替米沙坦通过抑制胰岛内质网应激减少STZ致长期高脂喂养大鼠糖尿病的发生

目的:研究肾素血管紧张素Ⅱ受体阻断剂替米沙坦对长期高脂喂养大鼠链脲佐菌素(STZ)致糖尿病的发病率和胰岛β细胞功能的影响及其作用机制。方法:以高脂高热量饮食饲养Wistar大鼠,16周后以替米沙坦干预,24周后1次性给予小剂量STZ,注射STZ1周后行静脉胰岛素释放实验检测胰岛β细胞功能;采用反转录-聚合酶链反应及免疫组化法检测胰岛内质网应激因子及胰岛素的表达。结果:与高脂+STZ组相比,高脂+替米沙坦+STZ组大鼠糖尿病发病率明显下降,胰岛素最大分泌量增加了56.9%,早期胰岛素分泌指数(EISI)及急性胰岛素分泌反应(AIR)升高了1.98倍和0.88倍,β细胞内胰岛素表达量及胰岛素阳性表达细胞密度明显增加,胰岛β细胞内质网应激凋亡相关分子免疫球蛋白结合蛋白、C/EBP同源蛋白基因表达及Bax蛋白表达均显著下降。结论:肾素血管紧张素系统(RAS)阻断可以增强长期高脂喂养大鼠对STZ性糖尿病的抵抗性,减少β细胞内质网应激介导的凋亡因子的表达。减弱胰岛内质网应激可能是RAS阻断而改善β细胞功能、减少糖尿病发生的重要机制之一。     

限食对高脂喂养大鼠肝脏内质网应激的影响

目的：观察限食对高脂喂养大鼠肝脏内质网应激标志伴侣蛋白78 kD糖调节蛋白（GRP78）mRNA表达的影响，以进一步了解饮食控制对肥胖及胰岛素抵抗影响的机制。方法：雄性Wistar大鼠24只，随机分为正常对照组（NC）、高脂饮食组（HF）、热卡限制组（CR），每组8只。NC组和HF组分别给予普通饲料（脂肪热卡比18.94%）和高脂饲料（脂肪热卡比50.55%）喂养12周，自由进食。CR组给予自由高脂饲料8周后，改为半量正常饲料（半量为同龄对照组自由进食量的一半）继续喂养4周。造模结束后检测动物胰岛素抵抗指数（HOMAIR）、内脏脂肪重量/体重比值和血清生化指标变化，光镜和电镜下观察大鼠肝脏组织学改变，RT-PCR半定量检测大鼠肝脏GRP78 mRNA的表达。结果：（1）HF组空腹血胰岛素(FIns) (27.51±3.51) mU/L vs (15.46±2.25) mU/L、甘油三酯（TG）(1.35±0.25) mmol/L vs (0.67±0.10) mmol/L、胆固醇（TC）(2.59±0.34) mmol/L vs (1.41±0.28) mmol/L及胰岛素抵抗指数HOMAIR(5.85±0.23) vs (2.85±0.60)较NC组明显升高(P＜0.01)，且肝脏中脂质沉积明显。（2）限食4周后，CR组的Fins(11.25±2.42) mU/L vs (27.51±3.51) mU/L、TG(0.45±0.06) mmol/L vs (1.35±0.25) mmol/L、TC(1.06±0.15) mmol/L vs (2.59±0.34) mmol/L和HOMAIR(1.91±0.38) vs (5.85±0.23)明显低于HF组(P＜0.01)，同时肝脏中脂质沉积也减轻。（3）电镜下，HF组内质网肿胀断裂，核糖体脱落，糖原溶解，CR组则基本恢复正常。（4）HF组大鼠肝脏中GRP78 mRNA表达明显高于NC组（29.36±3.54 vs 16.51±1.73），而CR组则明显低于HF组（13.70±2.35 vs 29.36±3.54）。结论：合理限制饮食能有效减轻高脂喂养所致的脂质代谢紊乱和胰岛素抵抗，其作用机制至少与肝脏组织中的内质网应激相关蛋白GRP78的mRNA表达受抑有关。     

葡萄糖毒性与胰岛β细胞功能

人们已了解到长期高血糖不仅是代谢控制不良的一个标志,而且它与胰岛素分泌和胰岛素抵抗有着密切的关系。高血糖具有双向性作用,短期的高血糖对胰岛素的分泌和葡萄糖的利用有着刺激作用,长期的高血糖则起相反的抑制作用。这种长期高血糖的有害作用被称之为“葡萄糖毒性”[1]。1     

