb)是刺激岛叶（INS）所引起的升压效应下行通路的主要中继站之一。电刺激INS引起升压反应，在刺激电极的同侧Hb内微量注射盐酸利多卡因，电刺激INS所引起的升压反应降低了36.9%。双侧Hb内微量注射盐酸利多卡因，电刺激INS所引起的升压反应降低了41．7％。单侧或双侧Hb内微量注射生理盐水或人工脑脊液均不能降低电刺激INS所引起的升压反应。在刺激INS前后用微电极记录Hb内心血管调节相关神经元放电活动的变化。电刺激INS后，Hb内心血管调节相关神经元的放电频率明显增加者占58％（21／36），频率明显减少者占14％（5／36），频率无明显变化者占28％（10／36）。结论表明：缰核是参与电刺激岛叶引起升压效应的主要下行通路之一。     

胰高血糖素免疫敏感膜的制备及SPR检测

制备胰高血糖素免疫敏感膜并建立一种快速、简便测定胰高血糖素含量的方法，利用化学自组装技术将胰高血糖素的抗体组装到ＳＰＲ基片上，首先通过已知浓度的胰高血糖素进行ＳＰＲ检测，确定了其结合常数，并以此对未知浓度的胰高血糖素进行了测定，样品无需纯化和标记。     

Insulin trigger, cyclic AMP-dependent activation and phosphorylation of a plasma membrane cyclic AMP phosphodiesterase

Regulation of blood glucose levels by the liver is primarily achieved by the action of two peptide hormones, insulin and glucagon, which bind to specific receptors associated with the hepatocyte plasma membrane. Whilst the molecular action of glucagon at the level of the cell plasma membrane in activating adenylate cyclase is relatively well understood, we know little, if anything, of the molecular consequences of insulin occupying its receptor. We demonstrate here that insulin, at physiologically relevant concentrations, can trigger the cyclic AMP-dependent activation and phosphorylation of a low Km cyclic AMP phosphodiesterase attached to the liver plasma membrane. Such an effect may in part explain the ability of insulin to inhibit the increase in cellular cyclic AMP content that glucagon alone produces by activation of adenylate cyclase. Our observation that basal, intracellular cyclic AMP levels are insufficient to allow insulin to activate the cyclic AMP phosphodiesterase, yet those cyclic AMP levels achieved after exposure of the cells to glucagon are sufficient, gives a molecular rationale to Butcher and Sutherland's proposal that it is necessary to first elevate cellular cyclic AMP levels before they can be depressed by insulin.     

Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels

The endocrine part of the pancreas plays a central role in blood-glucose regulation. It is well established that an elevation of glucose concentration reduces secretion of the hyperglycaemia-associated hormone glucagon from pancreatic alpha 2 cells. The mechanisms involved, however, remain unknown. Electrophysiological studies have demonstrated that alpha 2 cells generate Ca2+-dependent action potentials. The frequency of these action potentials, which increases under conditions that stimulate glucagon release, is not affected by glucose or insulin. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system, and co-localizes with insulin in pancreatic beta cells. We now describe a mechanism whereby GABA, co-secreted with insulin from beta cells, may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABAA-receptor Cl- channels in alpha 2 cells. These observations provide a model for feedback regulation of glucagon release, which may be of significance for the understanding of the hypersecretion of glucagon frequently associated with diabetes.     

Abolition of the expression of inhibitory guanine nucleotide regulatory protein Gi activity in diabetes

Many cell-surface receptors for hormones appear to exert their effects on target cells by interacting with specific guanine nucleotide binding regulatory proteins (G-proteins) which couple receptors to their second-messenger signal generation systems. A common intracellular second messenger, which is used by many hormones, is cyclic AMP. This is produced by adenylate cyclase, whose activity is controlled by two G-proteins, Gs which mediates stimulatory effects and Gi inhibitory effects on adenylate cyclase activity. In liver, the hormone glucagon increases intracellular cAMP concentrations by activating adenylate cyclase by a Gs-mediated process. This effect of glucagon is antagonised by the hormone insulin, although the molecular mechanism by which insulin elicits its actions is obscure. However, insulin receptors exhibit a tyrosyl kinase activity and appear to interact with G-proteins, perhaps by causing phosphorylation of them. In type I diabetes, circulating insulin levels are abnormally low, giving rise to gross perturbations of metabolism as well as to a variety of complications such as ionic disturbances, neuropathies of the nervous system, respiratory and cardiovascular aberrations and predisposition to infection. We show here that experimentally-induced type I diabetes leads to the loss of expression of Gi in rat liver. As it has been suggested that Gi may couple receptors to K+-channels as well as mediating the inhibition of adenylate cyclase, aberrations in the control of expression of this key regulatory protein in type I diabetes may be expected to lead to pleiotropic effects.     

