Insulin increases macrophage triglyceride accumulation under diabetic conditions through the down regulation of hormone sensitive lipase and adipose triglyceride lipase

Diabetes mellitus (DM) is a major risk factor for the development of atherosclerosis, and high-serum levels of insulin are strongly associated with type 2 DM. Atherosclerosis is characterized by lipid-laden macrophage foam cell formations, which contain substantial amount of cholesterol and triglycerides (TG). This study analyzed for the first time, the effects of insulin on TG metabolism in macrophages under normal and diabetic conditions. Mouse peritoneal macrophages from C57BL6 mice were cultured under normal (5 mM) or high (diabetic condition, 25 mM) glucose concentration, with or without insulin, followed by the assessment of TGs metabolism in these cells. Under diabetic condition, insulin increased TG accumulation in macrophages by 100%, decreased cellular TG degradation by 21%, and increased C-reactive protein levels in macrophages by 83%. Insulin decreased hormone-sensitive lipase mRNA and protein expression by 28 and 60%, respectively, and adipose TG lipase (ATGL) protein expression by 36%, with no significant reduction in ATGL mRNA levels. The inhibition of insulin-mediated phosphorylation, and the addition of cyclic adenosine 3'5'-monoposphate, abolished the insulin-mediated inhibition of TGs degradation in cells. Insulin increases macrophage TGs accumulation only under diabetic conditions, suggesting that impaired glycemic control in diabetic patients treated with insulin may contribute to foam cell formations and enhanced inflammation in macrophages.     

Cord blood ASP is predicted by maternal lipids and correlates with fetal birth weight

Background: The acylation stimulating protein (ASP) is a potent lipogenic adipokine that correlates with postprandial triglyceride (TG) clearance and is linked to the pathophysiology of obesity and related disorders. Objective: To investigate ASP levels in cord blood and its relation to maternal and cord blood lipid parameters and fetal birth weight. Methods and Procedures: Thirty nondiabetic pregnant women, their newborns, and thirty‐three nonpregnant controls were included in this study. Fasting maternal and cord blood ASP, TGs, nonesterified fatty acids (NEFAs), cholesterol, glucose levels, in addition to maternal BMI and fetal birth weight were measured. Results: No significant difference was found between cord blood ASP (16.3 ± 0.96 nmol/l) and ASP levels in the adult controls (15.7 ± 1.0 nmol/l). Cord blood ASP, however, was lower than maternal plasma ASP levels (25.4 ± 1.6 nmol/l, P < 0.001). Yet, lipid levels in cord blood, particularly TGs were markedly decreased compared to control and maternal TG levels (threefold and 7.4‐fold, P < 0.001 respectively). Maternal TGs significantly correlated with fetal birth weight (r = 0.54, P = 0.002). Multiple regression analysis showed that maternal TGs (β = 0.57, P = 0.01) and NEFAs (β = 0.43, P = 0.024) predicted 45% variation in cord blood ASP levels, independent of all measured maternal and cord blood parameters. Cord blood ASP showed a positive correlation with fetal birth weight (r = 0.524, P = 0.037) in neonates above average fetal birth weight of the studied population. Discussion: This is the first study investigating ASP in cord blood. We suggest that maternal hypertriglyceridemia is associated with increased fetal ASP production, thus enhancing fetal fat storage independent of maternal glucose variations in nondiabetic women.     

糖尿病健康教育在糖尿病治疗中的效果分析

目的:为了提高糖尿病患者的糖尿病知识水平,从而增加患者对治疗的依从性。方法:对住院患者进行糖尿病教育,用同一份试卷分别于教育前后做出评估,并比较患者教育6个月前后的空腹血糖(FPG)、餐后2h血糖(2hPBs)、糖化血红蛋白(HbA1c)、胆固醇(TC)和甘油三酯(TG),并记录体重指数(BMI)、腰臀比。结果:(1)教育6个月后,患者参加教育后的自觉运动、控制饮食和糖尿病知识水平较教育前明显提高,差异有显著性(P<0.05)。(2)教育6个月后,体重指数(BMI)、腰臀比,空腹血糖(FPG)、餐后2h血糖(2hPBs)、糖化血红蛋白(HbA1c)、胆固醇(TC)和甘油三酯(TG)降低,差异有显著性(P<0.05)。结论:糖尿病教育对于预防和治疗糖尿病有非常重要的意义,患者参加教育后对治疗的依从性较教育前明显提高。     