肾上腺髓质素加强高糖对自发性高血压大鼠胰岛β细胞的毒性作用

探讨高糖是否对自发性高血压大鼠 (SHR)和 Wistar- Kyoto(WKY)鼠胰岛 β细胞分泌功能具有抑制作用 ,肾上腺髓质素 (adrenomedullin,AM)能否加强此抑制作用。选取 6周龄 SHR鼠及 10周龄 WKY鼠各 10只 ,分离胰岛放入 12孔培养板内 (90个胰岛 /孔 )培养。先以含 5 .6 m mol/ L(m M)葡萄糖的 RPMI16 4 0培养基培养 1h,取出培养液。然后用含 2 0 m M葡萄糖及不同浓度 AM(分别是 0 ,10 - 8,10 - 7,10 - 6 M)的 RPMI 16 4 0培养基培养 1小时 ,取出培养液 ,放射免疫分析 (RIA)方法测定两次培养液的胰岛素含量。 SHR鼠的胰岛细胞经用不加 AM含 2 0m M葡萄糖的 16 4 0培养基培养 1h后 ,与用含 5 .6 m M葡萄糖的 16 4 0培养基培养 1h相比 ,其培养液中胰岛素含量明显降低 (分别是 19.9± 6 .6 vs6 0 .9± 33.6 m U/ L,P<0 .0 5 )。当用含 2 0 m M葡萄糖及不同浓度 AM的 16 4 0培养基培养时 ,随着 AM浓度的增加 ,培养液中的胰岛素含量进一步减少 (19.9± 6 .6 vs2 2 .2± 8.0 vs2 1.5± 5 .6 vs17.9± 3.6 m U/ L)。对照组 WKY鼠的胰岛细胞经上述相同方法处理后得出相似的结果。但 WKY鼠与 SHR鼠相比 ,其胰岛细胞经用含 5 .6 m M及 2 0 m M葡萄糖培养基培养后培养液中的胰岛素含量较高 (P<0 .0 1)。用高糖培养基培养     

促胰素对大鼠胰岛细胞增殖及功能的影响

背景：有研究报道,促进胰岛β细胞增殖分化和再生是2型糖尿病患者一种潜在的治疗方案。 目的：观察促胰素对体外培养大鼠胰岛细胞增殖及功能的影响。 方法：采用胶原酶消化和组织培养法分离纯化大鼠胰岛细胞,检测其纯度和活性,将胰岛细胞分为空白对照组和实验组,空白对照组加入普通培养基,实验组培养基中加入不同质量浓度(100,200,300,400 mg/L)促胰素,培养1,3,5 d后CCK-8法检测细胞增殖活性;培养5 d后行低糖和高糖刺激胰岛素释放实验。 结果与结论：随着促胰素质量浓度的增高,胰岛细胞增殖活性呈剂量依赖性增加(P < 0.05),但无明显时间依赖性。除100,200 mg/L组外,300,400 mg/L两组胰岛素分泌量均显著高于空白对照组(P < 0.05)。表明300,400 mg/L促胰素不仅可促进胰岛细胞增殖,而且可显著增强胰岛细胞分泌胰岛素的功能。 关键词：促胰素;胰岛细胞;增殖;胰岛功能;胰岛分离;纯化 doi:10.3969/j.issn.1673-8225.2012.05.027     

高脂饮食喂养对大鼠骨骼肌细胞膜GLUT4含量的影响

目的:检测骨骼肌细胞膜GLUT4含量的改变,探讨高脂饮食喂养诱导胰岛素抵抗的受体后机制。方法:将动物分为3组:①正常对照组;②高脂饮食组;③高脂饮食+饮食控制组。通过8周高脂饮食喂养建立胰岛素抵抗大鼠模型,随后代以普通饮食继续喂养4周。用Westernblot方法检测骨骼肌细胞膜表面GLUT4蛋白表达。结果:在胰岛素刺激下,高脂饮食组大鼠骨骼肌细胞膜GLUT4蛋白表达显著少于正常对照组(减少约31%);饮食控制组骨骼肌细胞膜GLUT4蛋白表达明显高于高脂饮食组(约1.14倍)。结论:高脂喂养的方法可成功复制出胰岛素抵抗大鼠模型;高脂饮食可能通过影响胰岛素信号转导系统,使胰岛素刺激的GLUT4转位至细胞膜受阻,其在膜上的含量也降低,从而促进胰岛素抵抗的形成和发展。     

SD大鼠胰岛的分离纯化及培养

目的探讨分离纯化大鼠胰岛素分泌细胞的方法,并评价细胞的生物学特性。方法选用3～4周龄健康成年SD大鼠,常规外科手术显露SD大鼠胰腺和胆总管,在胆总管内插入4.5～5号头皮针后固定,逆行注入预冷的0.5mg/ml的胶原酶V溶液8～10ml,使胰腺膨胀后迅速取出胰腺放入6mlHanks液中38℃消化10min,用含10%胎牛血清的Hanks液终止消化,60目筛网过滤后用Ficoll400非连续梯度离心纯化胰岛。纯化后的细胞用DTZ染色和胰岛素释放试验来分析胰岛素的分泌情况。结果 DTZ染色后β细胞胞浆着色,为均一的猩红色。胰岛细胞分布于Ficoll400浓度为23%～20%和20%～11%的界面之间,纯度高达90%,并且细胞的胰岛素分泌情况良好。结论胶原酶V消化,Ficoll400纯化是一种简单高效的胰岛素分泌细胞分离纯化的方法,可以获取数量多,活性和纯度好的胰岛素分泌细胞。     

糖调节受损合并高胰岛素血症患者的胰岛功能评估及其影响因素分析

目的 评价糖调节受损合并高胰岛素血症患者的胰岛功能,分析其影响因素.方法 选取北京地区中老年男性共计547例,行75g口服葡萄糖耐量(OGTF)试验,根据美国糖尿病协会(ADA) 2003年标准分为三组:空腹血糖受损(IFG)325例、糖耐量减低(IGT)126例和空腹血糖受损合并糖耐量减低(IFG/IGT) 96例;各组根据胰岛素测定结果再分为高胰岛素血症组(HINS)以及非高胰岛素血症组(非HINS),对比各组间的代谢特征、胰岛素抵抗和胰岛β细胞分泌功能,评估合并代谢综合征相关疾病的差异.结果 ①高胰岛素血症患者IFG组和IFG/IGT组的胰岛素抵抗指数(HOMA-IR)分别是IGT组的1.42倍和1.41倍(P＜0.05);非HINS人群胰岛素抵抗情况与之类似:②高胰岛素血症患者胰岛分泌功能IFG/IGT组受损最为严重,其HOMAβ细胞功能指数(HBCI)分别是IGT和IFG组的74.04％和80.98％ (P ＜0.05);经HOMA-IR校正后,与IGT组的显著性差异更加明显,而与IFG组的差异消失;③三组糖调节受损-高胰岛素血症组合并代谢异常疾病的构成比均较相应非HINS组明显升高;IFG/ IGT组合并肥胖、高血压和高脂血症的构成比最高.结论 ①高胰岛素合并IFG主要的病理机制为肝脏的胰岛素抵抗;②高胰岛素血症合并IGT基础状态的胰岛分泌功能优于合并IFG者;③高胰岛素血症更易合并多种代谢紊乱,尤其是IFG/IGT患者,需要综合干预.     

microRNA-375通过下调Neurod1介导高糖引起胰岛β细胞功能损伤

目的 研究miR-375是否能够参与高糖引起的胰岛β细胞功能损伤,并对其具体机制进行初步探索.方法 用高糖刺激大鼠胰岛β细胞系INS-1细胞,钾刺激的胰岛素分泌(KSIS)实验检测INS-1细胞胰岛素分泌功能,运用酸乙醇抽提检测胰岛素含量,定量RT-PCR检测miR-375的表达情况.Western印记检测Neurod1的蛋白水平.结果 高糖刺激能够损伤INS-1细胞KSIS功能,降低胰岛素含量;高糖刺激同时可以升高miR-375表达水平,而过表达miR-375确实能够损伤INS-1细胞功能;miR-375能够抑制Neurod1的表达水平,干扰miR-375可以通过恢复Neurod1的表达,进而逆转高糖刺激引起的INS-1细胞KSIS功能损伤.结论 miR-375通过降低Neurod1蛋白水平介导高糖引起的胰岛β细胞功能损伤.     

血糖峰值时间与胰岛β细胞功能

目的：探讨糖负荷后血糖峰值时间与胰岛β细胞功能和胰岛素抵抗的关系。方法分析2012年~2014年首次于我院内分泌科门诊行口服葡萄糖耐量(OGTT)、胰岛素释放试验(OGIRT)、糖化血红蛋白(HbA1c)检查者的血糖、胰岛素、糖化血红蛋白值,根据糖负荷后血糖峰值时间分3组院30min组(T30)、60min组(T60)和120min组(T120),分析各组间血糖、血糖波动(AGF)、HbA1c、胰岛素、HOMA-IR、rI30/rG30、HOMA-β及AUC-i的差别。结果糖耐量正常(NGT)、糖调节受损(IGT/IFG)和糖尿病(DM)组患者T30比例逐渐减少,T60和T120比例逐渐增多;随着血糖峰值时间后延,OGTT各点血糖和HbA1c水平逐渐升高,AGF逐渐增大;rI30/rG30、HOMA-β及AUC-i逐渐降低,HOMA-IR逐渐增加。结论随着OGTT后血糖峰值时间后延,胰岛β细胞功能逐渐减退,胰岛素抵抗逐渐增加,糖负荷后血糖峰值时间可以评价胰岛β细胞功能状态。     

Metabolic strategies to predict and improve intrahepatic islet graft function

The success rate of intraportal islet grafts and the length of graft survival have been low and variable in diabetic humans. Goal of this work was to outline the principal strategies to predict and improve islet graft. The study of 15 insulin dependent diabetic patients after islet and kidney transplantation allowed us to build a metabolic database. The patients received an hyperglycemic clamp to assess insulin secretion and a euglycemic clamp in combination with tracers of glucose, amino acid and lipid metabolism andindirect calorimetry to assess insulin action. The results of this initial study were used to design new metabolic strategies to predict and improve islet graft function. Special emphasis is given to the importance of developing and studying the metabolic phenotype of transgenic animals with the knock out or the overexpression of genes involved in specific metabolic pathways.     

Early islets and mesenchyme from an injured adult pancreas improve syngeneic engraftments and islet graft function in diabetic rats

A decrease in mass of isografts and a decline in islet function are major challenges in islet transplantations. Despite this, transplantation of 84?h harvested pancreatic duct ligation (PDL) tissues have been shown to have the same functional ability to foetal pancreata, but there was only 40% success in reverting hyperglycaemia. We tested the potential of early islets with mesenchymal stromal cells (MSCs) to promote isogeneic grafts survival and to restore normoglycemia in diabetic rats, in comparison with late islets. Islets were isolated from injured adult pancreata of donor rats at 24?h post ligation either with MSCs (24?h islet/MSC+) or without MSCs (24?h islet/MSC-), and at 84?h without MSCs (84?h islet/MSC-). These cells were transplanted under the renal capsule of syngeneic STZ-diabetic recipient rats. The islet grafts were monitored using the BGLs of recipients and the immunohistomorphology of the grafts were analysed using anti-insulin and anti-Ki67 antibodies. The mean BGL in 24?h islet/MSC+ recipients was reduced over time toward the control value. The curves of the mean BGLs in the control islet/MSC- and the 24?h islet/MSC- recipients dropped significantly below the control normal glucose group’s levels to reach their nadirs on weeks 4 and 6, respectively. Both curves had a peak overshoot on week 9, with no statistical significant difference between them. Engrafted islets were evident in these recipients, lasted for 5 and 6 weeks and correspondingly survived failure. However, insulin+ cells were present in the isografts of all recipients; but, only isografts in the 24?h islet/MSC+ presented with a homogenous subcapsular beta cell mass. In addition, the tendency of 24?h islet/MSC- to restore normoglycaemia with its survival capacity was statistically highly significant compared to the 84 islet/MSC- recipients (80%; 20%; p?=?0.001). Transplantation of early islets with MSCs from injured adult pancreata prolongs islet graft survival and improves isograft function in diabetic rats. This novel observation requires much further exploration for its clinical application, but this model already provides hope for new sources of donor islets for transplantation.     

C-reactive protein concentration is not related to islet autoimmunity status in offspring of parents with type 1 diabetes

Autoimmunity may be associated with acute or chronic inflammation. In order to determine whether the inflammatory marker C-reactive protein (CRP) was an indicator of inflammatory events that precede, predict, or associate with islet autoimmunity or type 1 diabetes, CRP was measured in sequential antibody-negative, seroconversion, and follow-up-positive samples from 65 prospectively studied islet autoantibody-positive children. Although changes in CRP concentrations were observed in some children, overall CRP concentrations were similar in antibody-negative samples (median, 0.21 mg/L), antibody-positive samples (median, 0.26 mg/L), and samples at seroconversion (median, 0.26 mg/L). CRP concentrations at diabetes onset (median, 0.59 mg/L) were not significantly increased over antibody-negative samples (P = 0.07). CRP concentrations did not predict diabetes development. CRP concentrations were related to age (r = 0.26; P < 0.001) and were increased in samples obtained from October to January (P < 0.001). These findings suggest that CRP concentrations are not a valuable marker of progression to type 1 diabetes and highlight the importance of correcting analyses for seasonal variations.     

阻断肾素血管紧张素系统对长期高脂喂养胰岛素抵抗大鼠胰岛UCP2和GCLC表达的影响

目的： 观察长期高脂喂养的胰岛素抵抗大鼠胰岛氧化应激机制以及阻断肾素血管紧张素系统（RAS）对其的影响,探讨RAS与氧化应激、糖代谢之间的关系。方法: 雄性Wistar大鼠分为正常饲养组（NC组）、高脂饲养组（HF组）、高脂+培哚普利组（FP组）、高脂+替米沙坦组（FM组）,后2组大鼠喂养16周后分别以培哚普利2 mg·kg-1·d-1（FP组,n=15）和替米沙坦10 mg·kg-1·d-1（FM组,n=15）干预,8周后行正常血糖高胰岛素钳夹试验评估外周胰岛素抵抗程度,行静脉葡萄糖耐量试验检测胰岛β细胞功能 ,以RT-PCR检测γ谷氨酰半胱氨酸连接酶的催化亚基（GCLC）的表达,以免疫组化法检测胰岛局部线粒体解偶联蛋白2（UCP2）水平,以比色法测定胰腺组织丙二醛（MDA）的含量。结果: 与正常饲养组相比,高脂饲养组的葡萄糖输注率（GIR）降低了31.8%,胰岛GCLC表达降低了31.5% ,局部UCP2相对浓度增加了17.0%,胰腺MDA含量增加了0.46倍（均P<0.01）,0-10 min胰岛素曲线下面积（AUC10-10）为(271.8±33.8)vs（282.7±29.8）mIU·L-1·min-1,糖刺激后早期胰岛素分泌降低,但无显著差异;培哚普利或替米沙坦干预后,GIR分别增加了27.8%和30.8%,胰岛GCLC表达分别增加了26.6%和26.6% ,局部UCP2相对浓度分别下降了13.0%和15.6%,胰腺MDA含量分别下降了18%和20%（均P<0.01）,FP、FM组之间无显著差异。结论: 阻断RAS可以改善高脂喂养大鼠的胰岛素抵抗和胰岛β细胞分泌功能,其机制可能为通过下调胰岛局部UCP2和上调GCLC的表达,减轻氧化应激损伤,从而保护胰岛β细胞功能。     

Cystic cholangiomas after transplantation of pancreatic islets into the livers of diabetic rats

Islet transplantation is increasingly used as a therapy for human type 1 diabetes mellitus. In our study, we investigated the effect of the transplantation of a low number (n=350) of pancreatic islets into the right liver part on the neighboring portal bile ducts. Male streptozotocin- diabetic Lewis or autoimmune-diabetic BB/Pfd rats (n=1065) were subdivided into 11 experimental groups. A few days after low-number islet transplantation, cholangiocytes adjacent to the grafts showed an increase in proliferative activity. During the next 12–24 months, many peri-insular ductules progressed via tumor-like cystic lesions to large cystic cholangiomas, accompanied by a translocation of the insulin receptor into the cytoplasm and an increase in expression of insulin-related signaling proteins (Insulin-receptor-substrate-1, Raf-1, Mek-1). After 24 months, 53% of rats with low-number transplantation exhibited at least one cholangioma >10 mm, significantly outnumbering tumor development in the transplant-free left liver part and in any control group. No cholangiocarcinomas emerged. A graft cell origin of the tumors was excluded by Y chromosome in situ hybridization in cross-gender transplantations. Conclusively, low-number intrahepatic islet transplantation, most likely acting by permanent local hyperinsulinism, leads to prolonged cholangiocellular proliferation in streptozotocin- and in autoimmune-diabetic rats, resulting in the development of benign cystic cholangiomas.     

高脂饮食导致大鼠肝脏胰岛素抵抗的作用机制研究

目的: 本研究旨在建立SD大鼠胰岛素抵抗模型,观察高脂饲料喂养的SD大鼠肝脏中氧化应激以及胰岛素抵抗的发生,分析胰岛素抵抗状态下活性氧(ROS)的变化,初步探讨ROS的主要来源。方法: 以高脂饲料喂养6只4周龄雄性SD大鼠12周,建立大鼠胰岛素抵抗模型。用优越血糖仪以电子感应法测定血糖,放射免疫法检测血清胰岛素水平。二氢乙啶(DHE)染色观察肝脏组织中的ROS水平。Western blotting检测NADPH氧化酶3(NOX3)的表达。结果: 以高脂饲料喂养12周后,大鼠空腹血糖水平略有上升,但与对照组的大鼠相比无显著差异,而胰岛素敏感指数降低。蒽酮法的检测结果显示高脂饲料喂养大鼠肝组织糖原含量显著降低,高脂饮食大鼠肝组织中NOX3的表达显著增加,DHE染色显示肝组织ROS水平显著增加,提示ROS在肝胰岛素抵抗发生中起重要作用。结论: 高脂饲料喂养SD大鼠胰岛素敏感指数降低,肝组织中NOX3表达和ROS水平显著增加,糖原含量显著降低。     

Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding

A recent growing number of evidences shows that the increased prevalence of obesity and type 2 diabetes cannot be solely attributed to changes in the human genome, nutritional habits, or reduction of physical activity in our daily lives. Gut microflora may play an even more important role in maintaining human health. Recent data suggests that gut microbiota affects host nutritional metabolism with consequences on energy storage. Several mechanisms are proposed, linking events occurring in the colon and the regulation of energy metabolism. The present review discusses new findings that may explain how gut microbiota can be involved in the development of obesity and insulin resistance. Recently, studies have highlighted some key aspects of the mammalian host-gut microbial relationship. Gut microbiota could now be considered as a "microbial organ" localized within the host. Therefore, specific strategies aiming to regulate gut microbiota could be useful means to reduce the impact of high-fat feeding on the occurrence of metabolic diseases.     

YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance

Objective and design. YKL-40 participates in inflammatory states and vascular processes, which implies that comparison can be made with other inflammatory markers associated with insulin resistance and type 2 diabetes (T2D). In the present study levels of plasma YKL-40 and serum hsCRP were evaluated in patients with T2D. Materials and methods. Patients with T2D and age-matched healthy controls participated in the study. Insulin resistance was estimated using HOMA-IR model. Biochemical parameters were measured in venous blood after a 10 h fast. Results. Patients with T2D were insulin resistant (p < 0.001) and had raised levels of plasma YKL-40 (p < 0.001) and serum hsCRP (p < 0.001). YKL-40 was correlated with HOMA-IR (r = 0.23, p < 0.01), NEFA (r = 0.32, p < 0.001) and triglycerides (r = 0.24, p < 0.05). YKL-40 and hsCRP were not correlated (r = 0.17, p = NS). All participants with hsCRP < 1 mg/l had higher insulin sensitivity (p < 0.05 and p < 0.01, respectively). HsCRP were predicted by HOMA-IR and BMI (r² = 0.48, p < 0.01). Plasma YKL-40 was predicted by HOMA-IR and triglycerides (r² = 0.27, p < 0.01). Conclusions. YKL-40 and hsCRP are elevated in patients with T2D and are related to insulin resistance. No correlation was found between YKL-40 and hsCRP indicating that increased levels of YKL-40 occur independently from elevated plasma hsCRP. Received 17 September 2005; returned for revision 17 October 2005; accepted by I. Ahnfelt-R?nne 18 October 2005     

Insulin-induced hyperphagia in alloxan-diabetic rats fed a high-fat diet.

Alloxan-diabetic rats fed a standard, low-fat diet lost body weight and were hyperphagic; those fed a high-fat diet lost comparable amounts of weight, but did not overeat compared to normal animals. When given injections of protamine-zinc insulin, all diabetic rats gained weight; however, while those fed the low-fat reduced food intake from elevated levels, diabetics fed the high-fat diet became hyperphagic. Diabetic rats maintained on a high-fat diet increased food intake during long-term insulin treatment sooner and to a greater extent than normal controls. These findings are interpreted in light of the effects of insulin on storage and supply of metabolic fuels.