Hypoglycemic Effect of a Hot-water Extract from Defatted Sesame (Sesamum indicum L.) Seed on the Blood Glucose Level in Genetically Diabetic KK-Ay Mice

Genetically diabetic (type II) KK-A^y mice, male and 5 weeks of age, were divided into one group of 12 mice that were fed on a basal (BAS) diet and three groups of 6 mice each that were fed on the test diets for 4 weeks. Each test diet contained 4.0% of the hot-water extract (HES) from defatted sesame (Sesamum indicum L.) seed, 1.4% of the water eluent fraction (WFH) of HES or 0.7% of the methanol eluent fraction (MFH) of HES from a glass column packed with HP-20 resin. At the end of the feeding period, the BAS group was divided into the MAL and MALH groups which were respectively force-fed with 1 ml per mouse of a 20% maltose solution in water with or without 4.0% HES. The plasma glucose concentration and amount of urinary excreted glucose were lower from the HES and MFH diets than from the BAS and WFH diets. The levels of plasma glucose and serum insulin were lower in the MALH group than in the MAL group. These results indicate that HES and MFH had a reductive effect on the plasma glucose concentration of KK-A^y mice, and this effect is suggested to have been caused by the delayed glucose absorption.     

Development of New Zinc Dithiosemicarbazone Complex for Use as Oral Antidiabetic Agent

The increasing prevalence of diabetes mellitus (DM) worldwide has underscored the urgency of developing an efficient therapeutic agent. Recently, Zn complexes have been attracting attention due to their antidiabetic activity. In this study, we designed and synthesized a new Zn complex, Zn-3,4-heptanedione-bis(N ⁴-methylthiosemicarbazonato) (Zn-HTSM), characterized its physicochemical properties, and examined its antidiabetic activity in KK-A^y type 2 DM model mice. It was demonstrated that Zn-HTSM has adequate lipophilicity for the cellular permeability, shows potent hypoglycemic activity, and improves glucose intolerance in KK-A^y mice. We also analyzed the levels of serum adipokines after continuous oral administration of Zn-HTSM. The level of serum leptin of KK-A^y mice is significantly reduced by the treatment of Zn-HTSM. Nevertheless, the levels of serum insulin and adiponectin were not improved. These data suggested that the Zn-HTSM acts on the leptin metabolism. Our present studies indicate that Zn-HTSM is a candidate oral antidiabetic agent for the treatment of type 2 DM.     

Antidiabetic Effect of Taxifolin in Cultured L6 Myotubes and Type 2 Diabetic Model KK-Ay/Ta Mice with Hyperglycemia and Hyperuricemia

Muscle is the largest tissue in our body and plays an important role in glucose homeostasis and hence diabetes. In the present study, we examined the effects of taxifolin (TXF) on glucose metabolism in cultured L6 muscle cells (myotubes) and in type 2 diabetic (T2D) model KK-A^y/Ta mice. TXF dose-dependently increased glucose uptake (GU) in L6 myotubes under the condition of insulin absence. This increase in GU was partially, but significantly canceled by TXF treatment in combination with either LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), which phosphorylates protein kinase B (Akt) or Compound C, an inhibitor of 5’-adenosine monophosphate-activated protein kinase (AMPK). Furthermore, TXF was demonstrated to activate (=phosphorylate) both Akt and AMPK, and promote glucose transporter 4 (GLUT4) translocation to the plasma membrane from cytosol of L6 myotubes via both PI3K/Akt and AMPK signaling pathways. Based on these in vitro findings, we conducted an in vivo experiment in KK-A^y/Ta mice with hyperglycemia and hyperuricemia. Fasting plasma glucose, insulin, uric acid levels and an index of insulin resistance (HOMA-IR) increased significantly in the T2D model mice compared with normal ones. Such rises in the T2D state were significantly suppressed by oral administration of TXF for four weeks. These results suggest that TXF is a potent antihyperglycemic and antihyperuricemic phytochemical in the T2D state.     

Effects of glucose-containing peritoneal-dialysis solutions on rates of lipogenesis in vivo in the liver, brown and white adipose tissue of chronic uraemic rats.

