Voxel-based analyses of magnetization transfer imaging of the brain in hepatic encephalopathy

AIM: To evaluate the spatial distribution of cerebral abnormalities in cirrhotic subjects with and without hepatic encephalopathy (HE) found with magnetization transfer imaging (MTI). METHODS: Nineteen cirrhotic patients graded from neurologically normal to HE grade 2 and 18 healthy control subjects underwent magnetic resonance imaging. They gave institutional-review-board-approved written consent. Magnetization transfer ratio (MTR) maps were generated from MTI. We tested for significant differences compared to the control group using statistical non-parametric mapping (SnPM) for a voxelbased evaluation. RESULTS: The MTR of grey and white matter was lower in subjects with more severe HE. Changes were found in patients with cirrhosis without neurological deficits in the basal ganglia and bilateral white matter. The loss in magnetization transfer increased in severity and spatial extent in patients with overt HE. Patients with HE grade 2 showed an MTR decrease in white and grey matter: the maximum loss of magnetization transfer effect was located in the basal ganglia [SnPM (pseudo-)t = 17.98, P = 0.0001]. CONCLUSION: The distribution of MTR changes in HE points to an early involvement of basal ganglia and white matter in HE.     

Beneficial effects of sub-chronic activation of glucagon-like peptide-1 (GLP-1) receptors on deterioration of glucose homeostasis and insulin secretion in aging mice

Aging is associated with an increased incidence of glucose intolerance and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is an important insulinotropic peptide secreted from the gastrointestinal tract in response to nutrient absorption. The present study was designed to assess the sub-chronic glucose regulatory effects of the potent long-acting GLP-1 receptor agonist, (Val(8))GLP-1, in aging 45-49 week old mice. Daily injection of (Val(8))GLP-1 (25 n mol/kg body weight) for 12 days had no significant effect on food intake, body weight, non-fasting plasma glucose and insulin concentrations. However, after 12 days, the glycaemic response to intraperitoneal glucose was improved (P<0.05) in (Val(8))GLP-1 treated mice. In keeping with this, glucose-mediated insulin secretion was enhanced (P<0.05) and insulin sensitivity improved (P<0.05) compared to controls. These data indicate that sub-chronic activation of the GLP-1 receptor by daily treatment with (Val(8))GLP-1 counters aspects of the age-related impairment of pancreatic beta-cell function and insulin sensitivity.     

Ethanol in human brain by magnetic resonance spectroscopy: correlation with blood and breath levels, relaxation, and magnetization transfer

BACKGROUND: Proton magnetic resonance spectroscopy (1H MRS) allows measurement of alcohol in the human brain after alcohol consumption. However, the quantity of alcohol that can be detected in the brain by 1H MRS pulse sequences has been controversial, with values ranging from about 24% to 94% of the temporally concordant blood alcohol concentrations. The quantitation of brain alcohol is critically affected by the kinetics of alcohol uptake and elimination, by the relaxation times of the protons that give rise to the brain alcohol signal, and by the specifics of both pulse sequence timing and radio frequency pulse applications. METHODS: We investigated these factors in 20 light-drinking subjects after oral administration of approximately 0.85 g/kg body weight of alcohol by localized 1H MRS and measurements of blood and breath alcohol concentrations obtained at the same time. Specifically, we measured transverse and longitudinal relaxation times of brain alcohol and its signal saturation on application of on- or off-resonance radio frequency pulses. All 1H MRS measurements were performed at a time after brain and blood alcohol concentrations had equilibrated. RESULTS: 1H MRS measures of brain alcohol were correlated highly with both breath and blood alcohol concentrations after equilibration in brain tissue. The measured 1H MRS relaxation times of brain alcohol were shorter than given in previous reports that were limited by smaller subject numbers, improper use of 1H MRS methods, and estimates rather than measurements. The brain alcohol signal decreased by about 30% on application of on- or off-resonance saturation pulses. CONCLUSIONS: 1H MRS allows direct measurement of brain alcohol, formerly only possible indirectly through inferences from breath alcohol levels. Quantitation of brain alcohol levels need to take into account measured relaxation times and alcohol signal attenuation due to presence and timing of standard radio frequency MRS pulses. Saturation experiments give evidence for the existence of more than one compartment of brain alcohol characterized by different molecular environments. They suggest that a fraction of brain alcohol is invisible to 1H MRS.     

