高血压性脑出血患者胰岛素抵抗的临床研究

目的:探讨高血压性脑出血(HIH)患者是否存在胰岛素抵抗(IR)与高胰岛紊血症(HIS),以及IR与患者病情、预后的关系。方法:测定了56例高血压性脑出血患者及37例原发性高血压患者、49例健康人的血糖(FPG)与血清胰岛素水平(FINS),同时采用胰岛素敏感性指数(ISI)方法进行计算,3个月后随访高血压性脑出血患者,进行日常生活能力(ADL)Barthel指数评分。结果:高血压性脑出血患者FPG及FINS增多明显高于对照组(P<0.001,P<0.001),其ISI较对照明显减低(P<0.001)。高血压性脑出血患者轻型组与重型组的FPG、FINS、ISI比较也存在显著性差异(P<0.001,P<0.05,P<0.001)。随访高血压性脑出血患者轻型组ADL评分明显高于重型组。结论:高血压性脑出血患者存在IR及HIS,其胰岛索水平及IR程度与患者病情、预后有关。建议对高血压性脑出血患者的血糖水平升高与IR及ISI下降者应积极使用改善胰岛素敏感性的药物治疗。     

胰岛素抵抗与脑卒中的关系探讨

目的 研究胰岛素抵抗（IR）与脑卒中之间的关系。方法 选取急性脑卒中患者作为研究对象,测定血糖（FPG）、胰岛素水平（FINS）、总胆固醇（CH）、甘油三酯（TG）,同时采用李光伟等提出的胰岛素敏感指数（ISI）方法进行计算。结果 急性脑卒中患者FINS显著高于对照组（P＜0．01）,其ISI较对照组显著降低（P＜0．01）。脑梗死组FINS显著高于脑出血组（P＜0．05）,其ISI较脑出血组显著降低（P＜0．05）。结论 急性脑卒中患者存在IR,IR为其重要的危险因素,尤其是脑梗死患者IR比脑出血患者更为敏感。     

颅脑损伤后血糖、胰岛素紊乱的相互关系及意义

目的：探讨颅脑损伤病人的血糖及胰岛素浓度及相互关系。方法：测定了71例颅脑损伤病人的血糖及胰岛素浓度部份病人进行糖耐量试验。结果：轻型组血糖及胰岛素含量均低于重型组（P＜0．01），血糖浓度与胰岛素浓度呈正相关（γ=0．784，P＜0．001）。糖耐量试验：1小时末，两组血糖与胰岛素含量均升高，但轻型组血糖低于重型组（P．＜0．001），胰岛素却高于重型组（P＜0．05）；2小时末，轻型组血糖及胰岛素均显著下降，而重型组则变化不大。结论：脑外伤后升高血糖因素虽是多方面的，但胰岛素含量的相对不足和绝对不足是高血糖的主要因素，为脑外伤后高血糖胰岛素治疗提供了理论依据。     

脑血管病与胰岛素抵抗的关系探讨

目的 研究胰岛素抵抗(IR)与脑卒中之问的关系。方法 选取急性脑卒中患作为研究对象，测定血糖(FPG)、胰岛素水平(FINS)、总胆固醇(CH)、甘油三酯(TG)，同时采用李光伟等提出的胰岛素敏感指数(ISI)方法进行计算。结果 急性脑卒中患FINS显高于对照组(P＜0.01)，其ISI较对照组显降低(P＜0．01)。脑梗死组FINS显高于脑出血组(P＜0．05)，其ISI较脑出血组显降低(P＜0．05)。结论 急性脑卒中患存在IR，IR为其重要的危险因素，尤其是脑梗死患IR比脑出血患更为敏感。     

