中国汉族人群肿瘤坏死因子-α(TNF-α)基因-238G/A和-308G/A多态性与强迫症的关联分析

目的:探讨在中国汉族人群中强迫症与TNF-a基因-238G/A和-308G/A多态性之间的关联.方法:我们的研究所招募的161例强迫症患者和325.名健康对照中,应用PCR-RFLP比较了OCD组和对照组之间的TNF-α基因在-238G/A(rs361525)和-308G/A(rs1800629)位点的基因型和等位基因频率多态性.结果:在中国大陆汉族人群TNF-α基因的OCD组与对照组之间-308 G/A等位基因频率及-238G/A的基因型频率和等位基因频率无显着差异,而-308G/A基因型频率有显著不同.在-308G/A位点,女性强迫症患者和对照组之间的基因型频率关联分析有增高的趋势.结论:我们的研究结果表明,肿瘤坏死因子-α在-308G/A点位多态性可能会影响在中国大陆汉族人群强迫症的发展.     

合作猪SLA-DQA基因第4外显子多态性分析

合作猪的MHC-DQA基因的适应性变异,其抗原识别区域(即外显子4)通过PCR扩增和随后的单链构象多态性(SSCP)和序列分析,结果显示在439个合作猪个体,SLA-DQA第4外显子检出4个等位基因和6个基因型(AA、BB、DD、AB、AC和AD),其中A等位基因和AA基因型的频率最高,为优势基因和优势基因型。对不同型的PCR-SSCP条带测序分析,发现7个突变位点(5 068 bp T→C,5 109 bp和5 149 bp处缺失C,5 131 bp A→G导致丝氨酸变为甘氨酸,5 135 bp C→T,5 234 bp G→A,5 136 bp处插入A)。遗传学分析发现,合作猪多态信息含量(PIC)为0.240 1,属于低度多态,各种基因型的分布不显著。研究结果证实,合作猪SLA—DQA基因第4外显子为低度多态。     

两个国内小型猪品种GH基因部分序列的多态性分析

目的对西藏小型猪和广西巴马小型猪生长激素基因（GH基因）部分序列的多态性进行分析。方法采用内切酶ApaI和Hin6I对西藏小型猪（108头）和广西巴马小型猪（132头）GH基因-119 bp～＋486 bp之间的区域进行PCR-RFLPs分析。结果 （1）从ApaI酶切产生的结果来看,ApaI酶切产生A（449 bp＋101 bp＋55bp）,B（316 bp＋133 bp＋101 bp＋55 bp）两种等位基因。等位基因A的频率高于等位基因B,等位基因A为优势基因。AA基因型频率高于AB和BB基因型频率;（2）从Hin6I酶切产生的结果来看,Hin6I酶切产生G1（605bp）、G2（498 bp＋107 bp）、G3（449 bp＋156 bp）、G4（449 bp＋107 bp＋49 bp）四种等位基因。等位基因G4的频率高于等位基因G1、G2、G3。等位基因G1频率很低。基因型G2G3、G2G4、G3G4、G4G4的频率较高。（3）由酶切产生的基因和基因型多态性,发现西藏小型猪与广西巴马小型猪在该基因部分序列差异不显著（P〉0.05）。结论国内的优质实验用小型猪,如西藏小型猪和广西巴马小型猪等位基因A频率均较高。     

BsaH Ⅰ对猪激素敏感脂肪酶基因外显子Ⅰ的PCR-RFLP分析

以华北野猪、东北野猪和山西黑猪、长白猪、大白猪、马身猪共计287头猪作为研究对象,对其HSL基因外显子Ⅰ区域进行了PCR-RFLP多态性研究,发现不同品种猪间存在多态性。瘦肉型大白猪、长白猪全部表现为GG基因型;山西黑猪表现为AA、AG和GG三种基因型;脂肪型地方猪种马身猪为单一的AA基因型;华北杂种野猪、东北纯种野猪及杂种野猪表现为AG和GG两种基因型。等位基因A、G及三种基因型的频率在不同猪种中不同。该研究首次对华北及东北野猪HSL基因进行了多态性研究,丰富了国内外对野猪的分子生物学研究,为野猪遗传资源的合理开发利用提供了依据。     