Elevated serum levels of visfatin in gestational diabetes: a comparative study across various degrees of glucose tolerance

Aims/hypothesis Concentrations of visfatin are increased in insulin-resistant conditions, but the relationship between visfatin and insulin and/or insulin resistance indices in pregnancy remains unclear. Insulin resistance in pregnancy is further accentuated in women with gestational diabetes mellitus (GDM). Thus we assessed serum levels of visfatin in pregnant women with varying degrees of glucose tolerance. Materials and methods Fasting visfatin levels were measured at 28 weeks of gestation in 51 women divided according to their response to a 50-g glucose challenge test (GCT) and a 75-g OGTT: control subjects (n = 20) had normal responses to both a GCT and an OGTT; the intermediate group (IG; n = 15) had a false-positive GCT, but a normal OGTT; the GDM group (n = 16) had abnormal GCTs and OGTTs. Results There were no age or BMI differences between analysed groups. Across the subgroups there was a progressive increase in glucose and insulin at 120 min of the OGTT (p < 0.01). This was accompanied by an increase in visfatin, from 76.8 ± 14.1 ng/ml in the control subjects, to 84.0 ± 14.7 ng/ml in the IG group and 93.1 ± 12.3 ng/ml in the GDM group (p < 0.01 for GDM vs control subjects). There was a positive correlation between visfatin and fasting insulin (r = 0.38, p = 0.007) and insulin at 120 min of the OGTT (r = 0.39, p = 0.006). Conclusions/interpretation An increase in fasting visfatin, the levels of which correlate with both fasting and post-glucose-load insulin concentrations, accompanies worsening glucose tolerance in the third trimester of pregnancy. However, the significance of these findings, and in particular the role of visfatin in the regulation of insulin sensitivity during pregnancy, remains to be elucidated. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. G. M. Prelevic and H. S. Randeva are both senior authors.     

Triglycerides and glucose index as an insulin resistance marker in a sample of healthy adults

AimTo assess the association between elevated triglycerides/glucose index (TGI) and insulin resistance (IR) or hyperinsulinemia after oral glucose tolerance test (OGTT) in a sample of healthy adults.MethodsWe conducted an analytical cross-sectional study in euthyroid non-diabetic adults, who attended the outpatient service of a private clinic in Lima-Peru during the 2012–2016 period. Participants were categorized in two groups according to the presence or absence of elevated TGI, IR or hyperinsulinemia after OGTT. A TGI value ≥ 8.65 was considered as elevated. We defined IR as a Homeostasis Model Assessment (HOMA-IR) value ≥ 2.28 and hyperinsulinemia after OGTT as a serum insulin value ≥ 80μU/mL after 120 min of 75-g glucose intake. We elaborated crude and adjusted Poisson regression models to assess the association between elevated TGI and IR or hyperinsulinemia after OGTT. The reported association measure was the prevalence ratio (PR) with their respective 95% confidence intervals (95%CI).ResultsWe analyzed 118 individuals, the average age was 37.5 ± 11.3 years, 21 (17.8%) were males and the median BMI was 22.7 ± 1.6 kg/m². The prevalence of elevated TGI was 25.4% (n=30) while the prevalence of IR and hyperinsulinemia after OGTT was 24.6% (n=29) and 17.0% (n=20) respectively. In the adjusted model, elevated TGI was associated with both IR (aPR=6.36; 95%CI: 3.41–11.86) and hyperinsulinemia after OGTT (aPR=4.19; 95%CI: 1.81–9.70).ConclusionsWe found that elevated TGI was associated with both IR markers in a sample of euthyroid adults without T2DM and with a normal BMI. The simplicity of the TGI calculation makes it the first-choice alternative when the hyperinsulinemic-euglycemic clamp or HOMA-IR are not available.     

Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study

Dietary restriction (DR) retards aging and extends the maximum lifespan of laboratory mice and rats. To determine whether DR has similar actions in a primate species, we initiated a study in 1989 to investigate the effects of a 30% DR in 30 adult male rhesus monkeys. In 1994, an additional 30 females and 16 males were added to the study. Although the animals are still middle-aged, a few differences have developed between the control and DR animals suggesting that DR may induce physiologic changes in the rhesus monkey similar to those observed in rodents. Fasting basal insulin and glucose concentrations are lower in DR compared to control animals while insulin sensitivity is higher in the restricted animals. DR has also altered circulating LDL in a manner that may inhibit atherogenesis. These results suggest that DR may be slowing some age-related physiologic changes. In addition to measures of glucose and lipid metabolism, the animals are evaluated annually for body composition, energy expenditure, physical activity, hematologic indices, and blood or urinary hormone concentrations. In the next few years, the first animals will reach the average lifespan (26 years) of captive rhesus monkeys and it will become possible to determine if DR retards the aging process and extends the lifespan in a primate species.     

Plasma insulin is removed by hemodialysis: evaluation of the relation between plasma insulin and glucose by using a dialysate with or without glucose

The aim of the present study was to evaluate the alteration in plasma immunoreactive insulin (IRI) and glucose concentrations due to hemodialysis (HD) treatment by using a dialysate with or without glucose in HD patients. We divided the patients into three groups: non-diabetic patients (n-DM group), well-controlled diabetic patients (HbA(1c) <7.0% [w-DM group]), and poorly-controlled diabetic patients (HbA(1c) > or = 7.0% [p-DM group]). Using a dialysate with a glucose concentration of 100 mg/dL (glu(+)-dialysate) and a glucose-free dialysate (glu(-)-dialysate), we studied the daily profiles of plasma glucose in the three groups. We measured the levels of plasma glucose and IRI at three time points (predialysis and 2 h and 4 h after the initiation of dialysis) at pre(A) and postdialyzer (V) sites in HD patients. There was a significant increase in the daily profiles of the plasma glucose level from the time before dinner until bedtime in both the w-DM and p-DM groups, when comparing the values on an HD day with those on a non-HD day. In the p-DM group, the use of the glu(-)-dialysate resulted in a significant hyperglycemia in the evening hours when compared with the use of the glu(+)-dialysate. In the DM group, the use of the glu(+)-dialysate resulted in a significant decrease in the plasma glucose and IRI levels during HD. However, in the n-DM group, there was no difference in the plasma glucose levels during HD. On the other hand, the use of a glucose-free dialysate led to a significant decrease in the plasma glucose and IRI levels during HD in all groups. The plasma IRI levels decreased significantly between the A and V sites at each point in all groups irrespective of the glucose concentration of the dialysate. The present study confirmed that the concentration of not only glucose but also IRI had decreased during the passage of the plasma through the dialyzer. In HD patients with diabetes, the glucose content of the hemodialysis solution plays an important role in preventing acute hypoglycemia and hyperglycemia on HD days.     

In vivo chemical exchange saturation transfer imaging allows early detection of a therapeutic response in glioblastoma