胰岛素抵抗、血脂异常与急性脑梗死关系的初步研究

目的探讨胰岛素抵抗、血脂异常与急性脑梗死之间的关系.方法对45例急性脑梗死患者作空腹血糖(FPG)、血清胰岛素(FINS)及血脂测定,并与25例原发性高血压(EH)患者及25例健康体检者比较.采用李光伟提出的方法计算胰岛素敏感性指数(ISI)为空腹血清胰岛素与空腹血糖乘积的倒数,即1/(FINS×FPG),取其自然对数.结果急性脑梗死患者FINS明显高于两对照组(P＜0.01);胰岛素敏感性指数明显低于两健康对照组(P＜0.01);TG、CHOL、apoB明显高于健康对照组(P＜0.01),HDL明显低于对照组(P＜0.01).FPG、LDL及apoA1三组间无明显差异.结论急性脑梗死存在胰岛素抵抗,胰岛素抵抗和血脂异常可能在脑梗死的发生中起重要作用.胰岛素抵抗在脑梗死中的重要作用有待于进一步深入研究.     

高血压并脑梗死患者肿瘤坏死因子水平变化与胰岛素抵抗的关系

目的：为探讨高血压并脑梗死（HCI）患者血清肿瘤坏死因子－α（TNF－α）水平变化与胰岛素抵抗（IR）的关系。方法：采用氧化酶法、放免法和酶联免疫法分别测定23例HCI患者（A组）、25例高血压患者（B组）、21例正常健康人（C组）的空腹血糖（FBG）、空腹胰岛素（FINS）及血清TNF－α值，并计算胰岛素敏感指数（ISI）。结果：A组与B组、C组比较显示：FINS、TNF－α水平显著增高，而ISI显著降低。相关分析发现，TNF－α与ISI呈显著负相关，而与FINS呈显著正相关。结论：HCI患者TNF－α水平增高，且与胰岛素抵抗并存，可能参与高血压脑梗死的发生和发展。     

胰岛素抵抗、血脂异常与高血压合并脑梗死关系的研究

目的　研究胰岛素抵抗 (IR)、血脂异常与高血压合并脑梗死之间的关系。方法　测定 6 7例高血压合并脑梗死患者 (脑梗死组 33例 ,腔隙性脑梗死组 34例 )的血脂、血糖、血清胰岛素以及胰岛素敏感指数(ISI) ,并与 30名健康对照者进行比较。结果　高血压合并脑梗死患者血脂、血糖、胰岛素、ISI与对照组比较均有显著性差异 (均P <0 .0 1) ,其中腔隙性脑梗死组胰岛素明显高于脑梗死组 (P <0 .0 5 ) ,而ISI较脑梗死组明显减低 (P <0 .0 5 )。结论　高血压合并脑梗死存在IR ,IR可能是其独立危险因素之一。尤其腔隙性脑梗死可能与IR关系更密切     

脑梗死与胰岛素抵抗关系的实验研究

目的 对胰岛素抵抗与脑梗死之间的关系进行探讨。方法 分别对62例单纯性脑梗死患者和35例健康对照组进行空腹血糖(FBG)、空腹破岛素(FINs)、胆固醇(Tc)、甘油三酯(TG)，计算胰岛素敏感指数(ISI)，并与神经功能缺失评分和梗死灶面积进行直线相关分析。结果 脑梗死患者组FB6、FINS、TC、TG显著高于对照组(尸＜0．05)；ISI显著低于对照组。脑梗死轻型组与脑梗死重型组之间FINS和IsI也存在显著差异。IsI与梗死灶面积、神经功能缺失评分呈负相关。结论 破岛素抵抗与脑梗死有密切关系，可能是脑梗死的一个重要危险因素，它参与了脑梗死的发生发展。     

颅脑损伤后血糖,胰岛素紊乱的相互关系及意义

目的：探讨颅脑损伤病人的血糖及胰岛素浓度及相互关系。方法：测定了７１例颅脑损伤病人的血糖及胰岛素浓度部分病人进行糖耐量试验。结果：轻型组血糖及胰岛素含量均低于重型组（Ｐ〈０．０１），血糖浓度与纱浓度呈正相关（γ＝０．７８４，Ｐ〈０．００１）。糖耐量试验；１小时末，两组血糖与胰岛素含量均升高，但轻型组氏于重型组（Ｐ〈０．００１），胰岛素地高于重型组（Ｐ〈０．０５）；２小时末，轻型组血主胰岛素均显著下     