老年2型糖尿病患者血清ANGPTL4、Betatrophin、Vaspin水平与血糖、血脂及下肢血管病变的关系研究

摘要 目的：探讨老年2型糖尿病（T2DM）患者血清脂肪因子血管生成素样蛋白4（ANGPTL4）、促代谢因子（Betatrophin）、腹腔脂肪型丝氨酸蛋白酶抑制剂（Vaspin）水平与血糖、血脂、下肢血管病变（LVD）的关系。方法：选取我院2018年8月～2019年8月收治的老年T2DM患者108例,根据患者是否合并LVD,分成LVD组（n=38）和无LVD组（n=70）,比较两组临床资料、血清ANGPTL4、Betatrophin、Vaspin水平、血糖指标[空腹血糖（FPG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）]、血脂指标[总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）]。经Pearson线性相关分析患者血清ANGPTL4、Betatrophin、Vaspin水平与血糖、血脂指标相关性。经Logistic多因素回归模型分析患者LVD发生的影响因素。结果：LVD组舒张压、收缩压均高于无LVD组（P＜0.05）。LVD组血清Betatrophin水平及TC、TG、LDL-C、FPG、2hPG、HbA1c高于无LVD组,血清ANGPTL4、Vaspin水平及HDL-C低于无LVD组（P＜0.05）。Pearson线性相关分析显示,血清ANGPTL4、Vaspin与TC、TG、LDL-C、FPG、2hPG、HbA1c呈负相关,与HDL-C呈正相关（P＜0.05）。血清Betatrophin与TC、TG、LDL-C、FPG、2hPG、HbA1c呈正相关,与HDL-C呈负相关（P＜0.05）。Logistic多因素回归模型分析结果显示,血清ANGPTL4、Betatrophin、Vaspin以及舒张压、TC、TG、HDL-C、LDL-C、FPG、2hPG、HbA1c是患者LVD发生的影响因素（P＜0.05）。结论：老年T2DM合并LVD患者的血清ANGPTL4、Vaspin水平明显下降,而血清Betatrophin水平升高,且三者与血糖、血脂指标均存在相关性,并且是患者发生LVD的影响因素,临床可考虑通过检测血清ANGPTL4、Betatrophin、Vaspin水平,辅助评估LVD的发生风险。     

Efficacy and safety of Touchi extract, an alpha-glucosidase inhibitor derived from fermented soybeans, in non-insulin-dependent diabetic mellitus

The water-extracted Touchi, a traditional Chinese food, exerted a strong inhibitory activity against rat intestinal alpha-glucosidase in foodstuffs. In borderline and developed diabetic subjects, 0.3 g of Touchi-extract (TE) significantly inhibited postprandial blood glucose levels. For confirmation of safety, 9 healthy subjects were given 1 g of TE before every meal (3 g/day) for 12 weeks. None indicated changes in hematological and relevant biochemical parameters, body weight or BMI. In a non-comparative study, 18 type-2 diabetic patients ingested 0.3 g of TE before every meal (0.9 g/day) for 6 months (mo). Blood glucose (mean; 9.31 +/- 0.71 mmol/L) and HbA(1c) (mean: 10.24 +/- 0.58%) levels gradually decreased, and significant effects were elicited on the blood glucose levels (8.61 +/- 0.66 mmol/L; p < 0.01) after 6 mo and HbA(1c) after 3 (9.13 +/- 0.43%; p < 0.05) and 6 mo (8.96 +/- 0.30%; p < 0.05) post-ingestion of TE. Indexes for serum lipids and total cholesterol level revealed moderate decreases with a slight increase in the high-density lipoprotein (HDL) level after TE ingestion. However, triglyceride (TG) levels significantly decreased at 3 (p < 0.05) and 6 mo (p < 0.01) post-ingestion of TE. In this study, other biochemical parameters were not affected in any of the patients, and no one complained of any side-effects or abdominal distension. TE, exhibiting alpha-glucosidase inhibitory activity, demonstrated an anti-hyperglycemic effect and may prove useful for improving glycemic control in patients suffering from non-insulin-dependent diabetic mellitus.     