Glioblastoma multiforme (GBM), which account for more than 50% of all gliomas, is among the deadliest of all human cancers. Given the dismal prognosis of GBM, it would be advantageous to identify early biomarkers of a response to therapy to avoid continuing ineffective treatments and to initiate other therapeutic strategies. The present in vivo longitudinal study in an orthotopic mouse model demonstrates quantitative assessment of early treatment response during short-term chemotherapy with temozolomide (TMZ) by amide proton transfer (APT) imaging. In a GBM line, only one course of TMZ (3 d exposure and 4 d rest) at a dose of 80 mg/kg resulted in substantial reduction in APT signal compared with untreated control animals, in which the APT signal continued to increase. Although there were no detectable differences in tumor volume, cell density, or apoptosis rate between groups, levels of Ki67 (index of cell proliferation) were substantially reduced in treated tumors. In another TMZ-resistant GBM line, the APT signal and levels of Ki67 increased despite the same course of TMZ treatment. As metabolite changes are known to occur early in the time course of chemotherapy and precede morphologic changes, these results suggest that the APT signal in glioma may be a useful functional biomarker of treatment response or degree of tumor progression. Thus, APT imaging may serve as a sensitive biomarker of early treatment response and could potentially replace invasive biopsies to provide a definitive diagnosis. This would have a major impact on the clinical management of patients with glioma.Glioblastoma multiformes (GBMs) account for more than 50% of all gliomas, and are among the deadliest of all human cancers. Approximately 10,000 patients in the United States are diagnosed each year with GBM, and the median survival time remains at 15 mo despite recent advances in surgery, radiation therapy, and chemotherapy (1). During the past two decades, our knowledge of the aberrant molecular mechanisms that underlie gliomas has increased extensively (2); however, advancement in the treatment of glioma has lagged far behind that in other cancers, except for significant progress made by the introduction of temozolomide (TMZ) (3, 4). TMZ, an oral alkylating chemotherapeutic agent, disturbs DNA replication and induces apoptosis of cancer cells, and subsequently arrests progression of the tumor. For these reasons, TMZ has been widely adopted as standard-of-care treatment for GBM (1, 5). Although TMZ can significantly prolong survival on average, only 45% of patients with newly diagnosed GBM gain substantial benefits from TMZ (6). Furthermore, even in cases in which the tumor responds well to initial treatment and appears to have disappeared on follow-up, recurrence is common and fatal in the middle of treatment or 1–2 y after completion of the treatment in most cases (7, 8).The prognosis and management is vastly different depending on whether one observes tumor progression or treatment effects. Thus, it is critical to decide whether the treatment should be continued or switched to avoid continuing ineffective treatments. Currently, management decisions in all phases of diagnosis, treatment and follow-up rely on MRI (9–11). Generally, clinicians make a decision based on interpretation of signal changes in T2-weighted (T2W) or fluid-attenuated inversion recovery and gadolinium enhancement on T1-weighted (T1W) imaging from one time point to another, typically covering several months. In addition, patients are taken back to the operating room for a repeat craniotomy and biopsy to make the confirmative diagnosis, as the currently available imaging methods often do not suffice to make the final decision. Thus, overall, there is an urgent need for the development of novel imaging techniques that can differentiate between continued progression vs. a positive response to therapy at these critical decision points as early and accurate as possible.Chemical exchange transfer (CEST) has drawn considerable attention as a novel mechanism of MRI contrast. This method provides more detailed physiological and functional information than conventional MRI and has emerged in the field of molecular imaging (12, 13). CEST contrast is achieved by applying a presaturation pulse at the resonance frequency of a slow–intermediate exchanging proton site (−NH, −OH, or metal-bound water molecule) of endogenous or exogenous agents. The resulting saturated or partially saturated spin is transferred to bulk water via chemical exchange. Consequently, specific molecular information is obtained indirectly through the MRI signal of tissue water. The net effect of CEST is to reduce the bulk water signal intensity detected in an imaging experiment, thereby providing negative contrast (14).Amide proton transfer (APT) imaging is one subset of CEST imaging that refers specifically to chemical exchange between protons of free tissue water (bulk water) and amide groups (−NH) of endogenous mobile proteins and peptides. It has been reported that such exchangeable protons are more abundant in tumor tissues than in healthy tissues (15). When applied to rats implanted with 9L gliosarcoma tumors in brain, APT imaging was able to distinguish between pathology-confirmed regions of tumor vs. tissue edema, whereas standard T1W, T2W, and fluid-attenuated inversion recovery imaging or diffusion-weighted imaging could not. Other previous reports demonstrated that the APT signal increased by 3–4% in tumor compared with peritumoral brain tissue in an experimental rat glial tumor at 4.7 T (16) and human brain tumor at 3 T (17). We recently demonstrated that APT imaging can distinguish histopathological World Health Organization grade of diffuse gliomas in patients (18). The mean APT signal increased with tumor grade (grade II, 2.1 ± 0.4%; III, 3.2 ± 0.9%; and IV, 4.1 ± 1.0%) and clearly discriminated between low-grade (i.e., grade II) and high-grade (i.e., grades III and IV) gliomas. Moreover, Zhou et al. clearly demonstrated in rat models that the method could distinguish tumor from radiation necrosis and further that the APT signal decreased in the tumor after radiation therapy (19). These previous studies indicate that APT imaging may be a more sensitive and specific biomarker for characterization of tumor grade or therapeutic response to radiation in brain tumors than other more conventional MRI methods.Here, we demonstrate quantitative assessment of early treatment response in short-term chemotherapy with TMZ in vivo by APT imaging of brain gliomas. A validated noninvasive biomarker of progression or therapeutic response of glioblastoma in patients could potentially reduce the need for craniotomy and biopsy during and after chemotherapy in these patients. Among the imaging methods that potentially can be used for this purpose, APT imaging appears to be a most promising method for early detection of a therapeutic response.     