伴颈动脉粥样硬化的急性脑梗死患者胰岛素抵抗与TNF-α关系的临床研究

目的探讨肿瘤坏死因子α(TNF-α)与胰岛素抵抗(IR)在伴颈动脉粥样硬化(CAS)的急性脑梗死中的作用机制及二者之间的关系。方法比较44例伴CAS的急性脑梗死患者与80例健康对照组中空腹血糖(FPG)、空腹血清胰岛素(FINS)、胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR)、TNF-α、体重指数(BMI)等6个因素之间有无差异,并了解IR与TNF-α的相关性。结果伴CAS的急性脑梗死组与对照组相比,FPG、FINS、HOMA-IR、TNF-α明显高于对照组,ISI明显低于对照组(P<0.01或P<0.05);脑梗死组中,ISI与TNF-α呈显著负相关(r=-0.494,P<0.01)。结论在伴有CAS的急性脑梗死中同时存在IR及TNF-α升高,IR程度与TNF-α呈正相关。     

Insulin binding and fluid-phase endocytosis stimulation in the mouse neuroblastoma cell line 41A3

As well as many other hormones and growth factors, insulin is known to influence several processes in the CNS; its specific effects, however, are still poorly understood. Neuroblastoma cell lines represent a useful experimental system for the analysis of the insulin-specific effect on neurons, in the absence of possible regulatory mechanisms elicited by other neuronal/glial cells and/or soluble factors. The expression and the binding properties of insulin receptors, as well as the insulin effects on both membrane fluidity and cell surface architecture, have been investigated in 41A3 mouse neuroblastoma cells, respectively by radioligand-binding fluorescence spectroscopy and scanning electron microscopy. In the same cells, insulin-induced modifications on cytoskeletal organisation also have been studied.Binding studies were performed using ¹²⁵I-insulin, while the cationic fluorescent probe trimethylammonium 1,6-diphenyl-1,3,5-hexatriene was used for biophysical investigations.The results presented in this paper provide evidence that insulin interacts with 41A3 neuroblastoma cells through a receptor-mediated mechanism and that, in these cells, insulin binding modifies the cell surface morphology and stimulates endocytosis.     

Adult-level insulin binding is present in term fetal rat CNS membranes

Insulin binding was measured using partially-purified membranes prepared from the brains of term fetal and adult rats as the source of receptors. The membranes from the fetal rat brains bound at least as much insulin as did those from the adult rats at all concentrations of insulin used.This finding supports our hypothesis that insulin contributes to the postnatal growth of the rat brain.     

Exercise increases insulin signaling in the hippocampus: Physiological effects and pharmacological impact of intracerebroventricular insulin administration in mice

Increasing evidence indicates that physical exercise induces adaptations at the cellular, molecular, and systemic levels that positively affect the brain. Insulin plays important functional roles within the brain that are mediated by insulin‐receptor (IR) signaling. In the hippocampus, insulin improves synaptic plasticity, memory formation, and learning via direct modulation of GABAergic and glutamatergic receptors. Separately, physical exercise and central insulin administration exert relevant roles in cognitive function. We here use CF1 mice to investigate (i) the effects of voluntary exercise on hippocampal insulin signaling and memory performance and (ii) whether central insulin administration alters the effects of exercise on hippocampal insulin signaling and memory performance. Adult mice performed 30 days of voluntary exercise on running wheel and afterward both, sedentary and exercised groups, received intracerebroventricular (icv) injection of saline or insulin (0.5–5 mU). Memory performance was assessed using the inhibitory avoidance and water maze tasks. Hippocampal tissue was measured for [U‐¹⁴C] glucose oxidation and the immunocontent of insulin receptor/signaling (IR, pTyr, pAktser473). Additionally, the phosphorylation of the glutamate NMDA receptor NR2B subunit and the capacity of glutamate uptake were measured, and immunohistochemistry was used to determine glial reactivity. Exercise significantly increased insulin peripheral sensitivity, spatial learning, and hippocampal IR/pTyrIR/pAktser473 immunocontent. Glucose oxidation, glutamate uptake, and astrocyte number also increased relative to the sedentary group. In both memory tasks, 5 mU icv insulin produced amnesia but only in exercised animals. This amnesia was associated a rapid (15 min) and persistent (24 h) increase in hippocampal pNR2B immunocontent that paralleled the increase in glial reactivity. In conclusion, physical exercise thus increased hippocampal insulin signaling and improved water maze performance. Overstimulation of insulin signaling in exercised animals, however, via icv administration impaired behavioral performance. This effect was likely the result of aberrant phosphorylation of the NR2B subunit. © 2010 Wiley‐Liss, Inc.     