孕期个性化营养干预对妊娠期糖尿病孕妇糖脂水平及妊娠结局的影响

目的:探讨孕期个性化营养干预对妊娠期糖尿病孕妇糖脂水平及妊娠结局的影响。方法:选择2016年8月-2017年10月期间于我院产检的妊娠期糖尿病孕妇160例,以随机数字表法分为研究组(n=80)和对照组(n=80)。对照组给予常规营养干预,研究组则予以孕期个性化营养干预。比较两组干预前后空腹血糖、餐后2h血糖、总胆固醇(TC)、三酰甘油(TG)、高密低脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,观察孕妇及新生儿并发症发生情况。结果:干预后两组孕妇空腹血糖、餐后2 h血糖显著降低,且研究组低于对照组(P0.05)。干预后对照组孕妇TC、TG、LDL-C较干预前显著升高(P0.05),HDL-C差异无统计学意义(P0.05),研究组血脂水平与干预前比较差异无统计学意义(P0.05),与对照组比较,研究组孕妇TC、TG、LDL-C水平更低(P0.05)。研究组妊娠期高血压、胎膜早破发生率均明显低于对照组(P0.05),两组感染、产后出血发生率比较无统计学差异(P0.05)。与对照组比较,研究组新生儿窘迫、巨大儿、新生儿低血糖、早产儿的发生率降低(P0.05)。结论:孕期个性化营养干预可有效改善妊娠期糖尿病孕妇的糖脂水平,且能够有效降低并发症发生率,从而改善妊娠结局。     

Postprandial leg uptake of triglyceride is greater in women than in men

The postprandial excursion of plasma triglyceride (TG) concentration is greater in men than in women. In this study, the disposition of dietary fat was examined in lean healthy men and women (n = 8/group) in either the overnight-fasted or fed (4.5 h after breakfast) states. A [14C]oleate tracer was incorporated into a test meal, providing 30% of total daily energy requirements. After ingestion of the test meal, measures of arteriovenous differences in TG and 14C across the leg were combined with needle biopsies of skeletal muscle and adipose tissue and respiratory gas collections to define the role of skeletal muscle in the clearance of dietary fat. The postprandial plasma TG and 14C tracer excursions were lower (P = 0.04) in women than in men in the overnight-fasted and fed states. Women, however, had significantly greater limb uptake of total TG compared with men on both the fasted (3,849 +/- 846 vs. 528 +/- 221 total micro mol over 6 h) and fed (4,847 +/- 979 vs. 1,571 +/- 334 total micromol over 6 h) days. This was also true for meal-derived 14C lipid uptake. 14C content of skeletal muscle tissue (micro Ci/g tissue) was significantly greater in women than in men 6 h after ingestion of the test meal. In contrast, 14C content of adipose tissue was not significantly different between men and women at 6 h. The main effect of nutritional state, fed vs. fasted, was to increase the postmeal glucose (P = 0.01) excursion (increase from baseline) and decrease the postmeal TG excursion (P = 0.02). These results support the notion that enhanced skeletal muscle clearance of lipoprotein TG in women contributes to their reduced postprandial TG excursion. Questions remain as to the mechanisms causing these sex-based differences in skeletal muscle TG uptake and metabolism. Furthermore, nutritional state can significantly impact postprandial metabolism in both men and women.     

格列美脲联合艾塞那肽治疗肥胖2型糖尿病的疗效观察

目的:探讨格列美脲联合艾塞那肽治疗肥胖2型糖尿病患者的临床效果。方法:选择2016年1月到2019年1月我院收治的82例肥胖2型糖尿病患者作为本次研究的对象,并将其随机的分为研究组和对照组,每组41例。研究组患者给予格列美脲联合艾塞那肽进行治疗,对照组患者给予格列美脲治疗,观察和比较两组患者治疗前后空腹血糖、餐后2 h血糖、空腹和餐后2 h血清C肽、身体质量指数(body mass index, BMI)、总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride, TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)和糖化血红蛋白(glycosylated hemoglobin, HbAlC)水平的变化。结果:治疗后,两组患者空腹血糖、餐后2 h血糖水平均较治疗前明显降低,餐后2 h血清C肽水平均较治疗前明显升高,且研究组以上指标的改善程度较对照组更明显(P0.05)。两组患者治疗前后空腹血清C肽水平比较差异无统计学意义(P0.05);治疗后,两组患者BMI、TC、TG、LDL-C和HbAlC水平均较治疗前显著降低,HDL-C水平明显升高,而研究组BMI、TC、TG、LDL-C和HbAlC水平显著低于对照组(P0.05),HDL-C水平明显高于对照组(P0.05)。结论:格列美脲片联合艾塞那肽治疗肥胖2型糖尿病可有效的控制患者血糖,降低BMI,改善血脂水平。     

Leptin responses to physical inactivity induced by simulated weightlessness

Physical inactivity induced by head-down bed rest (HDBR) affects body composition (BC). Leptin is involved in BC regulation by acting on fuel homeostasis. We investigated whether leptin and counterregulatory hormone levels are affected by a 7-day HDBR. Fasting blood was sampled daily (0700) in males (n = 8) and on alternating days in females (n = 8) for measurements of leptin, insulin, norepinephrine (NE), epinephrine (Epi), growth hormone (GH), cortisol, nonesterified fatty acid (NEFA), and glucose. BC was measured by H(2)(18)O dilution. Energy intake (men 10.5 +/- 0.2 MJ/day, women 7.9 +/- 0.3 MJ/day) and BC were unchanged by HDBR. Increased levels of leptin (men 40%, P = 0.003; women 20%, P = 0. 050), insulin (men 34%, P = 0.018; women 25%, P = 0.022), and the insulin-to-glucose ratio (men 30%, P = 0.049; women 25%, P = 0.031) were noted. GH, NE, Epi, and cortisol levels were unaltered. NEFA dropped in both sexes, but glucose decreased only in women. In conclusion, HDBR increased leptin levels independently of stress response, changes in fat mass, energy intake, or gender. These changes were correlated to the insulin-resistance development in men. Further analyses are required, but the results have to be considered for longer HDBR periods with 1) the well-described drop in energy intake and 2) the BC changes.     

Identification of a small molecule that stabilizes lipoprotein lipase in vitro and lowers triglycerides in vivo

Patients at increased cardiovascular risk commonly display high levels of plasma triglycerides (TGs), elevated LDL cholesterol, small dense LDL particles and low levels of HDL-cholesterol. Many remain at high risk even after successful statin therapy, presumably because TG levels remain high. Lipoprotein lipase (LPL) maintains TG homeostasis in blood by hydrolysis of TG-rich lipoproteins. Efficient clearance of TGs is accompanied by increased levels of HDL-cholesterol and decreased levels of small dense LDL. Given the central role of LPL in lipid metabolism we sought to find small molecules that could increase LPL activity and serve as starting points for drug development efforts against cardiovascular disease. Using a small molecule screening approach we have identified small molecules that can protect LPL from inactivation by the controller protein angiopoietin-like protein 4 during incubations in vitro. One of the selected compounds, 50F10, was directly shown to preserve the active homodimer structure of LPL, as demonstrated by heparin-Sepharose chromatography. On injection to hypertriglyceridemic apolipoprotein A-V deficient mice the compound ameliorated the postprandial response after an olive oil gavage. This is a potential lead compound for the development of drugs that could reduce the residual risk associated with elevated plasma TGs in dyslipidemia.     

血清HCY、MMP-9、NT-proBNP水平与老年2型糖尿病大血管病变的相关性研究

目的:探讨血清同型半胱氨酸(HCY)、金属蛋白酶9(MMP-9)、N-端B型钠利尿肽(NT-pro BNP)变化与老年2型糖尿病大血管病变的关系。方法:选取我院2014年5月至2016年5月收治的老年2型糖尿病患者50例,依据大血管病变发生情况将其分为合并大血管病变组(A组,n=25)和未合并大血管病变组(B组,n=25),另选取同期来我院进行体检的健康人员50例作为对照组,比较三组的一般临床资料、血清HCY、MMP-9、NT-pro BNP水平。结果:A组患者的收缩压、舒张压、空腹血糖(FBG)、餐后2h血糖(2h BG)水平均显著高于B组(P0.05),高密度脂蛋白胆固醇(HDL-C)水平显著低于B组(P0.05),但三组患者的性别、年龄、体质量指数(BMI)、糖化血红蛋白(Hb A1c)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平比较差异均无统计学意义(P0.05)。A组、B组患者的BMI、收缩压、舒张压、FBG、2h BG、Hb A1c、TG、TG、LDL-C水平均显著高于对照组(P0.05),LDL-C水平均显著低于对照组(P0.05),但三组人员的性别、年龄比较差异均无统计学意义(P0.05)。A组患者的血清HCY、MMP-9、NT-pro BNP水平均显著高于B组(P0.05);A组、B组患者的HCY、MMP-9、NT-pro BNP水平均显著高于对照组(P0.05)。结论:血清HCY、MMP-9、NT-pro BNP水平与老年2型糖尿病的大血管病变显著相关。     

西格列汀对早期2型糖尿病肾病患者肾功能的影响

目的:研究西格列汀对早期2型糖尿病肾病患者肾小球、肾小管标志性蛋白/酶的影响。方法:早期2型糖尿病肾病患者72例,随机数字表分为对照组36例、治疗组36例;两组均采用糖尿病饮食管理、运动治疗,在控制血糖、血脂、血压的基础上,治疗组给予磷酸西格列汀100 mg 1粒/次,1次/天,持续服药6月。观察治疗前、后两组血肌酐(Scr)、尿素氮(BUN)、糖化血红蛋白(Hb A1c)、血脂、空腹血糖(FBG)、餐后2小时血糖(2 h PBG)、血清胱抑素-C(Cys-C)及24 h尿微量白蛋白(24 h UAE)、尿N-乙酰-β-氨基葡萄糖苷酶(NAG)、尿β2-微球蛋白(β2-MG)的变化。结果:治疗后,治疗组血脂、Hb A1c、FBG、2 h PBG较对照组明显下降,差异有显著性(P0.05)。两组患者24 h UAE、NAG、β2-MG和Cys-C较治疗前均下降,差异有显著性(P0.05);两组治疗后相比,差异具有统计学意义(P0.05)。结论:西格列汀可以有效控制早期DN患者的血糖水平,减少血清Cys-C、尿微量白蛋白水平,减轻肾小管损伤,有利于延缓DN的病程和进展。     

Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats

The aim of the study was to evaluate blood glucose and lipid lowering effects of Umbelliferone (UMB) in streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180 to 200 g) were induced diabetes by administration of STZ (40 mg/kg) intraperitonially. Normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had increased plasma glucose and decreased insulin, total proteins (TP), and albumin in addition to decreased food intake and body weight. Elevation in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL), and reduction in high density lipoprotein cholesterol (HDL-C) in the plasma were observed. Liver and kidney tissues of diabetic rats had elevation in the levels of TC, TG, FFA, and PL. Treatment with UMB decreased plasma glucose and increased insulin, TP, and albumin apart from food intake and body weight. In UMB-treated diabetic rats, plasma and tissue TC, TG, PL and FFA, and plasma LDL-C, VLDL-C, and HDL-C reversed to near normal. Thus, reduction of blood glucose and lipid profiles indicates that UMB has antidiabetic and antihyperlipidemic effects in diabetic rats.     

Effects of acute sprint interval cycling and energy replacement on postprandial lipemia

High postprandial blood triglyceride (TG) levels increase cardiovascular disease risk. Exercise interventions may be effective in reducing postprandial blood TG. The purpose of this study was to determine the effects of sprint interval cycling (SIC), with and without replacement of the energy deficit, on postprandial lipemia. In a repeated-measures crossover design, six men and six women participated in three trials, each taking place over 2 days. On the evening of the first day of each trial, the participants either did SIC without replacing the energy deficit (Ex-Def), did SIC and replaced the energy deficit (Ex-Bal), or did not exercise (control). SIC was performed on a cycle ergometer and involved four 30-s all-out sprints with 4-min active recovery. In the morning of day 2, responses to a high-fat meal were measured. Venous blood samples were collected in the fasted state and at 0, 30, 60, 120, and 180 min postprandial. There was a trend toward a reduction with treatment in fasting TG (P = 0.068), but no significant treatment effect for fasting insulin, glucose, nonesterified fatty acids, or betahydroxybutryrate (P > 0.05). The postprandial area under the curve (mmol·l(-1)·3 h(-1)) TG response was significantly lower in Ex-Def (21%, P = 0.006) and Ex-Bal (10%, P = 0.044) than in control, and significantly lower in Ex-Def (12%, P = 0.032) than in Ex-Bal. There was no treatment effect (P > 0.05) observed for area under the curve responses of insulin, glucose, nonesterified fatty acids, or betahydroxybutryrate. SIC reduces postprandial lipemia, but the energy deficit alone does not fully explain the decrease observed.     

自然杀伤细胞对妊娠期糖尿病患者并发高脂血症的影响

目的：观察自然杀伤细胞（NK 细胞）对妊娠期糖尿病患者并发高脂血症的影响。方法：选择2013 年2月至2015 年4 月在我 院确诊的妊娠期糖尿病高脂血症患者95 例,作为研究组,同期选择体检健康孕妇100 例,作为对照组,对比两组的血糖、糖化血 红蛋白、身体质量指数（BMI）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、白 细胞介素-2（IL-2）、IL-6、干扰素-r（IFN-r）、NK 细胞及细胞亚型,并采用Person相关性分析NK细胞与血脂的相关性。结果：①研 究组空腹血糖、餐后2 h 血糖、糖化血红蛋白、BMI均明显高于对照组,差异具有统计学意义（P<0.05）;②研究组TC、TG、LDL-C 均明显高于对照组,HDL-C明显低于对照组,差异具有统计学意义（P<0.05）;③研究组IL-2、IFN-r明显低于对照组,差异具有统 计学意义（P<0.05）;IL-6 明显高于对照组,差异具有统计学意义（P<0.05）;④研究组的NK 细胞数量、CD4+/ CD3+、CD4+/ CD8+、 CD56++CD4+/ CD3+均低于对照组的（P<0.05）;CD8+/ CD3+、CD18+/ CD8+、CD19+/ CD3+均高于对照组的（P<0.05）;两组CD28+/ CD8+差异无统计学意义（P＞0.05）。⑤NK 细胞数量与TC、TG、LDL-C水平均呈负相关（r=-0.527、-0.598、-0.485）,NK 细胞数量与 HDL-C 水平呈正相关（r=0.528）。结论：NK 细胞在妊娠期糖尿病孕妇中数量减少,活性也降低,可能与参与免疫反应的NK细胞 不同表型细胞含量发生变化,导致血脂调节失衡,引发高血脂症的过程有关。     

Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in Type 2 diabetic patients

We evaluated the influence of chronic hypertriglyceridemia and endothelial dysfunction on myocardial glucose uptake (MGU) in Type 2 diabetic patients without coronary heart disease. Patients were divided into two groups according to fasting triglyceride (TG) levels: 5.4 +/- 1.1 and 1.5 +/- 0.3 mmol/l for high- and normal-TG groups, respectively. Five subjects were assigned to the high-TG group and 11 to the normal-TG group. Age, gender, body mass index, systolic and diastolic blood pressure, glucose, insulin, HbA1c, cholesterol, and HDL cholesterol were similar in the two groups, whereas free fatty acid (FFA) levels were higher in the high-TG group basally and at the end of the clamp. Furthermore, five healthy subjects were subjected to the same protocol and used as the control group. MGU was assessed by using 18F-labeled 2-fluoro-2-deoxy-D-glucose under hyperglycemic-hyperinsulinemic conditions. Basal endothelin-1 and nitric oxide levels were significantly higher in the high-TG group than in the normal-TG and control groups, and cGMP and maximal postischemic vasodilation were significantly decreased in the high-TG group compared with the normal-TG and control groups. However, significant alterations were found in the same parameters in the normal-TG group compared with the control group. By the end of the hyperglycemic clamp, in the high-TG group, MGU was approximately 40 and 65% of that in the normal-TG and control groups. MGU negatively correlated with TG, FFA, and endothelin-1, whereas a positive correlation was found with cGMP and maximal postischemic vasodilation. In conclusion, increased TG and FFA levels are risks, in addition to Type 2 diabetes mellitus, for myocardial insulin resistance, endothelial dysfunction, and alteration of nitric oxide/cGMP levels.     

Inhibition of intestinal bile acid transporter Slc10a2 improves triglyceride metabolism and normalizes elevated plasma glucose levels in mice

Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2-/- mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2-Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes.     

血清Fractalkine、Apelin水平与糖尿病视网膜病变患者血糖、血脂以及病程的关系研究

目的:研究血清Fractalkine(FKN)、爱帕琳肽(Apelin)水平与糖尿病视网膜病变(DR)患者血糖、血脂以及病程的关系。方法:选取我院于2015年1月至2016年12月收治的160例糖尿病患者为研究对象,行眼底荧光造影、裂隙灯显微镜检查,按照检查结果将其区分为非增生型DR组(稳定组,43例)、背景期DR组(背景组,62例)和增殖期DR组(增殖组,55例),另外于同期选取我院40例健康体检者为健康对照组(健康组),测量4组血清FKN、Apelin、空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)和总胆固醇(TC)水平,使用Pearson相关性分析分析血清FKN、Apelin与FPG、2hPG、HbA1c、HDL-C、LDL-C、TG、TC、糖尿病病程的相关性。结果:血清FKN、Apelin水平比较:增殖组背景组稳定组健康组,各组间比较差异具有统计学意义(P0.05);血清FPG、2hPG、HbA1c、LDL-C、TG、TC水平比较:增殖组背景组稳定组健康组,各组间比较差异具有统计学意义(P0.05);血清HDL-C水平比较:健康组稳定组背景组增殖组,各组间比较差异具有统计学意义(P0.05);采用Pearson相关性分析显示,血清FKN水平与FPG、2hPG、HbA1c、LDL-C、TG、TC、糖尿病病程呈正相关性(r=0.321、0.215、0.645、0.154、0.215、0.325、0.578,P0.05),与HDL-C呈负相关性(r=-0.547,P0.05);血清Apelin水平与FPG、2hPG、HbA1c、LDL-C、TG、TC、糖尿病病程呈正相关性(r=0.245、0.574、0.951、0.357、0.357、0.159、0.546,P0.05),与HDL-C呈负相关性(r=-0.459,P0.05);糖尿病病程、HbA1c、LDL-C、HDL-C、FKN和Apelin为DR病程的相关影响因素。结论:糖尿病伴发DR患者血清FKN、Apelin水平随着病程的加重逐渐增加,且这两种因子的水平与患者血糖、血脂代谢关系密切。