Interrelationship of the rs7903146 TCF7L2 gene variant with measures of glucose metabolism and adiposity: The NEO study

Background and aims

We investigated the interrelationship of rs7903146-T in TCF7L2 with measures of glucose metabolism and measures of adiposity.

葡萄糖钳夹技术在糖尿病研究中的应用

本文介绍葡萄糖钳夹技术在糖尿病研究中的应用。通过葡萄糖钳夹技术可研究在正常或高血糖情况下机体的胰岛素敏感性，胰岛素分泌和葡萄糖，脂类和蛋白质代谢等变化。     

Associations between sarcopenia and white matter alterations in older adults with diabetes mellitus: A diffusion tensor imaging study

Aims/IntroductionOlder adults with diabetes mellitus are susceptible to sarcopenia. Diffusion tensor imaging studies have also shown that patients with diabetes have altered white matter integrity. However, the relationship between these structural changes in white matter and sarcopenia remains poorly understood.Materials and MethodsThe study included 284 older patients (aged ≥65 years) who visited the Tokyo Metropolitan Geriatric Hospital Frailty Clinic. We used diffusion tensor imaging to measure fractional anisotropy (FA) and mean diffusivity (MD) to evaluate changes in white matter integrity. We investigated the associations between sarcopenia, or its diagnostic components, and FA or MD in seven white matter tracts considered to be associated with sarcopenia according to the patients’ diabetes status.ResultsWe found significantly low FA or high MD values in the bilateral anterior thalamic radiations (ATR) and right inferior fronto‐occipital fasciculus (IFOF) of patients with Asian Working Group for Sarcopenia 2019‐defined sarcopenia, in all patients and those with diabetes. Using binominal regression analyses, we associated low FA values in the left ATR and right IFOF with sarcopenia in all patients and those with diabetes, after adjusting for age, gender, HbA1c, blood pressure, cognitive function, physical activity, depression, nutritional status, and inflammation.ConclusionsWhite matter alterations in left ATR and right IFOF are associated with the prevalence of sarcopenia in patients with diabetes. Specific changes to the left ATR and right IFOF tracts could play critical roles in the occurrence of sarcopenia in patients with diabetes.     

Data-driven classification of health status of older adults with diabetes: The diabetes and aging study

Background

We set out to identify empirically-derived health status classes of older adults with diabetes based on clusters of comorbid conditions which are associated with future complications.

Methods

We conducted a cohort study among 105,786 older (≥65 years of age) adults with type 2 diabetes enrolled in an integrated healthcare delivery system. We used latent class analysis of 19 baseline comorbidities to derive health status classes and then compared incident complication rates (events per 100 person-years) by health status class during 5 years of follow-up. Complications included infections, hyperglycemic events, hypoglycemic events, microvascular events, cardiovascular events, and all-cause mortality.

