Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats

Mitochondrial dysfunction in adipose tissue may contribute to obesity‐related metabolic derangements such as type 2 diabetes mellitus (T2DM). Because mitochondria are a target for melatonin action, the goal of this study was to investigate the effects of melatonin on mitochondrial function in white (WAT) and beige inguinal adipose tissue of Zücker diabetic fatty (ZDF) rats, a model of obesity‐related T2DM. In this experimental model, melatonin reduces obesity and improves the metabolic profile. At 6 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control (C‐ZDF and C‐ZL) and treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk (M‐ZDF and M‐ZL). After the treatment period, animals were sacrificed, tissues dissected, and mitochondrial function assessed in isolated organelles. Melatonin increased the respiratory control ratio (RCR) in mitochondria from white fat of both lean (by 26.5%, P < 0.01) and obese (by 34.5%, P < 0.01) rats mainly through a reduction of proton leaking component of respiration (state 4) (28% decrease in ZL, P < 0.01 and 35% in ZDF, P < 0.01). However, melatonin treatment lowered the RCR in beige mitochondria of both lean (by 7%, P < 0.05) and obese (by 13%, P < 0.05) rats by maintaining high rates of uncoupled respiration. Melatonin also lowered mitochondrial oxidative status by reducing nitrite levels and by increasing superoxide dismutase activity. Moreover, melatonin treatment also caused a profound inhibition of Ca‐induced opening of mPTP in isolated mitochondria from both types of fat, white and beige, in both lean and obese rats. These results demonstrate that chronic oral melatonin improves mitochondrial respiration and reduces the oxidative status and susceptibility to apoptosis in white and beige adipocytes. These melatonin effects help to prevent mitochondrial dysfunction and thereby to improve obesity‐related metabolic disorders such as diabetes and dyslipidemia of ZDF rats.     

Beneficial effects of melatonin on obesity and lipid profile in young Zucker diabetic fatty rats

Abstract: The study objective was to investigate the effects of melatonin on obesity and obesity‐associated systolic hypertension and dyslipidemia in young male Zucker diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome. ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups (n = 10): naive (N), vehicle‐treated (V), and melatonin‐treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Melatonin reduced mean weight gain (51 ± 2/100 g BW) versus N‐ZDF group (58 ± 3, P < 0.05) without food intake differences. M‐ZDF rats showed an apparent reduction in systolic hypertension that proved not to be statistically significant, and a significant improvement in dyslipidemia, with a reduction in hypertriglyceridemia from 580 ± 40 to 420.6 ± 40.9 mg/dL (P < 0.01). Melatonin raised high‐density‐lipoprotein (HDL) cholesterol in ZDF (from 81.6 ± 4.9 to 103.1 ± 4.5 mg/dL, P < 0.01) and ZL rats (from 62.8 ± 4.8 to 73.5 ± 4.8 mg/dL, P < 0.05) and significantly reduced low‐density‐lipoprotein (LDL) cholesterol in ZDF rats from 5.20 ± 0.4 to 4.14 ± 0.3 mg/dL (P < 0.05) but had no effect on total cholesterol levels. To our knowledge, this is the first evidence of a positive effect of melatonin on overweight and lipid pattern of obese Zucker diabetic rats, supporting the proposition that melatonin administration may ameliorate overweight and lipid metabolism in humans. Because these benefits occurred in youth, before advanced metabolic and vascular complications, melatonin might help to prevent cardiovascular disease associated with obesity and dyslipidemia.     

不同糖代谢痛风患者β细胞功能及代谢特征分析

目的 探讨痛风患者从正常糖耐量(NGT)到糖尿病不同糖代谢状态时的胰岛素抵抗与胰岛β细胞功能的演变,分析痛风合并糖代谢紊乱患者的代谢特征.方法 96例痛风患者分为糖耐量正常(NGT)组(n=35)、糖调节受损(IGR)组(n=27)及糖尿病组(n=34).测量身高、体重、血压,测定空腹血糖、空腹胰岛素、HbA1C、血清尿酸、总胆固醇、甘油三酯及C反应蛋白(CRP),计算体重指数(BMI)、稳态模型评估的胰岛素抵抗指数(HOMA-IR)、稳态模型评估的胰岛β细胞功能指数(HOMA-B)和胰岛素敏感指数(ISI).结果 糖尿病组和IGR组的BMI、餐后2h血糖(2hPG)、空腹胰岛素、HbA1C、总胆固醇、甘油三酯、CRP、HOMA-IR均高于NGT组(P<0.05或P<0.01),而糖尿病组及IGR组ISI均低于NGT组(0.023±0.018和0.024±0.017对0.052±0.026,P<0.05).NGT组、IGR组和糖尿病组HOMA-B差异有统计学意义(87.6±25.1、126.46±34.2及173.75±32.1,P<0.05).糖尿病组糖尿病家族史阳性率高于NGT组(41.17%对11.4%,P<0.05).logistic回归分析显示,年龄、BMI、收缩压、甘油三酯、CRP、ISI与糖尿病独立相关,而尿酸与糖尿病无相关性.结论 重度胰岛素抵抗、胰岛β细胞分泌功能障碍、BMI增加、C反应蛋白水平增高、脂代谢异常、遗传易感性是痛风患者合并糖尿病的主要代谢特征.     

Thermal, but not mechanical, nociceptive behavior is altered in the Zucker Diabetic Fatty rat and is independent of glycemic status.

This study investigated the possible link between developing hyperglycemia and mechanical and/or thermal hyperalgesia in the Zucker Diabetic Fatty (ZDF) rat. When normoglycemic (nonfasting blood glucose levels of 6 mM), 6-week-old ZDF rats were glucose intolerant compared to the nondiabetic Zucker lean control (ZL) rats, but there was no difference in their response to a noxious mechanical (paw pressure test) or thermal (hot plate) stimulus (mechanical nociceptive thresholds: ZDF 176.7+/-14.4 g, ZL 161.7+/-13.3 g; latencies to response to the thermal stimulus: ZDF 13.1+/-1.6 sec, ZL 16.7+/-1.5 sec). Blood glucose levels in untreated ZDF rats increased to 28.4+/-2.9 mM by 20 weeks of age, while ZDF rats treated with the insulin sensitizer, rosiglitazone, and ZL rats remained normoglycemic (< or =8 mM) throughout the study. Hyperglycaemia in ZDF rats was not associated with mechanical hyperalgesia, as the nociceptive threshold remained constant in both the rosiglitazone-treated and untreated ZDF rats and in the ZL rats throughout the study. In contrast, the latency to response to the thermal stimulus increased with time in ZL rats, but remained constant in hyperglycaemic ZDF rats such that the difference reached significance by 9 weeks of age (ZDF 11.6+/-1.7 sec, ZL 21.8+/-2.7 sec, p<0.01) and is consistent with hyperalgesia in the ZDF phenotype. However, this difference was not moderated by maintaining normoglycaemia in rosiglitazone-treated ZDF rats (12.8+/-1.3 sec). Together, the data suggest that hyperglycemia does not play a central role in the development of hyperalgesia in the ZDF rat.     

Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats

Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Identification of brown fat (beige/brite) in white adipose tissue (WAT) prompted us to investigate whether melatonin is a brown‐fat inducer. We used Zücker diabetic fatty (ZDF) rats, a model of obesity‐related type 2 diabetes and a strain in which melatonin reduces obesity and improves their metabolic profiles. At 5 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control and those treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk. Melatonin induced browning of inguinal WAT in both ZDF and ZL rats. Hematoxylin–eosin staining showed patches of brown‐like adipocytes in inguinal WAT in ZDF rats and also increased the amounts in ZL animals. Inguinal skin temperature was similar in untreated lean and obese rats. Melatonin increased inguinal temperature by 1.36 ± 0.02°C in ZL and by 0.55 ± 0.04°C in ZDF rats and sensitized the thermogenic effect of acute cold exposure in both groups. Melatonin increased the amounts of thermogenic proteins, uncoupling protein 1 (UCP1) (by ~2‐fold, P < 0.01) and PGC‐1α (by 25%, P < 0.05) in extracts from beige inguinal areas in ZL rats. Melatonin also induced measurable amounts of UCP1 and stimulated by ~2‐fold the levels of PGC‐1α in ZDF animals. Locomotor activity and circulating irisin levels were not affected by melatonin. These results demonstrate that chronic oral melatonin drives WAT into a brown‐fat‐like function in ZDF rats. This may contribute to melatonin′s control of body weight and its metabolic benefits.     

胰岛素强化治疗对初诊2型糖尿病患者胰岛β细胞功能和胰岛素抵抗的影响

目的探讨阶梯式胰岛素强化治疗对初诊2型糖尿病（T2DM）患者胰岛β细胞功能和胰岛素抵抗（IR）的影响及机制。方法初诊T2DM患者61例,进行为期2周的胰岛素强化治疗和后续10周的预混胰岛素治疗,比较治疗前后FPG、2hPG、HbA1c、Fins、2hIns、FC-P、2hC-P、TC、TG、胰岛β细胞分泌指数（HOMA-β）和胰岛素抵抗指数（HOMA-IR）的变化。结果治疗后患者FPG、2hPG、HbA1 c和HOMA-IR显著下降,而Fins、2hIns、FC-P、2hC-P和HOMA-β显著上升。结论对血糖明显升高的初诊T2DM患者,短期胰岛素强化治疗及后续数周预混胰岛素皮下注射治疗可有效控制血糖,明显改善胰岛8细胞功能并减轻IR。     

不同糖化血红蛋白水平的2型糖尿病患者血浆皮质醇水平及临床意义

目的探讨不同糖化血红蛋白(HbA1c)水平的2型糖尿病(T2DM)患者血清皮质醇水平与血糖、胰岛素抵抗的相关性。方法选取2019年3月—2020年5月期间在该院检测过皮质醇的T2DM患者106例,分为HbA1c≤7%。7%组和HbA1c>7%组。对比分析两组患者的血清皮质醇(8:00)水平的差异以及其与空腹血糖(FBG)、HbA1c、HOMA指数(HOMA-IR)之间的相关性。结果HbA1c>7%组的血清皮质醇(8:00)、FBG、HbAlc及HOMA-IR水平显著高于HbA1c≤7%组,差异有统计学意义(P<0.05);全部T2DM患者血清皮质醇(8:00)水平与FBG、HbA1c呈正相关(P<0.05)。结论T2DM患者存在血清皮质醇(8:00)水平增高,且皮质醇分泌过高的程度与患者血糖水平的高低密切相关,可将血浆皮质醇作为血糖控制情况的评价指标之一。     

Mineralocorticoids,glucose homeostasis and type 2 diabetes mellitus: The Henan Rural Cohort study

AimsWe aimed to evaluate the associations of mineralocorticoids with type 2 diabetes mellitus (T2DM) and glucose homeostasis among rural Chinese adults.MethodsA total of 2713 participants were selected from the Henan Rural Cohort study. Serum mineralocorticoids were measured by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were employed to evaluate the associations of mineralocorticoids with pre-diabetes and T2DM. Linear regression was implemented to assess the associations of aldosterone and 11-deoxycorticosterone with different markers of glucose homeostasis by different diabetes status.ResultsElevated aldosterone and 11-deoxycorticosterone were associated with an increased prevalence of pre-diabetes and T2DM (P < 0.05), with a nonlinear dose-response trend, but the association between 11-deoxycorticosterone and T2DM was no statistical significance after adjustment. A 100% increase in ln-aldosterone was associated with a 0.029 mg/dl higher fasting plasma glucose (FPG) and a 1.2% higher HOMA2-IR among those with normal glucose tolerance (NGT), and related to a 0.034 mg/dl lower FPG, a 1.1% higher HbA1c and a 1.3% higher HOMA2-β among individuals with pre-diabetes. A 100% increment in ln-11-deoxycorticosterone was associated with a 16% increase in HbA1c and a 5.6% decrease in HOMA2-β in participants with T2DM.ConclusionsHigher aldosterone and 11-deoxycorticosterone are associated with T2DM risk and glucose homeostasis disorder among different diabetes status.     

Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats

Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M‐ZDF and M‐ZL) or vehicle as control groups (C‐ZDF and C‐ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C‐ZDF in comparison with C‐ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic‐induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M‐ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity.     

利用Botnia钳夹试验评估新HOMA稳态模型

目的 研究新HOMA稳态模型(HOMA2)的胰岛素敏感性指数(HOMA2-%S)和分泌功能指数(HOMA2-%B)在临床中的应用价值.方法 利用80例重庆地区多囊卵巢综合征妇女[正常糖耐量(NGT)组50人,糖调节受损(IGR)组30人]的口服葡萄糖耐量试验和Botnia钳夹试验资料,应用传统HOMA稳态模型(HOMA1)计算胰岛素敏感性指数HOMAl-ISI、分泌功能指数HOMA1-β和葡萄糖处置指数DI-HOMA1,借助新HOMA稳态模型计算胰岛素敏感性指数HOMA2-%S、分泌功能指数HOMA2-%B和葡萄糖处置指数DI-HOMA2,分别研究两种敏感性指数(HOMAl-ISI和HOMA2-%S)与Botnia钳夹试验稳态葡萄糖输注速率(GIR)的相关性,以及两种分泌功能指数(HOMA1-β和HOMA2-%B)与第一时相胰岛素分泌(AIR)的相关性.结果 HOMA2-%S与GIR的Pearson线性相关系数为0.503(P相似文献   

非酒精性脂肪性肝病并发2型糖尿病患者血尿酸水平变化及其临床意义

目的 探讨非酒精性脂肪性肝病(NAFLD)并发2型糖尿病(T2DM)患者血尿酸(SUA)水平变化及其临床意义。方法 2015年6月～2019年12月我院收治NAFLD患者316例,其中并发T2DM患者218例,未并发T2DM患者98例,采用单因素和多因素Logistic回归分析确定与T2DM发生相关的独立危险因素。结果 并发T2DM组男性比例显著高于非T2DM组(59.6%对42.9%,P<0.05),体质指数(BMI)为(27.2±2.9)kg/m²,显著高于非T2DM组,糖化血红蛋白(HbA1C)水平为(9.2±2.1)%,显著高于非T2DM组,血高密度脂蛋白(HDL)水平为(0.9±0.2)mmol/L,显著低于非T2DM组,甘油三酯(TG)水平为(1.9±0.5)mmol/L,显著高于非T2DM组,SUA水平为(335.8±72.6)μmol/L,显著高于非T2DM组,估算的肾小球滤过率(eGFR)为(158.4±40.6)ml/min/1.73m²,显著高于非T2DM组,空腹胰岛素(FINS)水平为(5.1±2.6)mIU/L,显著高于非T2DM组,胰岛素抵抗指数(HOMA-IR)为(1.9±1.1),显著高于非T2DM组;将性别、BMI、HbA1c、HDL、TG、SUA、eGFR、FINS和HOMA-IR作为自变量,将NAFLD患者是否并发T2DM作为因变量,纳入多因素Logistic回归分析,结果显示性别、HbA1c、SUA、FINS和HOMA-IR是NAFLD并发T2DM的独立危险因素(P<0.05),而BMI、HDL、TG和eGFR并不是影响NAFLD并发T2DM的独立危险因素(P>0.05);根据不同SUA水平将其从低到高分为SUA-1、SUA-2和SUA-3组,结果在218例合并糖尿病患者中,3组人群糖尿病占比分别为21.5%、32.1%和46.3%,差异显著(P<0.05),在88例女性NAFLD并发2型糖尿病患者中,其占比分别为10.2%、28.4%和61.4%,也具有显著性差异(P<0.05),但在130例男性人群,其占比分别为29.2%、34.6%和36.2%,无显著性统计学差异(P>0.05)。结论 NAFLD患者存在一些并发T2DM的危险因素,SUA就是一个重要的指标。在早期识别和防止这些危险因素的发生,对降低人群糖尿病的发生率有极大的帮助,应引起临床的高度重视。     

2型糖尿病及酮症患者血浆丝氨酸蛋白酶抵制剂水平变化及相关因素分析

目的 探讨初诊2型糖尿病(T2DM)及酮症(T2DK)患者血浆丝氨酸蛋白酶抵制剂(Vaspin)水平变化与BMI、血脂、血糖、胰岛素抵抗指数(HOMA-IR)等的关系.方法 采用ELISA法测定28例T2DM患者、32例T2DK患者及25例正常人(NC组)血浆Vaspin水平,分析血浆Vaspin水平与BMI、血脂、血糖和HOMA-IR等的关系.结果 T2DM组血浆Vaspin水平明显高于NC组[(0.71±0.18 )μg/L vs (0.52±0.13 )μg/L,P＜0.05],T2DK组又明显高于T2DM组[(1.95±0.21)μg/L vs (0.71±0.18)μg/L,P＜0.01].空腹血浆Vaspin水平分别与BMI、三酰甘油(TG)、空腹血糖(FPG)、糖化血红蛋白(HbA1c)和HOMA-IR呈明显正相关(P＜0.05),与Fins和胰岛素分泌指数(HOMA-IS)呈明显负相关(P＜0.05).BMI、FPG和HOMA-IR是影响血浆Vaspin水平的独立相关因素.结论 血浆Vaspin水平的改变与糖脂代谢紊乱和胰岛素抵抗有关,并可能参与了T2DM及T2DK的发生和发展.     

非酒精性脂肪性肝病合并2型糖尿病患者血清抵抗素和黄醇结合蛋白4水平及其临床意义探讨

目的 探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)血清抵抗素和黄醇结合蛋白4(RBP4)水平变化及其临床意义。方法 2017年10月～2021年1月我院诊治的NAFLD合并T2DM患者106例和NAFLD患者106例,检测空腹血糖(FBG),采用化学发光法检测空腹胰岛素(FINS)水平,计算HOMA-β指数和胰岛素抵抗指数(HOMA-IR),采用ELISA法检测血清抵抗素、RBP4、肿瘤坏死因子(TNF-α)和白介素(IL-6)水平。结果 合并T2DM患者血清TC和HDL-C水平分别为(4.7±0.5)mmol/L和(1.1±0.2)mmol/L,显著低于NAFLD患者【分别为(5.6±0.6)mmol/L和(1.4±0.3)mmol/L,P<0.05】;合并T2DM患者血清GGT水平(102.3±15.5)U/L,显著高于NAFLD患者【(71.6±4.6),P<0.05】,而两组血清ALT、AST和ALP水平无显著性差异(P>0.05);合并T2DM患者血清FBG、FINS和HOMA-IR水平分别为(7.7±0.8)mmol/L、(6.7±1.2...     

大黄酸改善糖尿病大鼠空腹血糖、胰岛素敏感性并增强肝脏PPARγ和GLUT-2的表达

目的 探讨大黄酸改善高脂喂养联合链脲佐菌素(STZ)诱导糖尿病大鼠血糖及肝脏胰岛素敏感性的作用及其可能机制.方法 (1)55只雄性Wistar大鼠随机分为正常对照组(NC,n=15)和糖尿病组(DM,n=40).NC组以基础饲料喂养,DM组以高脂饲料喂养5周后给予一次性腹腔注射STZ(30ms/kg),其中30只成模大鼠再分为糖尿病模型组(DM-C)和糖尿病大黄酸治疗组(DM-T),后者即开始大黄酸灌胃(100 mg·kg-1·d-1),灌胃11周后处死动物,收集标本,记录体重、肝重,测定空腹血糖(FBG)、甘油三酯(TG)、总胆同醇(TC)、HbA1C、糖化血清蛋白(GSP)等生化指标,放射免疫法测定血清胰岛素浓度(FINS),计算胰岛素敏感指数(ISI)及稳态模型评估的胰岛素抵抗指数(HOMA-IR).(2)免疫组化法检测肝脏组织中PPARγ的表达,Western印迹法检测肝脏组织中葡萄糖转运蛋白2(GLUT-2)表达.结果 实验结束时,测得DM-C组FBG[(22.57±3.23 vs 7.11±1.44)mmoL/L,P<0.01]、TG[(0.89±0.29 vs 0.58±0.17)mmoL/L,P<0.01]、HbA1C[(12.49±1.96 138 8.36±0.84)%,P<0.01]、GSP[(57.29±4.14 vs13.43±2.70)μmol/L,P<0.01]和肿瘤坏死因子α[TNF-α,(1.365±0.133 vs 1.233±0.159)μg/L,P<0.05]较NC组均显著升高.DM-C组肝重指数亦明显高于NC组(0.032±0.004 vs 0.024±0.002,P<0.01),FINS与NC组无明显差别,ISI较NC组下降明显[In(ISI),-5.46±0.61 vs -4.81±0.75,P<0.05],HOMA-IR较NC组升高[In(HOMA-IR),2.34±0.64 vs 1.70±0.78,P<0.05].DM-C组肝脏PPARγ [11 131.7(5 723.1-18 979.4) vs 48 782.1(21 576.7-108 829.5),P<0.01]和GLUT-2(0.98±0.35vs 1.29±0.27,P<0.05)表达较NC组有明显下降趋势.而DM-T组大鼠的FBG[(15.94±3.16)mmol/L]、HbA1C[(10.51±1.74)%]和GSP[(47.31±6.09)μmol/L]、In(HOMA-IR)(1.86±0.30)等较DM-C组均显著降低(P<0.05或P<0.01),In(ISI)(-4.97±0.29)较DM-C组升高明显(P<0.05).肝脏PPARγ/[35 156.3(24 554.3-86 660.9)],GLUT-2(1.55±0.55)蛋白表达水平较DM-C组明显增强(P<0.05或P<0.01).结论 大黄酸可降低糖尿病大鼠血糖、HbA1C及GSP、改善糖尿病大鼠胰岛素敏感性,其机制可能与增强PPARγ、GLUT-2蛋白表达有关.     

Melatonin increases brown adipose tissue mass and function in Zücker diabetic fatty rats: implications for obesity control

Melatonin limits obesity in rodents without affecting food intake and activity, suggesting a thermogenic effect. Previously we demonstrated that melatonin browns subcutaneous fat in Zücker diabetic fatty (ZDF) rats. Other works pointed to melatonin as a signal that increases brown adipose tissue (BAT) mass and function in rodents. However, direct proof of thermogenic properties (uncoupled mitochondria) of the newly recruited BAT in response to melatonin is still lacking. Therefore, in this work, we investigated if melatonin recruits thermogenic BAT in ZDF rats. Zücker lean (ZL) and ZDF animals were subdivided into two groups, control (C) and treated with oral melatonin (M) for 6 weeks. Mitochondrial mass, activity of citrate synthase (CS), and respiratory chain complexes I and IV were lower in C‐ZDF than in C‐ZL animals (P < .001). Melatonin treatment increased BAT weight in ZDF rats (P < .001). Also, it rose mitochondrial mass (P < .01) and activities of CS and complexes I and IV (P < .001) in both, ZDF and ZL rats. Uncoupling protein 1 (UCP1) mRNA and protein were 50% lower in BAT from obese rats. Also, guanosine diphosphate (GDP) binding was lower in ZDF than in lean rats (P < .01). Melatonin treatment of obese rats restored the expression of UCP1 and GDP binding to levels of lean rats and sensitized the thermogenic response to cold exposure. These data demonstrated that melatonin recruits thermogenic BAT in ZDF rats. This may contribute to melatonin's control of body weight and its metabolic benefits.     

Peroxisome proliferator-activated receptor (PPAR)-alpha agonism prevents the onset of type 2 diabetes in Zucker diabetic fatty rats: A comparison with PPAR gamma agonism

Peroxisome proliferator-activated receptor (PPAR)-gamma agonists are insulin sensitizers, whereas PPAR alpha agonists are lipid-lowering agents in humans. Chronic treatment with PPAR gamma agonists has been shown to prevent the onset of diabetes in young Zucker diabetic fatty (ZDF) rats; however, the effects of PPAR alpha agonists have not been well characterized in this model. Here we investigated chronic efficacy of PPAR alpha and nonthiazolidinedione (nTZD) PPAR gamma agonists on the onset of diabetes in 6-wk-old male ZDF rats. Whereas treatment with the nTZD PPAR gamma agonist completely prevented development of hyperglycemia, PPAR alpha activation was associated with lowering of food intake and body weight and reductions in fed and fasting hyperglycemia, with prevention of the hyperinsulinemic peak preceding the development of hyperglycemia in ZDF rats. Both compounds improved glucose tolerance during an oral glucose tolerance test with concomitant increases in insulin response. Such improvements of insulin secretion were associated with increased islet to total pancreatic area ratio and pancreatic insulin contents. Hyperinsulinemic-euglycemic clamp studies demonstrated that nTZD PPAR gamma reduced basal endogenous glucose production and increased insulin-stimulated glucose disposal, consistent with an improved insulin action as a cause of the improved glucose homeostasis. In contrast, activation of PPAR alpha did not significantly improve glucose metabolism during the hyperinsulinemic-euglycemic clamp. In conclusion, chronic treatment of ZDF rats with a PPAR gamma agonist completely prevented the onset of diabetes by improving both insulin action and secretion, whereas PPAR alpha agonism was partially effective, primarily by improving the pancreatic islet insulin response. Unlike the PPAR gamma agonist, the PPAR alpha agonist demonstrated efficacy without inducing body weight gain and cardiomegaly. This study suggests a possible role for PPAR alpha agonists in the prevention of type 2 diabetes mellitus.     

利格列汀联合门冬胰岛素50治疗肝源性糖尿病患者疗效及HOMA-IR和HOMA-β水平变化

目的 观察应用利格列汀联合门冬胰岛素50治疗肝源性糖尿病患者的疗效及胰岛素抵抗指数(HOMA-IR)和胰岛β 细胞功能指数(HOMA-β)水平的变化.方法 2017年1月 ～2019年12月我院收治的98例非酒精性脂肪性肝病合并肝源性糖尿病患者被随机分为对照组49例和观察组49例,分别给予门冬胰岛素50或门冬胰岛素50...     

糖化血红蛋白与胰岛β细胞功能关系的研究

目的 探讨不同糖代谢状态糖化血红蛋白（HbA1c）与胰岛β细胞功能的关系.方法 选取2010年6月至2013年2月为评价糖耐量水平而来南京大学医学院鼓楼医院内分泌科就诊者913例,所有受试者均行75 g口服葡萄糖耐量试验（OGTT）及胰岛素释放试验,测定HbA1c,根据HbA1c水平将受试者分为HbA1c ＜5.7％（277例）、5.7％≤HbA1c≤6.4％（391例）及HbA1c＞6.4％组（245例）;根据OGTT结果分为正常糖耐量组（NGT,205例）,糖调节受损组（IGR,328例）及2型糖尿病组（T2DM,380例）.以1/稳态模型胰岛素抵抗指数（1/HOMA-IR）、Matsuda胰岛素敏感指数（ISIM）评价胰岛素敏感性,以处置指数DI（早时相DI30、总时相DI120）评估校正胰岛素敏感性之后的胰岛β细胞功能.多组计量资料间比较采用方差分析,分类计数资料采用卡方检验,胰岛功能相关指数在校正性别、年龄、BMI之后采用一般线性模型进行比较.结果 与HbA1c ＜5.7％组相比,5.7％≤HbA1c≤6.4％组的DI30、DI120、ISIM、1/HOMA-IR分别下降了39％、33％、13％、14％;HbA1c＞6.4％组的DI30、DI120、ISIM、1/HOMA-IR分别下降了68％、66％、21％、32％（F=12.765 ～ 317.316,均P＜0.05）.在正常糖耐量阶段的人群中,5.7％≤HbA1c≤6.4％组的DI30、DI120明显低于HbA1c＜5.7％组（F=4.516、4.215,P＜0.05）;在HbA1c＜ 5.7％的人群中,DI30及DI120按照NGT→ IGR→T2DM的方向下降（F =87.604、108.369,P＜0.05）.结论 胰岛β细胞功能的进行性衰退及胰岛素抵抗共同促进了HbA1 c的升高;HbA1c与血糖结合能够更好地反映个体胰岛功能情况.     

妊娠期糖尿病孕妇氧化三甲胺及其相关代谢产物与胰岛素抵抗和β细胞功能的相关性分析

目的:探讨妊娠期糖尿病（GDM）孕妇血清氧化三甲胺（TMAO）及其相关代谢产物与胰岛素抵抗（IR）和β细胞功能的相关性。方法:本研究为横断面研究。选取2010年10月至2012年8月天津市内六城区的GDM孕妇,收集其身高、体重,并计算其孕早期体重指数（BMI）;测量记录空腹血糖（FPG）、空腹胰岛素、TMAO及其相关代...