Glucagon stimulates the cardiac Ca2+ current by activation of adenylyl cyclase and inhibition of phosphodiesterase

Glucagon exerts positive inotropic and chronotropic effects in the heart. Like its glycogenolytic effect in liver cells, the cardiac effects of glucagon are often correlated with adenylyl cyclase stimulation. Therefore, cyclic AMP-dependent phosphorylation of L-type Ca2+ channels might be involved in the inotropic effect of glucagon. There have been no reports, however, of the effects of glucagon on the cardiac Ca2+ current (ICa). Also, the physiological effects of glucagon could involve mechanisms other than stimulation of adenylyl cyclase. Here we show that glucagon enhances ICa in frog and rat ventricular myocytes. The effect of glucagon in rats resulted from a stimulation of adenylyl cyclase. In frogs, however, the effect of glucagon on ICa was smaller and occurred at a concentration tenfold lower than in rats, and adenylyl cyclase was not modified. In addition, cAMP potentiated the effect of glucagon on ICa in frog ventricle, which correlated with the observed inhibition by glucagon of low-Km cAMP phosphodiesterase activity. Therefore, this is an example of a hormone that affects cardiac function in a similar way to a variety of synthetic cardiotonic compounds, such as milrinone and Ro-20-1724. Inhibition of phosphodiesterase activity by glucagon may be essential in animals in which glucagon increases cardiac contractility but does not effectively stimulate adenylyl cyclase.     

Lateral habenula as a source of negative reward signals in dopamine neurons

Midbrain dopamine neurons are key components of the brain's reward system, which is thought to guide reward-seeking behaviours. Although recent studies have shown how dopamine neurons respond to rewards and sensory stimuli predicting reward, it is unclear which parts of the brain provide dopamine neurons with signals necessary for these actions. Here we show that the primate lateral habenula, part of the structure called the epithalamus, is a major candidate for a source of negative reward-related signals in dopamine neurons. We recorded the activity of habenula neurons and dopamine neurons while rhesus monkeys were performing a visually guided saccade task with positionally biased reward outcomes. Many habenula neurons were excited by a no-reward-predicting target and inhibited by a reward-predicting target. In contrast, dopamine neurons were excited and inhibited by reward-predicting and no-reward-predicting targets, respectively. Each time the rewarded and unrewarded positions were reversed, both habenula and dopamine neurons reversed their responses as the bias in saccade latency reversed. In unrewarded trials, the excitation of habenula neurons started earlier than the inhibition of dopamine neurons. Furthermore, weak electrical stimulation of the lateral habenula elicited strong inhibitions in dopamine neurons. These results suggest that the inhibitory input from the lateral habenula plays an important role in determining the reward-related activity of dopamine neurons.     

葛根芩连汤及其聚集物颗粒对STZ诱导 2型糖尿病大鼠的降糖作用研究

葛根芩连汤是中药经典名方,在临床应用中显示出良好的治疗糖尿病的效果.研究观察高速离心分离的汤药聚集物颗粒组分(沉淀)、溶质组分(上清)在高脂高糖饮食(4周)后注射链脲佐菌素诱导的2型糖尿病模型Wistar大鼠上的降糖作用,测量体重、空腹血糖,血脂、血浆胰岛素、多脏器SOD活力,阐析该汤剂降糖降脂功效与其聚集物颗粒的关系.由实验得出,葛根芩连汤中的聚集物颗粒组分(沉淀)具有抗糖尿病活性,且此种活性可能经由提升胰腺和肝脏抗氧化能力、促进胰岛素分泌和改善血脂代谢而达成.     

Effects of breakfast with different calorigenic amounts on blood glucose, insulin and glucagon levels

This study was aimed to investigate the relationship between breakfast and serum glucose, insulin and glucagon concentrations in order to establish a model breakfast appropriate for Chinese. Twenty-four volunteers were randomly assigned to four study groups: high carbohydrate breakfast, high fat and protein breakfast, the typical breakfast and fasting. Each subject had serum and urine samples collected while fasting and at 1,2 and 3.5 hours following the meal. The concentration of serum glucose, insulin and glucagon was measured. The levels of serum glucose in group A, B and C differed significantly at 1 and 2 hour after meal compared to those at fasting (P<0.05). The serum glucose in group A increased insignificantly after meal. The serum insulin levels were in group A, B and C significant different compared with control group(P<0.05).Those peaked at 1 hour after meal, with group C rising the furthest. Compared with the fasting group, the serum glucagons rose and maintained the increase after breakfast in group A, B and C (P<0.05). The data suggested that various diets with different calorigenic amounts increased hormone concentration to various extents. We found that a breakfast rich in carbohydrates could maintain proper blood glucose level.     

Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells

Antagonistic activities of glucagon and insulin control metabolism in mammals, and disruption of this balance underlies diabetes pathogenesis. Insulin-producing cells (IPCs) in the brain of insects such as Drosophila also regulate serum glucose, but it remains unclear whether insulin is the sole hormonal regulator of glucose homeostasis and whether mechanisms of glucose-sensing and response in IPCs resemble those in pancreatic islets. Here we show, by targeted cell ablation, that Drosophila corpora cardiaca (CC) cells of the ring gland are also essential for larval glucose homeostasis. Unlike IPCs, CC cells express Drosophila cognates of sulphonylurea receptor (Sur) and potassium channel (Ir), proteins that comprise ATP-sensitive potassium channels regulating hormone secretion by islets and other mammalian glucose-sensing cells. They also produce adipokinetic hormone, a polypeptide with glucagon-like functions. Glucose regulation by CC cells is impaired by exposure to sulphonylureas, drugs that target the Sur subunit. Furthermore, ubiquitous expression of an akh transgene reverses the effect of CC ablation on serum glucose. Thus, Drosophila CC cells are crucial regulators of glucose homeostasis and they use glucose-sensing and response mechanisms similar to islet cells.