Chronic uraemic rats had decreased food intake, and this was accompanied by decreased weight of the epididymal fat-pads and interscapular brown adipose tissue. Normal rats whose food intake was restricted to an amount similar to that of the uraemic rats showed similar decreases in weight of the adipose-tissue depots. In addition, the food-restricted rats had decreased liver weight compared with normal or uraemic rats. The basal rate of lipogenesis was decreased in liver and epididymal fat-pads of food-restricted and uraemic rats and in interscapular brown adipose tissue of uraemic rats. Administration of a low-glucose-containing (1.36%) peritoneal-dialysis solution slightly increased lipogenesis in liver of uraemic rats, but had no significant effect in epididymal fat-pads. For brown fat, the rate of lipogenesis was increased in normal, food-restricted and uraemic groups, but the values for the last group were 4-5-fold lower than for the food-restricted or control groups. A high-glucose-containing (3.86%) peritoneal-dialysis solution gave similar rates of lipogenesis in liver, epididymal fat-pads and brown fat of all three groups, but for brown fat moderately uraemic rats showed a considerably lower rate of lipogenesis than did mildly uraemic rats. The basal plasma insulin concentration was lower in the food-restricted (50%) and uraemic (70%) groups than in the control group. The low-glucose peritoneal-dialysis solution increased plasma insulin to control values in the food-restricted rats, but had no significant effect on plasma insulin in the uraemic rats, despite a significant increase in blood glucose in this group. It is concluded that there is an impairment of the lipogenic response to intraperitoneal glucose loads in interscapular brown adipose tissue of uraemic rats, and that this is not due to the accompanying decrease in food intake. The hypoinsulinaemia may be an important factor. The possible relevance of this finding to the obesity observed in some uraemic patients treated by peritoneal dialysis with glucose-containing solutions is discussed.     

Anti-diabetic effect of S-adenosylmethionine and α-glycerophosphocholine in KK-Ay mice

Six-week-old male KK-A^y mice received drinking water with S-adenosylmethionine (SAM), α-glycerophosphocholine (GPC), or SAM+GPC for 10 weeks. The serum glucose of SAM+GPC at 15 weeks old, total cholesterol of GPC at 12 weeks old, and triglyceride of GPC at 15 weeks old and of SAM at 16 weeks old were reduced. SAM+GPC reduced serum leptin and food intake.

Abbreviations: SAM: S-adenosylmethionine; GPC: α-glycerophosphocholine     

An extract of Artemisia dracunculus L. enhances insulin receptor signaling and modulates gene expression in skeletal muscle in KK-A mice

An ethanolic extract of Artemisia dracunculus L. (PMI 5011) has been observed to decrease glucose and insulin levels in animal models, but the cellular mechanisms by which insulin action is enhanced in vivo are not precisely known. In this study, we evaluated the effects of PMI 5011 to modulate gene expression and cellular signaling through the insulin receptor in skeletal muscle of KK-A^y mice. Eighteen male KK-A^y mice were randomized to a diet (w/w) mixed with PMI 5011 (1%) or diet alone for 8 weeks. Food intake, adiposity, glucose and insulin were assessed over the study, and at study completion, vastus lateralis muscle was obtained to assess insulin signaling parameters and gene expression. Animals randomized to PMI 5011 were shown to have enhanced insulin sensitivity and increased insulin receptor signaling, i.e., IRS-associated PI-3 kinase activity, Akt-1 activity and Akt phosphorylation, in skeletal muscle when compared to control animals (P<.01, P<.01 and P<.001, respectively). Gene expression for insulin signaling proteins, i.e., IRS-1, PI-3 kinase and Glut-4, was not increased, although a relative increase in protein abundance was noted with PMI 5011 treatment. Gene expression for specific ubiquitin proteins and specific 20S proteasome activity, in addition to skeletal muscle phosphatase activity, i.e., PTP1B activity, was significantly decreased in mice randomized to PMI 5011 relative to control. Thus, the data demonstrate that PMI 5011 increases insulin sensitivity and enhances insulin receptor signaling in an animal model of insulin resistance. PMI 5011 may modulate skeletal muscle protein degradation and phosphatase activity as a possible mode of action.     

