Effects of parathyroid hormone on cortical porosity,non-enzymatic glycation and bone tissue mechanics in rats with type 2 diabetes mellitus

Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats.Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75 μg/kg PTH (1–84) or vehicle 5 days per week over 12 weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence.Diabetes increased Ct.Po (vertebra (vert): + 40.6%, femur (fem): + 15.5% vs. ND group, p < 0.05) but had no effect on NEG. PTH therapy reduced vertebral NEG in the ND animals only (− 73% vs untreated group, p < 0.05), and increased femoral NEG in the DB vs. ND groups (+ 63%, p < 0.05). PTH therapy had no effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where reductions in vertebral maximum strain (− 22%) and toughness (− 42%) were observed in the DB vs. ND group (p < 0.05). PTH improved maximum strain in the vertebra of the ND animals (+ 21%, p < 0.05) but did not have an effect in the DB group. PTH increased femoral maximum strain (+ 21%) and toughness (+ 28%) in ND and decreased femoral maximum stress (− 13%) and toughness (− 27%) in the DB animals (treated vs. untreated, p < 0.05). Ct.Po correlated negatively with maximum stress (fem: R = − 0.35, p < 0.05, vert: R = − 0.57, p < 0.01), maximum strain (fem: R = − 0.35, p < 0.05, vert: R = − 0.43, p < 0.05) and toughness (fem: R = − 0.34, p < 0.05, vert: R = − 0.55, p < 0.01), and NEG correlated negatively with toughness at the femur (R = − 0.34, p < 0.05) and maximum strain at the vertebra (R = − 0.49, p < 0.05).Diabetes increased cortical porosity and reduced bone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility.This article is part of a Special Issue entitled “Bone and diabetes”.     

胰岛素及降糖药物治疗对2型糖尿病骨密度的影响

目的 探讨胰岛素及降糖药治疗对2型糖尿病患者骨密度的影响。均测量身高、体重,同时分析病程、糖化血红蛋白、空腹胰岛素、血清C-肽、与2型糖尿病骨质疏松的关系,讨论其影响因素和可能的机制。方法 收集276例2型糖尿病患者,根据其治疗情况分为胰岛素（A）组及降糖药物(B)组,测定上述两组患者骨密度（BMD）、体重指数（BMI）、血清C-肽、空腹血糖、糖化血红蛋白、并按病程结合年龄分组对比。结果 （1）高龄段两组骨质疏松的发病率无统计学差异;（2）早期及长期使用胰岛素治疗组骨密度较降糖药治疗组高（P<0.01）,两组相差显著。（3）骨密度与糖化血红蛋白呈负相关、与空腹胰岛素及血清C-肽呈正相关。结论 胰岛素早期干预能延缓并减低患者的骨质疏松发病率及程度,对于高龄及病程大于15年糖尿病患者,胰岛素与降糖药对其骨质疏松的防治作用无明显差异。糖化血红蛋白、空腹胰岛素、血清C-肽对骨质代谢有一定影响。     

Effects of non-enzymatic glycation on cancellous bone fragility

Post-translational modifications of collagen, such as non-enzymatic glycation (NEG), occur through the presence of extracellular sugars and cause the formation of advanced glycation end-products (AGEs). While AGEs have been shown to accumulate in a variety of collagenous human tissues and alter the tissues' functional behavior, the role of AGEs in modifying the mechanical properties of cancellous bone is not well understood. In this study, an in vitro ribosylation model was used to examine the effect of NEG on the mechanical behavior of cancellous bone. Cancellous bone cores and individual trabeculae were harvested from the femoral heads of eight fresh human cadavers and paired for ribosylation and control treatments. The cores were subjected to either unconfined compression tests or were demineralized and subjected to stress relaxation tests. The trabeculae were loaded to fracture in four-point bending. In vitro NEG significantly reduced the energy dissipation characteristics of the organic matrix as well as the post-yield properties including the stiffness loss of the individual trabeculae (p<0.05) and the damage fraction of cancellous bone (p<0.001). AGEs in cancellous bone cores from both treatment groups correlated with damage fraction (r(2)=0.36, p<0.05) and post-yield strain energy (r(2)=0.21, p<0.05); and with energy dissipation characteristics of the organic matrix (r(2)=0.35, p<0.05). In the control group, AGEs content increased up to six-fold with age (r(2)=0.95, p<0.008). This study shows that cancellous bone is susceptible to NEG that increases its propensity to fracture. Moreover, despite tissue turnover, cancellous bone may be susceptible to an age-related accumulation of AGEs.     

Insufficient renal 1-alpha hydroxylase and bone homeostasis in aged rats with insulin resistance or type 2 diabetes mellitus

This study aimed to explore the relationship between insufficient renal 1-alpha hydroxylase (IRH) and bone homeostasis in type 2 diabetes mellitus (T2DM) or insulin resistance (IR) and to investigate whether IR plays a major role in the pathogenesis of both IRH and bone loss in T2DM. The experimental animal models of T2DM, IR, IR treated with vitamin D (VD), IR treated with 1-alpha hydroxyvitamin D (1α(OH) D, the product of renal 1-alpha hydroxylase), T2DM treated with VD, and T2DM treated with 1α(OH) D were established on 18-month-old male Wistar rats. For rats in each animal model and normal control rats, IR was detected by euglycemic insulin clamp technique (EICT) and glucose infusion rate (GIR, an index of IR) was calculated. Levels of serum 25-hydroxyvitamin D (25(OH)D) and serum active vitamin D (1,25(OH)₂D) were determined by radioimmunoassay (RIA), and 1,25(OH)₂D/25(OH)D ratio (1,25-25-R, an index of renal 1-alpha hydroxylase activity in vivo) was calculated; and bone mineral density (BMD) in femoral bone and lumbar vertebrae was measured by dual-energy X-ray absorption (DEXA). No significant difference was observed among the levels of 25(OH)D in all the rats. In IR rats, 1,25(OH)₂D level, 1,25-25-R, and BMD level were significantly higher than those in T2DM rats and were lower than those in normal control rats. In the aged rats with T2DM or IR, administration of VD had no effect on 25(OH)D level, 1,25(OH)₂D level, 1,25-25-R, and BMD level. Administration of 1α(OH) D had also no effect on 25(OH)D level but increased 1,25(OH)₂D level, 1,25-25-R, and BMD level. For the aged rats with T2DM or IR, GIR positively correlated with both levels of 1,25(OH)₂D and BMD, and 1,25-25-R positively and significantly correlated with levels of BMD. In T2DM or IR, IRH is a precipitating factor for bone loss. IR seems to play a major role in the pathogenesis of both IRH and bone loss in T2DM.     

Sclerostin antibody treatment improves bone mass,bone strength,and bone defect regeneration in rats with type 2 diabetes mellitus

Type 2 diabetes mellitus results in increased risk of fracture and delayed fracture healing. ZDF fa/fa rats are an established model of type 2 diabetes mellitus with low bone mass and delayed bone healing. We tested whether a sclerostin‐neutralizing antibody (Scl‐AbVI) would reverse the skeletal deficits of diabetic ZDF rats. Femoral defects of 3 mm were created in 11‐week‐old diabetic ZDF fa/fa and nondiabetic ZDF +/+ rats and stabilized by an internal plate. Saline or 25 mg/kg Scl‐AbVI was administered subcutaneously (s.c.) twice weekly for 12 weeks (n = 9–10/group). Bone mass and strength were assessed using pQCT, micro–computed tomography (µCT), and biomechanical testing. Bone histomorphometry was used to assess bone formation, and the filling of the bone defect was analyzed by µCT. Diabetic rats displayed lower spinal and femoral bone mass compared to nondiabetic rats, and Scl‐AbVI treatment significantly enhanced bone mass of the femur and the spine of diabetic rats (p < 0.0001). Scl‐AbVI also reversed the deficit in bone strength in the diabetic rats, with 65% and 89% increases in maximum load at the femoral shaft and neck, respectively (p < 0.0001). The lower bone mass in diabetic rats was associated with a 65% decrease in vertebral bone formation rate, which Scl‐AbVI increased by sixfold, consistent with a pronounced anabolic effect. Nondiabetic rats filled 57% of the femoral defect, whereas diabetic rats filled only 21% (p < 0.05). Scl‐AbVI treatment increased defect regeneration by 47% and 74%, respectively (p < 0.05). Sclerostin antibody treatment reverses the adverse effects of type 2 diabetes mellitus on bone mass and strength, and improves bone defect regeneration in rats. © 2013 American Society for Bone and Mineral Research.     

利拉鲁肽对2型糖尿病骨质疏松大鼠miRNA-19a、miRNA-144及骨密度的影响

目的分析利拉鲁肽对2型糖尿病骨质疏松(DOP)大鼠miRNA-19a、miRNA-144及骨密度的影响。方法采用随机数表法将50只大鼠随机分为正常组、去势对照组、模型组及给药组,模型组及给药组构建2型DOP大鼠模型;去势对照组摘除双侧卵巢,后正常组、去势对照组及模型组使用生理盐水干预,给药组使用利拉鲁肽治疗;治疗结束后采集大鼠血液样本,检测血糖、胰岛素、Cad-11、IRS1、miRNA-19a及miRNA-144水平;使用双能X线骨密度检测仪检测腰椎、全身、骨盆及股骨骨密度。结果给药组血糖、miRNA-19a、miRNA-144、Cad-11及IRS1水平均明显优于模型组及去势对照组;给药组大鼠各部位骨密度明显高于去势对照组和模型组。结论利拉鲁肽可抑制糖尿病大鼠骨密度的降低,其作用可能与降低2型DOP大鼠miRNA-19a、miRNA-144水平有关。     

Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus

AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.     

Roux-en-Y gastric bypass increases hepatic and peripheral insulin sensitivity in rats with type 2 diabetes mellitus

BackgroundRoux-en-Y gastric bypass (RYGB) surgery for the treatment of obesity leads to long-term diabetes remission in approximately 80% of cases. The aim of this study was to investigate the effects of RYGB on hepatic and peripheral insulin sensitivity in type 2 diabetic rats and their possible mechanisms. We also tested the hypothesis that RYGB reduces lipid content and improves insulin sensitivity in hepatocytes and skeletal muscle cells.MethodsSprague–Dawley rats were divided into 4 groups: diabetic RYGB group (n = 18), diabetic RYGB sham group (n = 6), diabetic group (n = 6), and nondiabetic control group (n = 6). The hyperinsulinemic-euglycemic clamp with tracer infusion was completed at 2, 4, and 8 weeks postoperatively to assess insulin sensitivity. The lipid content in liver and muscle tissue was examined.ResultsPostoperatively, the diabetic RYGB group had significant decreases in weight, fat mass, and food intake. Two weeks after surgery, RYGB had significantly improved the hepatic insulin sensitivity index and decreased the hepatic triglyceride, total cholesterol, and fatty acyl-CoA content. The significantly increased insulin sensitivity and decreased lipid content in muscle were not detected until 4 weeks after RYGB surgery. The basal insulin and C-peptide concentrations were significantly lower than those in diabetic group by 2 weeks after RYGB.ConclusionThe increased insulin sensitivity after RYGB occurs earlier in the liver than in the muscle and both may contribute to long-term remission of type 2 diabetes. Reduced lipid content of hepatocytes and skeletal muscle cells after RYGB may contribute to the improved insulin sensitivity in these cells.     

Free fatty acids,glucose, and insulin in type 2 diabetes mellitus

Xu et al used the HOMA2 model to estimate the β-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels. This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities, which led to type 2 diabetes. However, significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids (FFAs) into the blood circulation, which leads to a marked reduction in membrane flexibility. These data favor a FFA-glucose-insulin axis. The authors are invited to extend their study with the introduction of the saturation index (number of carbon-carbon double bonds per 100 fatty-acyl chains), as observed in erythrocytes.     

Complement activation in obesity,insulin resistance,and type 2 diabetes mellitus

Amplified inflammatory reaction has been observed to be involved in cardiometabolic diseases such as obesity, insulin resistance, diabetes,dyslipidemia, and atherosclerosis. The complement system was originally viewed as a supportive first line of defense against microbial invaders, and research over the past decade has come to appreciate that the functions of the complement system extend beyond the defense and elimination of microbes, involving in such diverse processes as clearance of the immune complexes, complementing T and B cell immune functions, tissue regeneration, and metabolism. The focus of this review is to summarize the role of the activation of complement system and the initiation and progression of metabolic disorders including obesity, insulin resistance and diabetes mellitus. In addition, we briefly describe the interaction of the activation of the complement system with diabetic complications such as diabetic retinopathy, nephropathy and neuropathy, highlighting that targeting complement system therapeutics could be one of possible routes to slow down those aforementioned diabetic complications.     

Oxidative stress,insulin resistance,dyslipidemia and type 2 diabetes mellitus

Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus(T2DM) and this appears to underlie the development of cardiovascular disease,T2 DM and diabetic complications.Increased oxidative stress appears to be a deleterious factor leading toinsulin resistance,dyslipidemia,β-cell dysfunction,impaired glucose tolerance and ultimately leading to T2 DM.Chronic oxidative stress,hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant,have high oxidative energy requirements,decrease the gene expression of key β-cell genes and induce cell death.If β-cell functioning is impaired,it results in an under production of insulin,impairs glucose stimulated insulin secretion,fasting hyperglycemia and eventually the development of T2 DM.     

端粒及内脏脂肪对2型糖尿病患者骨密度的影响

目的 探讨端粒长度与内脏脂肪面积（visceral adipose area,VFA）在2型糖尿病（type 2 diabetes mellitus,T2DM）合并骨质疏松症（osteoporosis,OP）发病中的影响作用。方法 收集2020年6月至2021年8月我院内分泌科（为国家标准化代谢性疾病管理中心）T2DM患者160例,将T2DM患者根据骨密度（bone mineral density,BMD）中T值分为OP组、骨量减少组、骨量正常组。利用qPCR法测定外周血白细胞端粒长度。记录所有参与者的一般临床资料,检测血糖、血脂、25羟基维生素D[25(OH)D]、性激素等指标,应用双能X线测定BMD（包括股骨颈、全髋关节、腰椎）,应用生物电阻抗法测定VFA,应用SPSS 24.0统计学软件进行数据分析。结果 ①OP组、骨量减少组、骨量正常组中外周血端粒长度依次增加,OP组VFA大于骨量减少组和骨量正常组。②各部位BMD与VFA负相关,与端粒长度正相关。③端粒长度是各部位BMD的独立影响因素,VFA是股骨颈、全髋关节BMD的独立影响因素。结论 T2DM患者低BMD与较大的VFA、较短的端粒长度有关。     

Roux—en—Y胃旁路术对2型糖尿病大鼠肾功能的影响

目的探讨Roux—en—Y胃旁路术对2型糖尿病大鼠肾功能的影响。方法采用高脂高糖饮食联合腹腔注射小剂量链脲佐菌素（streptozocin,STZ,35肛∥g）方法建立2型糖尿病大鼠模型。将造模成功的糖尿病SD大鼠分为3组：糖尿病组（8只）,假手术组（8只）,手术组（14只）;另取正常SD大鼠作为正常组（8只）。术前、术后8周检测大鼠空腹血糖,术前及术后4、8周测定血清BUN、Cr;术后8周取肾组织进行病理组织学观察,计算肾脏质量指数;免疫组织化学染色方法检测肾组织纤连蛋白、Ⅳ型胶原和TGF—B1的表达,采用Real—timePCR和Westernblot检测MMP-2、MMP-9mRNA和蛋白的表达。多组比较采用单因素方差分析,两两比较采用LSD检验。结果术后8周,糖尿病组大鼠血糖、BUN、Cr、肾脏质量指数分别为（15．9±1．6）mmol／L、（9．24-0．6）mmol／L、（44±4）~mol／L、（10．7±1．5）mg／g,手术组大鼠分别为（5．9±0．7）mmol／L、（6．64-0．4）mmol／L、（304-2）~mol／L、（8．6±0．6）mg／g,两组比较,差异有统计学意义（P〈0．05）。与正常组比较,糖尿病组、假手术组大鼠肾小球体积增大,系膜增生;手术组有明显改善。正常组大鼠肾脏皮质纤连蛋白、Ⅳ型胶原、TGF—B1免疫组织化学染色积分光密度值、MMP-2、MMP-9mRNA和蛋白的表达水平分别为664±23、864-5、524-6、1．00-4-0．04、644-4、1．004-0．20、48±5,糖尿病组大鼠分别为16654-44、7894-66、4594-35、0．52±0．13、514-6、0．364-0．05、384-4,假手术组大鼠分别为1701±55、7544-49、4254-42、0．544-0．19、484-5、0．434-0．09、394-4,手术组大鼠分别为11054-61、1954-11、1474-16、1．53±0．29、634-5、1．114-0．14、49-4-5,4组比较,差异均有统计学意义（F=1340．30,4982．50,2025．10,654．19,13．58,610．74,7．86,P〈0．05）。两两比较,差异均有统计学意义（P〈0．05）。结论Roux—eFl—Y胃旁路术可改善糖尿病大鼠肾功能,减少细胞外基质沉积,其作用机制可能与抑制TGF-β1表达和上调MMP-2、MMP-9mRNA和蛋白水平有关。     

胃转流术对2型糖尿病大鼠胰岛细胞胰岛素受体及胰岛素受体底物2表达的影响

目的：探讨胃转流术对2型糖尿病大鼠胰岛细胞中胰岛素受体（IRc）及胰岛素受体底物2（IRS-2）表达的影响。 方法：高糖高脂饮食联合腹腔注射小剂量链脲佐菌素建立2型糖尿病大鼠模型,将造模成功的大鼠分为模型组和胃转流组,另取正常大鼠作为正常对照组,胃转流组大鼠行胃空肠吻合术加空肠侧侧吻合,模型组与正常对照组大鼠均行假手术。检测术前及术后8周大鼠空腹血糖、血清胰岛素,计算胰岛素敏感指数（ISI）,用免疫组化法检测胰腺组织IRc及IRS-2的表达。 结果：与正常对照组比较,模型组与胃转流组术前空腹血糖均明显升高,ISI均明显降低,但术后胃转流组两项指标均较模型组明显改善（均P<0.05）;各组胰岛素水平手术前后均无统计学差异（均P>0.05）。术后8周,胃转流组胰岛细胞IRc和IRS-2表达量均明显高于模型组（均P<0.05）,其中IRc表达量仍低于正常对照组（P<0.05）,但IRS-2表达量与正常对照组接近（P>0.05）。 结论：2型糖尿病大鼠胰岛细胞中IRc及IRS-2表达下调,而胃转流术能够使其表达显著增加,这可能是该手术产生对2型糖尿病产生疗效的机制之一。     

胃旁路术对2型糖尿病大鼠脂肪组织胰岛素受体β及胰岛素受体底物-1表达的影响

目的：观察胃旁路术对2型糖尿病大鼠（GK大鼠）脂肪组织胰岛素受体β（IR-β）及胰岛素受体底物-1（IRS-1）表达的影响,探讨其改善胰岛素抵抗的机制。方法30只8周龄雄性GK大鼠（糖尿病模型）采用数字表法分为手术组（行胃旁路手术）、假手术组（与手术组大鼠相同部位切断后原位端端吻合）和饮食配对组（与手术组大鼠同种和同等质量的饮食）,每组10只,另10只8周龄雄性SD大鼠作为空白对照组（自由进食及饮水）。检测术前与术后4周各组大鼠空腹血糖（FPG）和空腹胰岛素（FINS）水平,计算术前及术后4周胰岛素抵抗指数（HOMA-IR）,应用蛋白印迹（Western blot）技术检测各组术后4周脂肪组织IR-β和IRS-1的表达。结果手术组术后4周FPG及 HOMA-IR 较术前明显降低（分别为5.13±0.22比11.73±0.37,2.16±0.18比5.10±0.29;均P<0.05）,并能达到空白对照组术后水平（P>0.05）;而假手术组和饮食配对组较术前无显著变化（均P＞0.05）;术后4周手术组IR-β及IRS-1表达量均明显高于其他3组（均P<0.05）。结论胃旁路术能上调2型糖尿病大鼠胰岛素信号转导通路中IR-β及IRS-1的表达,改善脂肪组织胰岛素抵抗,提高胰岛素的敏感性。     

褪黑素对2型糖尿病患者骨质量的影响

目的：观察褪黑素对糖尿病患者骨质量和骨代谢生化指标的影响。方法：睡眠欠佳且骨量减少或骨质疏松的2型糖尿病患者72例,随机分成两组,分别给予褪黑素或安定改善睡眠治疗,持续治疗半年,治疗后观察跟骨超声声速,振幅衰减,血碱性磷酸酶,尿钙／肌酐比值等指标。结果：治疗装卸后,观察组声速和跟骨振幅衰减,碱性磷酸酶等指标明显高于对照组,结论：褪黑素能够明显改善糖尿病患者骨质量,减少骨质疏松发生的危险。     

硫化氢对2型糖尿病大鼠胰岛素抵抗和脂代谢的影响

目的 观察硫化氢对2型糖尿病(T2DM)大鼠胰岛素抵抗和脂代谢的影响.方法 65只大鼠采用高糖高脂饮食+腹腔注射链脲佐菌素(STZ)的方法建立T2DM模型,将45只成模大鼠随机分为糖尿病(DM)、DM+硫氢化钠(NaHS)和DM+ DL-炔丙基甘氨酸(PAG)组,每组各15只,另设正常对照组.DM+ NaHS组大鼠腹腔注射NaHS[56 μmol/(kg·d)],DM+ PAG组腹腔注射PAG[50 mg/(kg·d)],对照组和DM组给予相同体积的生理盐水,连续给药2周.给药结束后,测定大鼠空腹血糖(FBG)、胰岛素(FIns)、甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA),计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI);测定胰腺组织中硫化氢(H2S)浓度,免疫组织化学方法检测胰腺组织胰岛素表达.结果 与对照组比较,DM组大鼠FBG[(18.22±3.99) mmol/L]、TG[(1.54 ±0.16) mmol/L]、TC[(3.27±0.38) mmol/L]、FFA[(504.68±37.70) μmol/L]水平及HOMA-IR升高(P＜0.05),FIns[(41.79±3.43) mU/L]和ISI(-6.57 ±0.37)降低,胰腺组织H2S浓度[(96.98±19.44) μmol/L]升高,胰腺组织胰岛素阳性表达细胞面积(AIEP)和胰岛素阳性染色率(PRSI)降低,差异均有统计学意义(P＜0.05);与糖尿病组比较,NaHS干预后,糖尿病大鼠FBG[(25.42 ±0.21) mmol/L]、TG[(2.40 ±0.21) mmol/L]、TC[(4.80 ±0.16) mmol/L]、FFA[(633.96±25.64)μmol/L]水平及HOMA-IR升高更明显,FIns[(29.36±2.65) mU/L]和ISI(-6.58±0.27)降低,胰腺组织H2S浓度[(134.50±12.70)μmol/L]明显升高,AIEP和PRSI降低,差异均有统计学意义(P＜0.05);应用PAG后,糖尿病大鼠血浆FBG[(10.83±1.10) mmol/L]、TG[(1.30±0.12) mmol/L]、TC[(2.79 ±0.33) mmol/L]、FFA[(383.39±69.00) μmol/L]水平明显降低,胰岛素抵抗改善,FIns[(51.58±1.49) mU/L]和ISI(-6.32±0.11)明显升高,胰腺组织H2S浓度[(71.48±10.94) μmol/L]明显降低,AIEP和PRSI增加.结论 H2S通过影响T2DM大鼠胰岛素抵抗和脂代谢参与糖尿病发生发展.     

胰岛素、阿仑膦酸钠治疗新诊断老年糖尿病骨质疏松症患者骨密度及骨转换指标的研究

目的通过观察胰岛素、阿仑膦酸钠干预,观察在糖尿病骨质疏松症治疗12个月后股骨颈(Femur Neck)骨密度(BMD)及骨特异性碱性磷酸酶(BAP)、骨钙素(BGP)、抗酒石酸酸性磷酸酶-5b(TRAP-5b)等血清骨转换指标的变化。方法选取在我院治疗的糖尿病骨质疏松症患者128例,随机分成4组,即对照组(METF)、胰岛素组(INSU)、二甲双胍+阿仑膦酸钠组(METF+ALEN)、胰岛素+阿仑膦酸钠组(INSU+ALEN),每组同时服用钙尔奇D片作为基础用药,分别于服药前及服药12月后,测定4组患者股骨颈BMD及血BAP、BGP、TRAP-5b,分析治疗前后以及治疗组与对照组间的差异。结果 INSU+ALEN组治疗12月可见患者骨密度较前增加,治疗前后有统计学意义(P0.05),METF、INSU组较前无明显改变,治疗前后无统计学意义(P0.05),METF+ALEN组治疗12月可见患者BMD较前略有增加,治疗前后无统计学意义(P0.05),INSU+ALEN组治疗后BMD的增加明显高于其它组(P均0.05)。INSU+ALEN治疗组患者治疗12月后血清BAP、BGP显著升高(P0.05),TRAP-5b显著降低(P0.05);将上述指标与对照组、其它治疗组比较,BAP、BGP、TRAP-5b差异显著(P均0.01);METF、INSU、METF+ALEN组治疗12月可见患者血清BAP、BGP较前略有增加,TRAP-5b略有降低,治疗前后无统计学意义(P0.05)。结论胰岛素是糖尿病骨质疏松症首选治疗,可增加骨量,预防骨丢失。阿仑膦酸钠能抑制骨吸收,促进骨形成,减缓骨量丢失,提高骨密度,二者联用可有效防治糖尿病骨质疏松症。