Ghrelin regulation of glucose metabolism

Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are implicated in the regulation of glucose metabolism via direct actions in the pancreatic islet, as well as peripheral insulin‐sensitive tissues and the brain. Although many studies have explored the role of ghrelin in glucose tolerance and insulin secretion, a complete mechanistic understanding remains to be clarified. This review highlights the local expression and function of ghrelin and GHSR1a in pancreatic islets and how this axis may modulate insulin secretion from pancreatic β‐cells. Additionally, we discuss the effect of ghrelin on in vivo glucose metabolism in rodents and humans, as well as the metabolic circumstances under which the action of ghrelin may predominate.     

胰岛素抗体和胰岛素抗性对脑梗死影响的临床研究

目的　为了探讨脑梗死 (CI)患者与胰岛素抗体 (IAb)及胰岛素抗性 (IR)的关系。方法　采用放射免疫法 ,测定 50例脑梗死与 30例脑动脉硬化 (AS)及正常对照组血浆IAb及IR。结果　CI及AS血浆IAb阳性率明显高于对照组 ,且脑梗死伴高血压者血浆IAb明显高于单纯脑梗死组。CI、AS患者存在明显胰岛素抵抗 ,且脑梗死伴高血压组与单纯脑梗死比较 ,其IR更明显。结论　IAb、IR参与了CI、AS的发病过程 ,IR可能是CI及AS的独立危险因素     

急性脑梗死与胰岛素抵抗及胰岛素抗体水平相关性分析

目的 探讨急性脑梗死(ACI)与胰岛素抵抗(IR)及胰岛素抗体(IAb)水平之间的相关性.方法 采用放射免疫法测定34例ACI组,28例ACI恢复期组及30名健康对照者的空腹血胰岛素(INS)、IAb水平,同时检测空腹血糖(FBG)、血脂,计算胰岛素敏感指数(ISI).结果 ACI组INS、IAb显著高于恢复期组及对照组;ISI较对照组显著降低.结论 ACI患者存在明显IR,血IAb水平亦显著增高,IR及IAb可能参与了ACI的发病过程.     

Developing rat brain binds monoiodinated insulin isomers similarly to other extrahepatic target tissues

We recently reported a series of binding and metabolic studies which led to the conclusion that the developing rat brain is a target tissue for insulin. Since insulin target tissues (extrahepatic) are capable of differentiating between various monoiodoinsulin isomers, we measured the binding of the B26 monoiodoinsulin isomer compared to the A14 in newborn rat brain preparations to determine if the developing rat brain shared the same relative binding of these isomers (viz. B26 >A14) with other extrahepatic tissues. The B26 isomer bound 1.57, 1.50 and 1.34 times as much as did the A14 to brain membranes, glia and neurons, respectively, whereas both isomers were bound equally by liver plasma membranes. Competition-inhibition curves were generated using homologous unlabeled (¹²⁷I) insulin isomers. Binding of the B26 isomer was greater than the A14 at all concentrations. Scatchard plots showed that the receptor concentrations for the two isomers were similar, and affinity profiles showed that the differences in binding could be accounted for by the greater affinity of the receptors for the B26 isomer. The results indicate that the developing rat brain shares with other extrahepatic insulin target tissues a greater affinity for B26 monoiodoinsulin isomer compared to A14. Future studies of insulin binding should avoid using mixtures of iodinated insulins that a uniform interpretation of data is made possible.     

血清胰岛素与急性脑血管病的关系

为了从临床上研究血清胰岛素对脑血管病的影响，选脑出血20例，脑梗塞44例，另选非脑血管病33例作为对照，对入院后次晨及出院前分别抽血查血清胰岛素及空腹血糖，结果：入院时血清胰岛素增高率脑出血组高于脑梗塞组及对照组（P＜0．001），脑梗塞治愈者中，入院时血清胰岛素增高者占多数（P＜0．05）．讨论：脑血管病急性期血清胰岛素增高与应激有关，胰岛素对缺血脑组织有重要的保护作用．     

Multiple system atrophy is associated with changes in peripheral insulin‐like growth factor system

Insulin‐like growth factors (IGF‐I and IGF‐II) have been shown to have several neurotrophic actions and IGF system may be impaired in neurodegenerative disorders. The aim of this study was to investigate the IGF system in patients with MSA and to evaluate correlations between this endocrine system and clinical features of the disease. Serum levels of IGF‐I, IGF‐II, insulin, IGF‐binding protein 1 (BP1), and IGF‐binding protein 3 (BP3) were measured in 25 patients with probable MSA and 25 age, sex and BMI‐matched healthy controls. Clinical status of each patient was evaluated with the Unified Multiple System Atrophy Rating Scale (UMSARS) Part II and the Hoehn and Yahr rating scale. IGF‐I levels were significantly higher in MSA (164.1 + 66.2 μg/L) than in healthy controls (111.7 + 60.3 μg/L; p = 0.001). Insulin levels were significantly higher in MSA patients (21.9 ± 14.4 μU/mL) than in healthy controls (13.3 ± 5.1 μU/mL, p = 0.048). No significant difference was found in serum IGF‐II, IGF‐BP1, and IGF‐ BP3 levels between patients with MSA and healthy controls. There was a trend toward significantly higher IGF‐II levels in MSA patients with UMSARS score <26 (1026.3 ± 442.6 μg/L) than MSA patients with UMSARS score >26 (796.1 ± 234 μg/L, p = 0.055). The results of this study demonstrated that IGF system is altered in MSA. The degenerative process in MSA could lead to a compensatory increase in IGF‐I and insulin in an attempt to provide additional support to degenerating neurons. © 2010 Movement Disorder Society.     

Insulin sensitivity in patients with anorexia nervosa and bulimia

Insulin sensitivity was studied using the euglycemic insulin clamp technique in 5 female patients with anorexia nervosa and 4 females with bulimia. The results were compared with those of 15 male patients with non-insulin-dependent diabetes mellitus. Euglycemic insulin clamp is performed for 2 h using the Biostator, during which time insulin was infused at a rate of 0.77 mU kg-1 min-1. Fasting plasma glucose and immunoreactive insulin tended to be lower in patients with anorexia nervosa than in those with bulimia (69.8 +/- 6.7 vs 75.9 +/- 7.7 mg/dl, and 5.9 +/- 2.0 vs 9.8 +/- 3.4 U/ml). The mean metabolic clearance rate (MCR) was 9.2 +/- 3.9 ml kg-1 min-1 for patients with anorexia nervosa, 5.1 +/- 2.2 ml kg-1 min-1 for patients with bulimia, and 3.8 +/- 0.3 ml kg-1 min-1 for patients with diabetes mellitus. However, one anorectic had a significantly high MCR. One anorectic and 3 bulimics had a significantly low MCR. These results suggest that insulin sensitivity varied in patients with anorexia nervosa, whereas it tended to decrease in some patients with bulimia but not to the same degree as in patients with diabetes mellitus.