Results

Three health status classes were identified: Class 1 (58% of the cohort) had the lowest prevalence of most baseline comorbidities, Class 2 (22%) had the highest prevalence of obesity, arthritis, and depression, and Class 3 (20%) had the highest prevalence of cardiovascular conditions. The risk for incident complications was highest for Class 3, intermediate for Class 2 and lowest for Class 1. For example, the age, sex and race-adjusted rates for cardiovascular events (per 100 person-years) for Class 3, Class 2 and Class 1 were 6.5, 2.3, and 1.6, respectively; 2.1, 1.2, 0.7 for hypoglycemia; and 8.0, 3.8, and 2.3 for mortality.

Conclusions

Three health status classes of older adults with diabetes were identified based on prevalent comorbidities and were associated with marked differences in risk of complications. These health status classes can inform population health management and guide the individualization of diabetes care.     

Longitudinal brain magnetic resonance imaging study of the alcohol-preferring rat. Part I: adult brain growth

BACKGROUND: The alcohol-preferring (P) rat, a Wistar strain selectively bred to consume large amounts of alcohol voluntarily, has been used as an animal model of human alcoholism for 3 decades. Heretofore, knowledge about brain morphology has been confined to postmortem examination. Quantitative neuroimaging procedures make it feasible to examine the potential longitudinal effects of alcohol exposure in vivo, while controlling modifying factors, such as age, nutrition, and exercise. To date, few imaging studies have considered what morphological changes occur with age in the rodent brain, and none has systematically applied quantitative neuroimaging approaches to measure volume changes in regional brain structures over extended periods in the adult rat. METHODS: We used structural magnetic resonance imaging (MRI) in a longitudinal design to examine 2 cohorts of adult P rats, never exposed to alcohol: Cohort A included 8 rats, 7 of which survived the entire study (578 days) and 4 MRI sessions; Cohort B included 9 rats, all of which survived the study (452 days) and 5 MRI sessions. RESULTS: Growth in whole-brain volume reached maximal levels by about 450 days of age, whereas body weight continued its gain without asymptote. Growth was not uniform across the brain structures measured. Over the initial 12 months of the study, the corpus callosum area expanded 36%, cerebellum 17%, and hippocampus 10%, whereas ventricle size was unchanged. Factors affecting growth rate estimates included litter effects, MR image signal-to-noise ratio, and measurement error. CONCLUSION: Unlike longitudinal human reports of regional volume declines in aging brain tissue, several brain structures in adult rats continued growing, and some growth patterns were litter-dependent. Determining normal regional growth patterns of brain and of the substantial variance exerted by litter differences, even in selectively bred rats, is essential for establishing baselines against which normal and aberrant dynamic changes can be detected in animal models of aging and disease.     