中国汉族人群肿瘤坏死因子-α（TNF-α）基因-238G/A和-308G/A多态性与强迫症的关联分析（英文）

目的：探讨在中国汉族人群中强迫症与TNF-a基因-238G/A和-308G/A多态性之间的关联。方法：我们的研究所招募的161例强迫症患者和325名健康对照中,应用PCR-RFLP比较了OCD组和对照组之间的TNF-α基因在-238G/A（rs361525）和-308G/A（rs1800629）位点的基因型和等位基因频率多态性。结果：在中国大陆汉族人群TNF-α基因的OCD组与对照组之间-308 G/A等位基因频率及-238G/A的基因型频率和等位基因频率无显着差异,而-308G/A基因型频率有显著不同。在-308G/A位点,女性强迫症患者和对照组之间的基因型频率关联分析有增高的趋势。结论：我们的研究结果表明,肿瘤坏死因子-α在-308G/A点位多态性可能会影响在中国大陆汉族人群强迫症的发展。     

不同品种猪HSL基因5′-UTR和外显子Ⅰ片段的克隆测序及多态性分析

激素敏感脂肪酶(Hormone sensitivelipase,HSL)是负责分解脂肪组织中甘油三酯释放游离脂肪酸的关键和限速酶,也是影响动物脂肪沉积的关键酶。将HSL基因作为影响猪脂肪代谢和沉积相关性状的候选基因,对不同品种猪HSL基因 5′ UTR和外显子Ⅰ片段进行了克隆测序并开展多态性与性状间的关系研究。序列比较发现,在测定的HSL基因靠近起始密码子(ATG)的 419bp中,杜洛克、梅山猪、大白猪和清平猪序列完全一致,与长白猪序列比较,在-13 ~-12bp位置存在GC→CG的碱基变异;梅山猪(3个体)、通城猪(3个体 )、长白猪 (3个体 )、大白猪(3个体)HSL基因外显子Ⅰ的 442bp位置有G→A碱基间的变异,G→A的转换改变了限制性内切酶BsaHⅠ酶识别位点,且导致了编码氨基酸Val→Ile的替换。经PCR RFLP分析,HSL基因外显子ⅠBsaHⅠ位点多态性有AA、AG和GG 3种基因型。“大白×梅山”F2 代资源家系猪BsaHⅠ位点不同基因型个体背膘厚、肌内脂肪等性状协方差统计分析发现,AG基因型和GG基因型在眼肌面积上存在显著差异。     

BsaH I对猪激素敏感脂肪酶基因外显子I的PCR-RFLP分析

以华北野猪、东北野猪和山西黑猪、长白猪、大白猪、马身猪共计287头猪作为研究对象,对其HSL基因外显子I区域进行了PCR-RFLP多态性研究,发现不同品种猪间存在多态性.瘦肉型大白猪、长白猪全部表现为GG基因型;山西黑猪表现为AA、AG和GG三种基因型;脂肪型地方猪种马身猪为单一的AA基因型;华北杂种野猪、东北纯种野猪及杂种野猪表现为AG和GG两种基因型.等位基因A、G及三种基因型的频率在不同猪种中不同.该研究首次对华北及东北野猪HSL基因进行了多态性研究,丰富了国内外对野猪的分子生物学研究,为野猪遗传资源的合理开发利用提供了依据.     

猪apoC3基因的遗传变异分析

目的:探究猪apoC3基因多态性,为进一步探讨其对脂肪沉积的影响和表达调控等研究提供依据。方法:选取具有不同脂肪沉积特点的3个猪种(可乐猪、贵州白香猪和大约克猪)构建品种DNA池并进行测序,结合各SNP位点测序峰高比值估算等位基因频率,并利用在线软件对不同基因型的转录结合位点及mRNA二级结构进行预测。结果:在3个猪种的apoC3基因中共发现17个SNPs(2个位于5’侧翼区;1个位于外显子3中,为同义突变;1个位于3’非翻译区,其它13个分别位于3个不同内含子中),其中C813G变异增加了一个转录因子GATA-2结合位点,G2280A变异导致mRNA二级结构最小自由能增加0.4kkal/mol。结论:不同猪种间apoC3基因SNPs位点等位基因频率差异较大,而apoC3基因编码区相对保守。     

贵州宗地花猪的GDF9基因多态性及生物信息学分析

以贵州宗地花猪和贵州从江香猪2个地方猪种为研究对象,构建基因组DNA池,扩增GDF9基因第1外显子和第2外显子序列,采用直接测序法对2个品种的GDF9基因进行单核苷酸多态性进行检测,利用生物信息学软件预测不同多态性位点对GDF9基因m RNA二级结构、蛋白质二级结构的影响。结果表明,在2个品种中共检测到T~(997)A、C~(1009)T、T~(1014)C、G~(1137)T和A~(1196)T 5个SNPs位点,其全位于第二外显子上。T~(997)A、C~(1009)T和A~(1196)T均为错义突变。T~(997)A导致编码的苯丙氨酸(Phe)变为异亮氨酸(Ile)、C~(1009)T导致编码的亮氨酸(Leu)变为苯丙氨酸(Phe)、A~(1196)T导致编码的赖氨酸(Lys)变为甲硫氨酸(Met)。SNPs位点对于GDF9基因的m RNA二级结构、蛋白质二级结构有一定影响。     

鸡、鸭甲状腺激素应答基因(THRSP)的研究进展

甲状腺激素应答Spot 14(Thyroid hormone responsive spot 14, THRSP)是一个参与多种脂肪合成限速酶基因表达的转录调控因子, 在动物肝脏、乳腺和脂肪组织中高度表达。家禽中鸡和鸭THRSP基因在cDNA水平均发现THRSPα和THRSPβ两种同工型, 其中鸡THRSPα基因编码区碱基的插入/缺失影响鸡体重和腹脂性状, 与鸡的生长发育和脂肪代谢有关。文章综述了鸡THRSP基因与鸭同源基因结构特性和表达差异, 以及鸡、鸭THRSP基因多态性及其遗传效应。     

Evolutionary adaptation to freeze-thaw-growth cycles in Escherichia coli

Fifteen populations of Escherichia coli were propagated for 150 freeze-thaw-growth (FTG) cycles in order to study the phenotypic and genetic changes that evolve under these stressful conditions. Here we present the phenotypic differences between the evolved lines and their progenitors as measured by competition experiments and growth curves. Three FTG lines evolved from an ancestral strain that was previously used to start a long-term evolution experiment, while the other 12 FTG lines are derived from clones that had previously evolved for 20,000 generations at constant 37 degrees C. Competition experiments indicate that the former FTG group improved their mean fitness under the FTG regime by about 90% relative to their progenitor, while the latter FTG group gained on average about 60% relative to their own progenitors. These increases in fitness result from both improved survival during freezing and thawing and more rapid recovery to initiate exponential growth after thawing. This shorter lag phase is specific to recovery after freezing and thawing. Future work will seek to identify the mutations responsible for evolutionary adaptation to the FTG environment and use them to explore the physiological mechanisms that allow increased survival and more rapid recovery.     

Mechanisms underlying the cardioinhibitory and pressor responses elicited from the medullary neurons in the gigantocellular tegmental field of cats

A stimulation of the gigantocellular tegmental field (FTG) in the medulla oblongata often increases systemic arterial blood pressure (SAP) and decreases heart rate (HR). We investigated if the cardioinhibitory/depressor areas, including the nucleus ambiguus (NA), the dorsal motor nucleus of vagus (DMV) and the caudal ventrolateral medulla (CVLM), underlied the functional expression of FTG neurons in regulating cardiovascular responses. In 73 chloralose-urethane anesthetized cats, the HR, SAP and vertebral nerve activity (VNA) were recorded. Neurons in the FTG, NA, DMV and CVLM were stimulated by microinjection of sodium glutamate (25 mM Glu, 70 nl). To study if the NA, DMV, and CVLM relayed the cardioinhibitory messages from the FTG, 24 mM kainic acid (KA, 100 nl) was used as an excitotoxic agent to lesion neurons in the NA, DMV or CVLM. We found that the cardioinhibition induced by FTG stimulation was significantly reduced by KA lesioning of the ipsilateral NA or DMV. Subsequently, a bilateral KA lesion of NA or DMV abolished the cardioinhibitory responses of FTG. Compared to the consequence of KA lesion of the DMV, only a smaller bradycardia was induced by FTG stimulation after KA lesion of the NA. The pressor response induced by Glu stimulation of the FTG was reduced by the KA lesion of the CVLM. Such an effect was dominant ipsilaterally. Our findings suggested that both NA and DMV mediated the cardioinhibitory responses of FTG. The pressor message from the FTG neurons might be partly working via a disinhibitory mechanism through the depressor neurons located in the CVLM.     

Effects of Antiepileptic Drug Monotherapy on One-Carbon Metabolism and DNA Methylation in Patients with Epilepsy

Purpose

The aim of this study was to compare the serum levels of one-carbon metabolism (OCM) nutrients (e.g., folate, homocysteine and vitamin B12) and peripheral blood DNA methylation in epileptic patients under treatment with antiepileptic drugs (AEDs) and in healthy controls.

Methods

In this cross-sectional study, 60 patients with epilepsy who were receiving valproate (VPA) (n = 30) or lamotrigine (LTG) (n = 30) monotherapy were enrolled. Thirty age and sex matched healthy subjects served as the controls. Serum concentrations of OCM nutrients and peripheral blood DNA methylation status were measured.

Results

Compared to the control group, the VPA group had higher serum levels of homocysteine (p<0.05). No difference in homocysteine concentration was observed in the LTG group. Patients receiving VPA or LTG had significantly lower serum folate levels in comparison with controls (p<0.001). The level of methylation of long interspersed nucleotide element-1 (LINE-1) in peripheral blood was not significantly different between the AED monotherapy group and healthy controls. A difference in the methylation levels of methylenetetrahydrofolate reductase (MTHFR) amplicon was observed between AED-treated patients with epilepsy and controls (p<0.01). A positive correlation between serum folate levels and peripheral blood MTHFR amplicon methylation status was also observed (r = 0.25, p = 0.023).

Conclusion

Our findings suggest that the effects of AED monotherapy on OCM may induce specific regions of DNA hypomethylation.     

Physical capacity and functional abilities improve in young adults with intellectual disabilities after functional training

Individuals with an intellectual disability (ID) have higher rates of obesity, lower rates of physical activity, cardiorespiratory fitness, and muscular endurance than do typically developed individuals (TDI) and are twice as likely to develop chronic disease, living half as long as TDIs do. The purpose of this study was to examine the improvements in physical capacity and functional ability in Special Olympic Athletes (SOAs) aged 19-22 years after participating in a functional training (FT) program and compare these scores with those of the SOAs in a resistance weight training (WT) program. Twenty SOAs (13 men, 7 women with mild to moderate ID) participated in a 1-hour FT program, twice a week, for 10 weeks, compared with 22 same-aged SOAs (14 men, 8 women) participating in a 1-hour WT program (2× week for 8 weeks). Prefitness and postfitness tests consisting of heart rate (HR) for the 3-minute step test, static plank, body weight squats, static bar hang, and knee push-ups were conducted. Two-tailed, paired sample t-tests (p < 0.05) were used to evaluate the differences in the FT group. Change scores were used to compare FTG with the WT group. The HR decreased by 31.8 b·min?1 pre-post in the FTG (p < 0.001). Static plank duration improved by 22.4 seconds in the FTG (p = 0.016); static plank change scores improved (p = 0.037) for the FTG (26.5 ± 32.1 seconds compared with that for the WT group (4.6 ± 22 seconds). Height and weight values were unchanged in both the groups. The results of this study demonstrate the value of FT programs for this population, because weight equipment is not always available in many settings.     

肝纤维化动物模型探讨

目的 寻找肝纤维化最佳模型.方法 将Wistar大鼠随机分成血清组、四氯化碳皮下注射组、四氯化碳腹腔注射组,每组30只,各组分别给予猪血清腹腔注射、40%四氯化碳皮下和腹腔注射造模(每周2次),观察造模过程中大鼠死亡情况以及4周及6周各组大鼠肝纤维化的程度.结果 3种方法都能成功制备肝纤维化模型.从动物死亡情况来看,四氯化碳腹腔注射组死亡率明显高于前两组;血清组死亡率最低,但与四氯化碳皮下注射组比较无显著差异;从模型形成时间来看,血清组造模时间较长,明显高于其他两组,四氯化碳皮下注射组与四氯化碳腹腔注射组在模型形成时间上无明显差异.结论 四氯化碳皮下注射组制备肝纤维化模型动物死亡率较低,肝纤维化形成时间较短,是一种制作肝纤维化模型较好的方法.     

Optimization of superovulation induction by human menopausal gonadotropin in guinea pigs based on follicular waves and FSH-receptor homologies

The guinea pig represents an excellent animal model for the study of reproduction in humans and most domestic animals because unlike the mouse and rat, it undergoes a complete estrous cycle. In this study, we investigated the availability of ovarian oocytes during the estrous cycle, and the follicle stimulating hormone (FSH) receptor (FSH-R) homologies between guinea pigs and other species, in order to identify an effective gonadotropin and optimal time-of-application for the induction of superovulation in the guinea pig. The number of collectable ovarian oocytes showed biphasic changes with peaks at the midluteal and pre-ovulatory stages. On the other hand, the number of oocytes that matured in vitro remained constant ( approximately 10 oocytes) until day 14 post-ovulation and increased thereafter. The deduced amino acid sequence of the guinea pig FSH-R showed greater similarity to the primate FSH-R than to the rodent FSH-R, which suggests that commercially available human menopausal gonadotropin (hMG) may be a better inducer of superovulation in guinea pigs. Indeed, significantly more oocytes (5.4 +/- 1.6, range 0-17, n = 10) were obtained from hMG-treated guinea pigs at the pre-ovulatory stage than during spontaneous ovulation (3.6 +/- 0.1, n = 96; P < 0.05), whereas guinea pigs that received hMG at the midluteal stage (n = 3) did not ovulate. These results indicate that hMG is an effective, albeit stage-dependent, inducer of superovulation in the guinea pig, and that FSH-R homologies should be taken into account when choosing hormones for superovulation.     

Serum glucose and free fatty acids modulate growth hormone and luteinizing hormone secretion in the pig

Two experiments were conducted to determine the effect of free fatty acids (FFA) and glucose treatment on growth hormone (GH) and luteinizing hormone secretion in the pig. In Experiment (Exp) 1, 15 prepuberal gilts received an intravenous infusion of FFA (n = 5; 3 ml of 10% Liposyn II/kg), glucose (n = 5; 1 g/kg), or saline (n = 5; 3 ml of 0.9%/kg). Jugular blood samples were collected every 15 min for 2 hr before and 3 hr after intravenous infusion of saline, FFA, and glucose. Synthetic [Ala15]-h growth hormone-releasing factor-(1-29)NH2 (1 microgram/kg) and gonadotropin-releasing hormone (0.2 micrograms/kg) were administered 30 min after infusion (Time 0 = infusion). In Exp 2, eight prepuberal gilts received either FFA (n = 4) or saline (n = 4) as described in Exp 1, except that treatments were given every hour ove a 10-hr period. Blood samples were collected every 15 min from 1 hr before to 10 hr after the start of FFA or saline infusion. In Exp 1, the peak GH response to growth hormone-releasing factor was delayed by 45 min (P less than 0.01) by glucose treatment and suppressed (P less than 0.01) by FFA treatment. The luteinizing hormone response to gonadotroph-releasing hormone was suppressed (P less than 0.03) by glucose and enhanced (P less than 0.03) by FFA. In Exp 2, the number of GH pulses was increased (P less than 0.05) by FFA infusion and GH concentrations were positively correlated (r = 0.58, P less than 0.0003) with FFA concentrations, while luteinizing hormone pulse amplitude was greater (P less than 0.01) in FFA gilts than in saline gilts. These results indicate that FFA are more effective modulators of GH secretion than acute hyperglycemia, while metabolic status can alter pituitary responsiveness to gonadotropin-releasing hormone.     

Oestrogen-dependent expression of LH/hCG receptors in pig Fallopian tube and their role in relaxation of the oviduct.

The current studies investigated the concentration and distribution of LH receptors in the oviduct of ovariectomized gilts at various times after administration of oestradiol benzoate (10 micrograms kg-1 body weight) to determine whether LH participates in the regulation of oviductal contractions. Polyclonal antibodies to the LH receptor were used in immunocytochemical and western blot analyses of oviductal tissues. The mechanical activity of the isthmus and ampullar segments of oviduct, collected from 16 cyclic gilts, was recorded for 30 min after LH or hCG treatment. In the oviduct, there was little competition for receptor occupancy between hCG and pig FSH, bovine thyroid-stimulating hormone (TSH), pig growth hormone (GH) and pig prolactin (1.2, 0.1, 0.01 and < 0.001%, respectively) but pig LH could completely inhibit the binding of [125I]hCG. Oestradiol benzoate increased (P < 0.01) the number of LH binding sites in oviduct 24, 48 and 72 h (0.60 +/- 0.08, 1.62 +/- 0.15, 2.48 +/- 0.35 fmol mg-1 protein; n = 4 per treatment, respectively) after injection compared with the control gilts treated with corn oil (0.20 +/- 0.04 fmol mg-1 protein; n = 4). The affinity of oviductal LH/hCG binding sites (Ka) varied from 4.0 to 8.5 x 10(10) l mol-1 and was similar to that of luteal cell binding sites (6.1 x 10(10) l mol-1). Oestradiol benzoate also resulted in more intense LH receptor immunostaining of the tubal mucosal epithelium, smooth muscle cells and blood vessels as compared with controls. Western blotting has revealed that the pig oviduct, similar to the corpus luteum, contains 75, 48 and 45 kDa immunoreactive LH receptor proteins. Treatment with LH in vitro (100 ng ml-1) affected the contractility of oviduct. During the peri-ovulatory stage of the oestrous cycle, the amplitude, frequency and area under curve(s) of the isthmus decreased (P < 0.05), as did the frequency and area under curve (P < 0.05 and P < 0.01, respectively) of the ampulla (n = 4). The frequency and area under curve of the oviductal contractions were also significantly reduced during the early follicular phase of the oestrous cycle (P < 0.05). There was no effect of LH (or hCG) on the frequency and area under curve of the oviductal contractions during luteal stages of the oestrous cycle (n = 8). These data indicate that (1) the pig oviduct possesses immunoreactive and functional LH receptor, (2) oestradiol promotes the synthesis of LH receptor in the epithelium and smooth muscles, and (3) LH causes the relaxation of oviduct, especially during the peri-ovulatory stage of the oestrous cycle. In summary, the results of the present study indicate that LH can control oviductal contractions directly and may be partially responsible for the relaxation of isthmus during fertilization in pigs.     

Natural transmission of Salmonella choleraesuis in swine.

This experiment was designed to study the natural transmission of Salmonella choleraesuis in swine. Forty pigs were divided into three groups. Group 1 (n = 12) was challenged with 10(8) CFU of S. choleraesuis per ml by intranasal inoculation. One day postinoculation (p.i.), group 2 (n = 24) was commingled with group 1. Group 3 (n = 4) served as uninoculated controls. Serum samples were collected weekly. Blastogenesis assays and necropsies were performed at 1, 2, 4, 6, 9, and 12 weeks p.i., and 16 tissue samples per pig were collected and cultured. Environmental (pooled feces from the pen floor) levels of S. choleraesuis were 2.61 log10 CFU/g of feces at 24 h p.i. (immediately prior to commingling). Severe clinical signs were observed in groups 1 and 2. The results indicated that at least 16% of group 2 pigs were shedding S. choleraesuis within 24 h of commingling. At 1 week p.i., 32 of 32 group 1 and 39 of 62 group 2 tissue samples were positive for S. choleraesuis. Only 3 of 12 group 2 pigs were positive at 6, 9, and 12 weeks (1 pig for each week), indicating that only a small proportion of infected swine become long-term carriers. At 12 weeks p.i., only the colon and colonic lymph node samples of one pig from group 2 were positive. Humoral, mucosal, and cellular immune responses were similar between groups 1 and 2. These data demonstrate that a few pigs shedding low levels of Salmonella organisms before slaughter can result in rapid transmission and subsequent shedding by many swine.     

Degradation, receptor binding affinity, and potency of insulin from the Atlantic hagfish (Myxine glutinosa) determined in isolated rat fat cells

Insulin from the Atlantic hagfish, Myxine glutinosa, a primitive vertebrate, was studied with respect to degradation, receptor binding, and stimulation of glucose transport and metabolism in isolated rat adipocytes. The degradation was studied in a concentrated suspension with about 100mul of cells/ml of suspension. 125I-labeled hagfish insulin and 125I-labeled pig insulin were degraded at the same rate when present in concentrations of 0.3nM. Native hagfish insulin inhibited the rate of degradation of 125I-labeled pig insulin half-maximally at a concentration of 12+/-2 nM (S.D., n=6) as compared to 130+/-32 nM (S.D.,n=6) for pig insulin. Native hagfish insulin in a concentration of 130 nM was biologically inactivated at a rate several times slower than pig insulin in the same concentration. The results indicate that the maximal velocity (Vmax) of degradation of hagfish insulin as well as the concentration causing half-maximal velocity (Km) are about 10 times lower for hagfish insulin than for pig insulin. The receptor binding and the biological effects of hagfish insulin were studied in dilute cell suspensions where the degradation of hormone in the medium was negligible. The receptor binding affinity of hagfish insulin was 23+/-7 per cent (S.D., n=10) of that of pig insulin. Hagfish insulin was able to elicit the same maximal stimulation of both 3-o-methylglucose exchange and lipogenesis from glucose as pig insulin. However, the potency of hagfish insulin with respect to activation of lipogenesis was only 4.6+/-0.6 per cent (S.D., n=15) of that of pig insulin. Hagfish insulin thus constitutes the first described insulin which exhibits a discrepancy between relative binding affinity and relative potency. This discrepancy was not due to the methionine residue (B31) at the COOH-terminal end of the B chain of hagfish insulin, since removal of this residue caused no marked change in the binding affinity or the potency. The results indicate that the receptor occupancy must be 5 times higher with hagfish insulin than with pig insulin to cause a particular degree of activation of lipogenesis. Hagfish insulin might therefore be characterized as a "partial antagonist" on the receptors. However, it was not possible to demonstrate antagonistic properties of hagfish insulin on the cells. The effect of hagfish insulin plus pig insulin in submaximally stimulating concentrations was additive. Furthermore, the decay of activation of adipocytes after incubation with hagfish insulin followed the same time course as the decay of activation after incubation with pig insulin in a concentration of equal potency. These phenomena are in agreement with the concept that adipocytes possess a large excess of receptors which can mediate the effect of insulin on lipogenesis from glucose.