Antidiabetic effect of green rooibos (Aspalathus linearis) extract in cultured cells and type 2 diabetic model KK-Ay mice

Previous studies have demonstrated antidiabetic effects for rooibos (Aspalathus linearis) and aspalathin (ASP), one of its main polyphenols. Rooibos, an endemic plant of South Africa, is well-known for its use as herbal tea. Green (‘unfermented’) rooibos has been shown to contain more ASP than ‘fermented’ rooibos tea, currently the major product. In the present study, we investigated the antidiabetic effect of green rooibos extract (GRE) through studies on glucose uptake in L6 myotubes and on pancreatic β-cell protective ability from reactive oxygen species (ROS) in RIN-5F cells. Its in vivo effect was also examined using obese diabetic KK-A^y mice. GRE increased glucose uptake under insulin absent condition and induced phosphorylation of 5′-adenosine monophosphate-activated protein kinase (AMPK) in L6 myotubes as previously demonstrated for ASP. In addition to AMPK, GRE also promoted phosphorylation of Akt, another promoter of glucose transporter 4 (GLUT4) translocation, in L6 myotubes unlike ASP, suggesting an involvement of GRE component(s) other than ASP in Akt phosphorylation. Promotion of GLUT4 translocation to the plasma membrane by GRE in L6 myotubes was demonstrated by Western blotting analysis. GRE suppressed the advanced glycation end products (AGEs)-induced increase in ROS levels in RIN-5F pancreatic β-cells. Subchronic feeding with GRE suppressed the increase in fasting blood glucose levels in type 2 diabetic model KK-A^y mice. These in vitro and in vivo results strongly suggest that GRE has antidiabetic potential through multiple modes of action.     

组方食品对2型糖尿病小鼠血糖及 肠道菌群的影响

目的研究含有浒苔等植物的功能性食品对糖尿病小鼠血糖浓度的影响,并应用PCR-DGGE技术评价其对昆明小鼠肠道菌群稳态的影响。方法采用高脂饲料喂养昆明小鼠加腹腔注射链脲佐菌素(STZ)的方法建立糖尿病小鼠模型;将实验动物随机分为正常对照组、自然恢复组和功能性食品喂养组,连续给药4周,尾静脉采血测量血糖水平。收集小鼠新鲜粪便,提取粪便细菌基因组DNA,通过PCR-DGGE获得细菌群落指纹图谱,并进行相关软件分析,同时切离差异显著条带进行序列分析。结果本实验采用的功能性食品对糖尿病小鼠有降糖作用,并使血糖值稳定地维持在较低水平。4周后,功能性食品喂养的糖尿病小鼠血糖水平相对普通饲料喂养的糖尿病小鼠血糖发生显著性下降(t=4.19,P0.01);给2型糖尿病小鼠提供普通饲料时,其肠道菌群种类和数目相对较少;而提供功能性食品时,肠道菌群种类和数目相对增多,特别是双歧杆菌、Prevotella oryzae、Barnesiella intestinihominis、Culturomica和Parabacteroides distasonis明显增多,但是Muribaculum较少。结论高脂饲料结合STZ诱导的2型糖尿病小鼠肠道菌群发生显著改变,组方食品通过扶持肠道菌群,降低血糖水平。     

Increased sperm abnormalities due to dietary restriction

The effect of dietary restriction on sperm-head morphology in BDF₁ mice was studied. The food intake of the ice was restricted to 2.0 or 1.5 g/day during the whole experimental period, while control animals were fed ad libitum. The average food intake of control mice was 4.2 ± 0.5 g/day. The frequencies of abnormal sperm in food-restricted mice remained at the basal level for the first 2 weeks. In week 3, the frequencies of abnormal sperm increased only in mice on the severely restricted diet (1.5 g/day). In week 5, the frequencies of abnormal sperm increased significantly in both restricted groups, and a negative correlation between the food intake and the frequency of abnormal sperm was observed. These results suggest that sperm abnormalities are not always the results of exogenous mutagen-induced damage     

Reduced serotonin reuptake transporter (SERT) function causes insulin resistance and hepatic steatosis independent of food intake

Serotonin reuptake transporter (SERT) is a key regulator of serotonin neurotransmission and a major target of antidepressants. Antidepressants, such as selectively serotonin reuptake inhibitors (SSRIs), that block SERT function are known to affect food intake and body weight. Here, we provide genetic evidence that food intake and metabolism are regulated by separable mechanisms of SERT function. SERT-deficient mice ate less during both normal diet and high fat diet feeding. The reduced food intake was accompanied with markedly elevated plasma leptin levels. Despite reduced food intake, SERT-deficient mice exhibited glucose intolerance and insulin resistance, and progressively developed obesity and hepatic steatosis. Several lines of evidence indicate that the metabolic deficits of SERT-deficient mice are attributable to reduced insulin-sensitivity in peripheral tissues. First, SERT-deficient mice exhibited beta-cell hyperplasia and islet-mass expansion. Second, biochemical analyses revealed constitutively elevated JNK activity and diminished insulin-induced AKT activation in the liver of SERT-deficient mice. SERT-deficient mice exhibited hyper-JNK activity and hyperinsulinemia prior to the development of obesity. Third, enhancing AKT signaling by PTEN deficiency corrected glucose tolerance in SERT-deficient mice. These findings have potential implications for designing selective SERT drugs for weight control and the treatment of metabolic syndromes.     

SGK1 抑制剂改善糖代谢紊乱的作用研究

目的:观察血清和糖皮质激素诱导的蛋白激酶1(serum and glucocorticoid-induced protein kinase1,SGK1)抑制剂对db/db小鼠糖代谢紊乱的改善作用,初步探讨该作用是否与改善脂肪组织功能紊乱有关。方法:将db/db小鼠随机分为db/db组、抑制剂组,同时设db/m组,db/db组、db/m组小鼠给予普通饲料喂养,抑制剂组小鼠给予含SGK1抑制剂的饲料喂养,干预8周。观察体重、摄食量、空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(glycosylated hemoglobin,Hb A1C),干预8周后行腹腔葡萄糖耐量试验(intraperitoneal glucose tolerance test,IPGTT)、腹腔胰岛素耐量试验(intraperitoneal insulin tolerance test,IPITT)。酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测血清空腹胰岛素(fasting insulin,FINS)水平,计算胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)及胰岛素敏感性指数(insulin sensitivity index,ISI)。实时定量荧光PCR(real-time PCR)法检测脂肪组织中SGK1、脂肪细胞因子m RNA表达水平。结果:干预8周后,抑制剂组体重、FBG、Hb A1C、IPGTT、IPITT均低于db/db组(P0.05),摄食量无明显差异。与db/db组相比,抑制剂组血清FINS有下降趋势,HOMA-IR明显降低,ISI明显升高(P0.05)。SGK1抑制剂干预治疗后,脂肪组织中SGK1、单核细胞趋化因子-1(monocyte chemotactic protein-1,MCP-1)、凝血酶元激活因子的抑制因子-1(plasminogen activator inhibitor 1,PAI-1)m RNA表达下降(P0.05),脂联素(adiponectin)m RNA表达无明显变化。结论:SGK1抑制剂干预治疗可一定程度改善db/db小鼠糖代谢紊乱,该作用可能部分与改善脂肪组织功能紊乱有关。     

链脲佐菌素诱导C57小鼠1型糖尿病模型的研究

目的:通过小剂量多次腹腔注射链脲佐菌素(STZ)诱导建立与人类1型糖尿病相似的C57小鼠糖尿病模型,研究建模剂量和成模率。方法:将32只C57小鼠随机分为正常对照组(A)和实验组(B)。实验组(B)可分为低、中、高剂量组(50 mg/kg、70mg/kg、90 mg/kg)(n=8)。两组都喂普通饲料1周后,B组连续5天腹腔注射不同剂量STZ,测定注射前、注射后1周、2周、3周、4周、5周的空腹血糖和体重,观察小鼠饮食、饮水和排尿情况。STZ注射第3周进行口服糖耐量实验(OGTT)。结果:给药前A、B组体重和血糖无显著差异,给药1周后,B组饮水量和进食量明显增加,体重减轻。C57小鼠用药2周后,中剂量组达到建模标准,成模率75%。各剂量组均出现了糖耐量异常。结论:诱导建立C57小鼠1型糖尿病模型方法是连续5日腹腔注注射STZ,适宜剂量为70 mg/kg。     

Protective Effects of Moderate Intensity Static Magnetic Fields on Diabetic Mice

The purpose of this study was to investigate the effects of moderate-intensity static magnetic field (SMF) on diabetic mice. We studied the effects of SMF on blood glucose of normal mice by starch tolerance and glucose tolerance tests. Then, we evaluated the effects of SMF on blood glucose of diabetic mice by establishing alloxan-induced type 1 diabetic mice and high-fat diet + streptozotocin (STZ)-induced type 2 diabetic mice. The results showed that different magnetic field intensities and blank control did not affect the blood glucose of normal mice. After starch and glucose administration, different magnetic fields could improve the glucose tolerance of normal mice, and this was obvious in the 600 mT group. In the experiment of type 1 diabetic mice induced by alloxan, the results showed that different magnetic field intensities could improve the starch tolerance of mice, and that in the 400 mT group was obvious. In the experiment of type 2 diabetic mice induced by a high-fat diet + STZ, the 400 mT group could reduce food intake and water consumption in the later period. The 600 mT group could improve the starch tolerance of mice. The 400 and 600 mT groups could reduce fasting blood glucose. At the same time, total cholesterol and triglyceride decreased in different magnetic field intensities, and the 600 mT group could significantly increase the serum insulin content of mice. In summary, the results of this study suggest that SMF has a protective role in diabetic mice. Bioelectromagnetics. © 2020 Bioelectromagnetics Society     

大黄素降糖及改善脂质代谢的实验研究

目的：探讨大黄素对2型糖尿病模型db/db小鼠血糖及血脂水平的影响。方法：4周龄16只db/db雄性小鼠随机分为治疗组和对照组,每组8只;治疗组经灌胃每天给予100mg/kg大黄素;对照组灌胃给予相仿体积的生理盐水,开始10天每天算进食量,每周测空腹血糖及体重1次,连续干预8周,干预前及实验结束前1周测胰岛素耐量,干预结束后于颈动脉取血测血脂水平（HDL-C、LDL-C、TG、TC）。结果：①大黄素干预不影响db/db小鼠的进食量,与对照组比较,P〉0.05;②大黄素可显著减轻db/db小鼠体重,与对照组比较,P〈0.05;③大黄素可改善db/db小鼠胰岛素敏感性,降低小鼠的空腹血糖水平,与对照组比较,P〈0.05或P〈0.01;④大黄素可降低db/db小鼠血TG、TC、LDL-C水平,P〈0.01。结论：大黄素可有效地改善db/db小鼠的糖脂紊乱状态,其降糖及改善血脂代谢机制值得进一步深入研究。     

Guar gum consumption in adolescent and adult rats: short- and long-term metabolic effects

Metabolic responses to short- and long-term guar gum consumption were studied in adolescent and adult rats. For the long-term study, male adolescent rats were divided into four groups (n = 60/group) and fed guar gum, cellulose, or bran diet for 67 weeks. Metabolic studies (food--water intake, feces--urine output, body weight, carbohydrate tolerance) were performed eight times during the 67 weeks. The guar gum group consumed less diet throughout the entire study and gained less weight over the first 20 weeks compared with the cellulose and bran groups. A second bran-fed group was food restricted over the first 20 weeks to match the reduced weight gain of the guar gum group and then fed ad libitum. Reduced plasma glucose excursions were measured for only the guar gum group after both fibre-free glucose and sucrose challenges at weeks 6, 12, and 18; from 24 to 64 weeks all four groups had similar glucose tolerance responses. Twenty-four hour urinary glucose excretion was similar during all eight metabolic studies up to 64 weeks for guar gum and cellulose groups. In the short-term study, male adolescent (200 g; n = 10/group) and adult (630 g; n = 15/group) rats were divided into five and four groups, respectively, and fed guar gum, guar by-product (GBP), cellulose, or bran diet for 6 weeks. A metabolic study was performed during the 6th week. Adolescent rats fed guar gum or GBP diets gained less weight than the cellulose group; only the guar gum group displayed improved carbohydrate tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood

Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD. Body composition, energy expenditure, food intake and leptin levels were analyzed in adult offspring. Blood glucose and plasma insulin concentrations were measured before and during a glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma leptin and insulin concentrations compared to controls. EFAD offspring fed HFD were resistant to diet-induced obesity, had higher energy expenditure and lower levels of plasma leptin and insulin compared to controls. These results indicate that the fatty acid composition during lactation is important for body composition and glucose tolerance in the adult offspring.     

Hypoglycemic effects of MDG-1, a polysaccharide derived from Ophiopogon japonicas, in the ob/ob mouse model of type 2 diabetes mellitus

Ophiopogon japonicus is a traditional Chinese medicine used to treat diabetes mellitus. We investigate the anti-ischemic properties of a water-soluble β-d-fructan (MDG-1) from O. japonicus, and assess the antidiabetic effects of MDG-1. In the study, ob/ob mice were treated with 150 mg/kg or 300 mg/kg MDG-1 by gavage for 23 d. Blood glucose levels were measured regularly. An oral glucose tolerance test (OGTT) was preformed on day 21. The levels of insulin, total cholesterol and triglyceride in the serum were measured at the end of administration. The liver triglyceride content and tissue weights were also determined. Results show that MDG-1 (300 mg/kg) was demonstrated to exert acute and long-term hypoglycemic effects on fed blood glucose in ob/ob mice. However, only a marginal hypoglycemic effect on fasting blood glucose levels was observed. MDG-1 (300 mg/kg) improved oral glucose tolerance and reduced serum insulin levels and triglyceride content in the liver in ob/ob mice. Furthermore, a reduction in body weight gain and the weight of subcutaneous fat were observed following treatment with MDG-1 (150 mg/kg) compared with the control group. MDG-1 had no significant effects on the total cholesterol and triglyceride levels, food intake and other adipose and organ tissues. These data suggest that MDG-1 exhibits hypoglycemic activity and reduces insulin resistance.     

Moderately high intake of folic acid has a negative impact on mouse embryonic development

BACKGROUND

The incidence of neural tube defects has diminished considerably since the implementation of food fortification with folic acid (FA). However, the impact of excess FA intake, particularly during pregnancy, requires investigation. In a recent study, we reported that a diet supplemented with 20‐fold higher FA than the recommended intake for rodents had adverse effects on embryonic mouse development at embryonic days (E)10.5 and 14.5. In this report, we examined developmental outcomes in E14.5 embryos after administering a diet supplemented with 10‐fold higher FA than recommended to pregnant mice with and without a mild deficiency of methylenetetrahydrofolate reductase (MTHFR).

METHODS

Pregnant mice with or without a deficiency in MTHFR were fed a control diet (recommended FA intake of 2 mg/kg diet for rodents) or an FA‐supplemented diet (FASD; 10‐fold higher than the recommended intake [20 mg/kg diet]). At E14.5, mice were examined for embryonic loss and growth retardation, and hearts were assessed for defects and for ventricular wall thickness.

RESULTS

Maternal FA supplementation was associated with embryonic loss, embryonic delays, a higher incidence of ventricular septal defects, and thinner left and right ventricular walls, compared to mothers fed control diet.

CONCLUSIONS

Our work suggests that even moderately high levels of FA supplementation may adversely affect fetal mouse development. Additional studies are warranted to evaluate the impact of high folate intake in pregnant women. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.     

Hypoglycemic activity of Eriobotrya japonica seeds in type 2 diabetic rats and mice

The hypoglycemic effects of Eriobotrya japonica seeds were investigated in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and KK-A(y) mice. The rats and mice were fed on a diet containing 10% powdered Eriobotrya japonica seeds with the coat intact for 4 months. Although the blood glucose concentration in the OLETF rats fed on the control diet without Eriobotrya japonica seeds was increased with time, the concentration in the OLETF rats fed on the diet with Eriobotrya japonica seeds was consistently low throughout the experimental period and was comparable to the level in Long-Evans Tokushima Otsuka (LETO) rats which are normal non-diabetic rats. Serum insulin was significantly lower in the OLETF rats fed on the Eriobotrya japonica seed diet than in those fed on the control diet at the termination of the experimental period. Eriobotrya japonica seeds suppressed the increment of blood glucose for 4 months and also effectively improved the glucose tolerance in the KK-A(y) mice, these actions being mainly exerted by the ethanol extract of the seeds. These results suggest that Eriobotrya japonica seeds had a hypoglycemic property and the effect is attributable to the components extracted by ethanol.