18F-FDG PET/CT分子显像评价缺血性心脏病患者心功能受损与脑葡萄糖代谢的相关性研究

目的从细胞能量代谢的角度评价缺血性心脏病(IHD)患者左心室功能受损与脑葡萄糖代谢水平之间的关系,探索心功能受损患者脑葡萄糖代谢减低的功能区。方法入选于2016年4月至2017年10月在北京安贞医院行99Tcm-甲氧基异丁基异腈(MIBI)门控单光子发射计算机断层扫描/CT(SPECT/CT)心肌灌注显像、18F-脱氧葡萄糖(FDG)门控正电子发射计算机断层成像/CT(PET/CT)心肌葡萄糖代谢显像和脑葡萄糖代谢显像(于3 d内完成所有检查)的IHD患者110例。采用QGS软件分析门控SPECT/CT心肌灌注显像和门控PET/CT心肌葡萄糖代谢显像数据,获取左心室功能参数,包括舒张末期容积(EDV)、收缩末期容积参数(ESV)和左心室射血分数(LVEF)。采用17段-5分法判断心肌存活和心肌梗死,并计算心肌存活范围及心肌梗死范围。根据心肌存活范围将患者分为存活心肌<10%组(44例)、存活心肌10%~<20%组(36例)和存活心肌≥20%组(30例)。采用Pearson相关系数分析心肌存活范围及心肌梗死范围等影像参数与脑葡萄糖代谢水平之间的相关性。采用脑代谢定量分析软件SPM评估全脑葡萄糖代谢标准摄取值的平均值(SUVmean)与小脑葡萄糖代谢SUVmean,并计算靶本比值全脑/小脑(TBR全脑/小脑),即全脑葡萄糖代谢SUVmean与小脑葡萄糖代谢SUVmean的比值。采用SPM软件评估3组之间不同脑功能区脑葡萄糖代谢水平的差异。结果男性101例,年龄(57±10)岁。TBR全脑/小脑与存活心肌范围、梗死心肌范围、门控SPECT/CT及门控PET/CT测得的LVEF有相关性(r值分别为0.280、-0.329、0.188、0.215,P均<0.05)。存活心肌<10%组患者的TBR全脑/小脑为(1.25±0.97),明显低于存活心肌10%~<20%组的1.32±0.17(P<0.05)和存活心肌≥20%组的1.34±0.16(P<0.05)。SPM分析发现,与存活心肌≥20%组比较,存活心肌<10%组患者的楔前叶、额叶、中央后回、顶叶、颞叶等脑功能区的脑葡萄糖代谢水平明显减低。结论IHD患者的左心室功能受损与脑葡萄糖代谢水平存在相关性。心肌存活量少的IHD患者,全脑葡萄糖代谢水平减低,且主要集中在与认知功能相关的脑功能区。     

β-抑制素在糖脂代谢中作用的研究进展

β-抑制素(β-arrestins)参与胰岛素信号通路,影响外周胰岛素的抵抗,还影响了胰岛素的分泌及脂代谢等.探讨β-arrestins调控的信号通路是深入研究胰岛素抵抗及胰岛素分泌的发病机制,可有望作为糖尿病治疗的重要靶点.

Abstract：

β-arrestins are involved in the insulin signaling pathway, affecting peripheral insulin resistance,also affecting insulin secretion and lipid metabolism. To clarify β-arrestins mediated signaling pathways is an approach to the pathogenesis and effective treatment of diabetes.     

Adiponectin in human pregnancy: implications for regulation of glucose and lipid metabolism

Aims/hypothesis Adiponectin is upregulated during adipogenesis and downregulated in insulin-resistant states. The mechanism(s) governing the re-arrangements from adipogenesis to facilitated lipolysis during pregnancy are unknown. Our purpose was to analyse the role of adiponectin relative to the metabolic changes in human pregnancy.Subjects, materials and methods Lean women (BMI <25 kg/m²) were evaluated longitudinally before conception, and in early (12–14 weeks) and late (34–36 weeks) pregnancy. Insulin sensitivity was measured using the glucose clamp technique. Venous blood and subcutaneous adipose tissue biopsies were obtained at each time point.Results Adiponectin concentrations were lower in the third trimester than in the pregravid condition (9.9±1.4 vs 13.5±1.8 μg/ml). The hypoadiponectinaemia was reflected by a 2.5-fold decrease in white adipose tissue adiponectin mRNA. These changes were associated with a 25% increase in fat mass (23.7±2.9 vs 18.9±2.9 kg). Insulin infusion decreased high molecular weight adiponectin complexes in pregravid women (9.9±0.6 vs 6.2±0.06) and the suppressive effect of insulin was lost during pregnancy. The pregnancy-mediated changes in adiponectin were strongly correlated with basal insulin levels and insulin sensitivity (p<0.0001). The relationship between adiponectin and insulin sensitivity was related to the decreased insulin regulation of glucose utilisation (r=0.55, p<0.001) but not of endogenous hepatic glucose production.Conclusions/interpretation These data demonstrate that pregnancy is associated with adiponectin changes in lean women. Hypoadiponectinaemia is reflected by a lower amount of high molecular weight adiponectin and by the ratio of high to low molecular weight multimers. The adiponectin changes relate to decreased insulin sensitivity of glucose disposal rather than alterations of lipid metabolism.     

The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study

GeroScience - Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects...