Differential expression and localization of neuropeptide Y peptide in pancreatic islet of diabetic and high fat fed rats

Neuropeptide Y (NPY) inhibits insulin secretion. Increased numbers of pancreatic islet cells expressing NPY have been observed in type 1 diabetic rats. To understand the functional significance of NPY expression in islet cells, we investigated the effects of high fat feeding and diabetic conditions on the expression and location of NPY expressing cells in normal and diabetic rats. Twenty rats were maintained on either normal chow (ND) or a high fat dietary regimen (HFD) for 4 weeks. In half of each group, type 1 or type 2 diabetes (groups T1DM and T2DM, respectively) was induced by injection of streptozotocin. At 8 weeks rats were euthanized and the pancreases were processed for immunofluorescence labeling (NPY/insulin, NPY/glucagon, NPY/somatostatin, and NPY/pancreatic polypeptide). Compared with the ND group, HFD rats had significantly fewer alpha cells, but beta cells were similar, while T1DM and T2DM rats showed significant increases in the proportions of alpha, delta, and PP cells. Robust increases in NPY-positive islet cells were found in the HFD, T1DM, and T2DM rats compared with ND controls. In ND rats, 99.7% of the NPY-positive cells were PP cells. However, high fat feeding and diabetes resulted in significant increases in NPY-positive delta cells, with concomitant decreases in NPY-positive PP cells. In summary, high-fat feeding and diabetes resulted in changes in the hormonal composition of pancreatic islet and increased number of NPY-expressing islet cells. Under diabetic conditions NPY expression switched from predominantly a characteristic of PP cells to predominantly that of delta cells. This may be a factor in reduced pancreatic hormone secretion during diabetes.     

Differentially expressed proteins in the pancreas of diet-induced diabetic mice

The pancreas is a heterogeneous organ mixed with both exocrine and endocrine cells. The pancreas is involved in metabolic activities with the endocrine cells participating in the regulation of blood glucose, while the exocrine portion provides a compatible environment for the pancreatic islets and is responsible for secretion of digestive enzymes. The purpose of this study was to identify pancreatic proteins that are differentially expressed in normal mice and those with diet-induced type 2 diabetes (T2DM). In this study, C57BL/6J male mice fed a high fat diet became obese and developed T2DM. The pancreatic protein profiles were compared between control and diabetic mice using two-dimensional gel electrophoresis. Differentially expressed protein "spots" were identified by mass spectrometry. REG1 and REG2 proteins, which may be involved in the proliferation of pancreatic beta cells, were up-regulated very early in the progression of obese mice to T2DM. Glutathione peroxidase, which functions in the clearance of reactive oxidative species, was found to be down-regulated in the diabetic mice at later stages. The RNA levels encoding REG2 and glutathione peroxidase were compared by Northern blot analysis and were consistent to the changes in protein levels between diabetic and control mice. The up-regulation of REG1 and REG2 suggests the effort of the pancreas in trying to ameliorate the hyperglycemic condition by stimulating the proliferation of pancreatic beta cells and enhancing the subsequent insulin secretion. The down-regulation of glutathione peroxidase in pancreas could contribute to the progressive deterioration of beta cell function due to the hyperglycemia-induced oxidative stress.     

Relationship between pancreatic vesicular monoamine transporter 2 (VMAT2) and insulin expression in human pancreas

Vesicular monoamine transporter 2 (VMAT2) is expressed in pancreatic beta cells and has recently been proposed as a target for measurement of beta cell mass in vivo. We questioned, (1) What proportion of beta cells express VMAT2? (2) Is VMAT2 expressed by other pancreatic endocrine or non-endocrine cells? (3) Is the relationship between VMAT2 and insulin expression disturbed in type 1 (T1DM) or type 2 diabetes (T2DM)? Human pancreas (7 non-diabetics, 5 T2DM, 10 T1DM) was immunostained for insulin, VMAT2 and other pancreatic hormones. Most beta cells expressed VMAT2. VMAT2 expression was not changed by the presence of diabetes. In tail of pancreas VMAT2 immunostaining closely correlated with insulin staining. However, VMAT2 was also expressed in some pancreatic polypeptide (PP) cells. Although VMAT2 was not excluded as a target for beta cell mass measurement, expression of VMAT2 in PP cells predicts residual VMAT2 expression in human pancreas even in the absence of beta cells.     

Response of rat exocrine pancreas to high-fat and high-carbohydrate diets

Intake of diets with high fat content is a risk factor for acute pancreatitis and pancreatic cancer. The underlying mechanisms leading to the development of these diseases due to high fat intake are currently unknown. The current study was designed in rats to determine the physiologic and pathological consequences of a highfat diet that contained excess amounts of cottonseed oil or a high-carbohydrate diet that contained high amounts of sucrose on the exocrine pancreas. Rats were maintained on the diets for 4 weeks, and a cannula was inserted into the right jugular vein and one into the pancreatic duct for collection of pancreatic juice. Volume of the pancreatic juice and concentrations of amylase, lipase, and trypsinogen in the pancreatic juice were measured before and after infusions of CCK-8. Results showed that basal and CCK-stimulated pancreatic outputs of volume, amylase and lipase but not trypsinogen, were significantly elevated in intact rats given a high-fat diet when compared with rats given a high-carbohydrate diet. Forty-eight hours later, rats were sacrificed, and parts of the pancreas were removed for isolation of pancreatic acinar cells and for histopathologic studies. Pancreatic acini isolated from rats on a high-fat diet showed significantly lower basal and CCK-stimulated amylase release when compared with those on a high-carbohydrate diet. Histology of the pancreas of rats on a high-carbohydrate diet appeared normal; however, the pancreas of rats on high-fat diet showed significant alterations in exocrine pancreas. These results showed abnormalities in the exocrine pancreas of rats on a high-fat diet, that were not found in rats on a high-carbohydrate diet; further, they support the contention that a high-fat diet has a deleterious effect on the pancreas.     

Effect of replacing grass silage with maize silage in the diet on bovine milk fatty acid composition

Even though extensive research has examined the role of nutrition on milk fat composition, there is less information on the impact of forages on milk fatty acid (FA) composition. In the current study, the effect of replacing grass silage (GS) with maize silage (MS) as part of a total mixed ration on animal performance and milk FA composition was examined using eight multiparous mid-lactation cows in a replicated 4 × 4 Latin square with 28-day experimental periods. Four treatments comprised the stepwise replacement of GS with MS (0, 160, 334 and 500 g/kg dry matter (DM)) in diets containing a 54 : 46 forage : concentrate ratio on a DM basis. Replacing GS with MS increased (P < 0.001) the DM intake, milk yield and milk protein content. Incremental replacement of GS with MS in the diet enhanced linearly (P < 0.001) the proportions of 6:0-14:0, decreased (P < 0.01) the 16:0 concentrations, but had no effect on the total milk fat saturated fatty acid content. Inclusion of MS altered the distribution of trans-18:1 isomers and enhanced (P < 0.05) total trans monounsaturated fatty acid and total conjugated linoleic acid content. Milk total n-3 polyunsaturated fatty acid (PUFA) content decreased with higher amounts of MS in the diet and n-6 PUFA concentration increased, leading to an elevated n-6 : n-3 PUFA ratio. Despite some beneficial changes associated with the replacement of GS with MS, the overall effects on milk FA composition would not be expected to substantially improve long-term human health. However, the role of forages on milk fat composition must also be balanced against the increases in total milk and protein yield on diets containing higher proportions of MS.     

实验性2型糖尿病心肌病大鼠模型的建立与评价

目的建立和评价2型糖尿病心肌病（DC）大鼠模型,探究高糖脂饮食在模型建立中的作用。方法将雄性Wistar大鼠随机分成正常对照组、高糖脂饮食组和高糖脂负荷小剂量STZ组。高糖高脂膳食诱导11周负荷小剂量链脲佐菌素（STZ）（30 mg/kg）腹腔注射建立DC模型,并观察糖代谢、脂代谢和心功能的变化。结果①大鼠经高糖高脂饲料诱导4周后,与正常对照组相比,胆固醇（TCH）和甘油三酯（TG）均显著增高（P〈0.05）,血糖值没有明显变化（P〉0.05）。②大鼠注射30 mg/kg STZ后72 h,血糖水平开始升高,继续以高糖高脂饲料喂养6周后,与正常对照组比较,高糖脂饮食组和高糖脂负荷小剂量STZ组大鼠TG、TCH维持高水平,差异有显著性（P〈0.05）;高糖脂负荷小剂量STZ组大鼠血糖值持续高水平,与正常对照组差异有显著性（P〈0.001）。③心功能测量结果显示,高糖脂饮食组大鼠出现温和的心脏功能异常（左心室收缩压降低,左心室舒张末压升高）;高糖脂负荷小剂量STZ组大鼠左心室收缩和舒张功能均出现异常（LVSP、每搏输出量、心排量降低,LVEDP、左心室最大舒张速率升高）,但以舒张功能异常为主。结论大鼠高糖脂饮食诱导负荷小剂量STZ可建立类似临床症状的2型DC模型,高糖脂饮食在糖脂代谢紊乱和心脏功能损伤过程中有重要作用,结合糖、脂代谢指标和心脏功能指标可以有效简便评价糖尿病心肌病模型。     

Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells.

apoE-deficient mice have been created by homologous recombination in ES cells. On a low fat, low cholesterol chow diet these animals have plasma cholesterol levels of 494 mg/dl compared with 60 mg/dl in control animals, and when challenged with a high fat Western-type diet, these animals have plasma cholesterol levels of 1821 mg/dl compared with 132 mg/dl in controls. This marked hypercholesterolemia is primarily due to elevated levels of very low and intermediate density lipoproteins. At 10 weeks of age, apoE-deficient mice have already developed atherosclerotic lesions in the aorta and coronary and pulmonary arteries. apoE-deficient mice are a promising small animal model to help understand the role of apoE in vivo and the genetic and environmental determinants of atherosclerosis.     

Antioxidant treatment may protect pancreatic beta cells through the attenuation of islet fibrosis in an animal model of type 2 diabetes

Islet fibrosis could be important in the progression of pancreatic beta cell failure in type 2 diabetes. It is known that oxidative stress is involved in the pancreatic fibrosis through the activation of pancreatic stellate cells. However, no study has investigated the in vivo effects of antioxidants on islet fibrogenesis in type 2 diabetes. In this study, antioxidants (taurine or tempol) were administered in drinking water to Otsuka Long-Evans Tokushima Fatty rats, an animal model of type 2 diabetes, for 16 weeks. An intraperitoneal glucose tolerance test revealed that the blood glucose levels after the glucose injection were decreased by the antioxidants. The insulin secretion after the glucose injection, which was markedly reduced in the rats, was also restored by the antioxidants. Beta cell mass and pancreatic insulin content were greater in the rats treated with the antioxidants than in the untreated rats. Beta cell apoptosis was attenuated in the rats by the antioxidants. Finally, islet fibrosis and the activation of pancreatic stellate cells were markedly diminished in the rats by the antioxidants. Our data suggest that antioxidants may protect beta cells through the attenuation of both islet fibrosis and beta cell apoptosis in type 2 diabetes.     

Running Exercise Improves Metabolic Abnormalities and Fat Accumulation in Sucrose-Induced Insulin-Resistant Rats

NARA, MAKOTO, MASAKI TAKAHASHI, TSUGIYASU KANDA, YOUNOSUKE SHIMOMURA, ISAO KOBAYASHI. Running exercise improves metabolic abnormalities and fat accumulation in sucrose-induced insulin-resistant rats. Insulin resistance and hyperinsulinemia are observed in rats fed a high sucrose diet. Insulin resistance is thought to be related to abnormal fat distribution. We previously reported the metabolic characteristics and the fat distribution in rats with sucrose-induced insulin resistance. This study was designed to examine the effects of exercise in these rats. The rats were divided into three groups: those receiving a starch-based diet (control), those receiving a high-sucrose diet (sucrose fed), and those receiving a high-sucrose diet and wheel-running exercise (exercised). Animals were killed after 4 weeks or 12 weeks. After 4 weeks, the three groups did not differ with respect to gain in adipose tissues. The portal vein (PV) insulin concentration was significantly increased in the sucrose-fed and the exercised rats compared with the control rats. The inferior vena cava (IVC) glucose concentration and the PV free fatty acid (FFA) were significantly lower in the exercised rats than in the sucrose-fed rats. After 12 weeks, the exercised rats had significantly lower mesenteric fat (MS) and subcutaneous fat (SC) and a lower MS:SC ratio than the sucrose-fed rats. The glucose levels in IVC, PV, and FFA in PV were significantly reduced in the exercised rats as compared with the sucrose-fed rats. These findings suggest that long-term exercise improves insulin resistance by reducing the accumulation of MS as well as SC. It is also suggested that short-term exercise improves glucose metabolism without change of fat accumulation.     

Diabetes in the Cohen Rat Intensifies the Fetal Pancreatic Damage Induced by the Diabetogenic High Sucrose Low Copper Diet

Intrauterine hyperglycemic environment could harm the fetus making it more susceptible to develop postnatal glucose intolerance. A possible mechanism is compromise of the fetal pancreatic development. We previously found that a high sucrose low copper diabetogenic diet induces type 2 diabetes in the Cohen diabetic sensitive rats, but not in the Sabra control rats. However, oxidative stress was observed in the placenta and term fetal liver of diabetic and nondiabetic controls. We now investigated whether the fetal pancreas is affected by this diet and whether the effects result from oxidative stress, maternal hyperglycemia, or both. Term fetal pancreases were evaluated for morphology, beta cells, oxidative stress, apoptosis, and DNA methylation. There were no microscopic changes in hematoxylin and eosin stained sections and beta cells immunostaining in the pancreas of fetuses of both strains. Fetuses of the sensitive strain fed diabetogenic diet had significantly higher activity of superoxide dismutase and catalase, elevated levels of low molecular weight antioxidants, and more intense immunostaining for nuclear factor kappa‐B and hypoxia inducing factor‐1α. Both strains fed diabetogenic diet had increased immunostaining for Bcl‐2‐like protein and caspase 3 and decreased immunostaining for 5‐methylcytosine in their islets and acini. Our data suggest that maternal diabetogenic diet alters apoptotic rate and epigenetic steady states in the term fetal pancreas, unrelated to maternal diabetes. Maternal hyperglycemia further increases pancreatic oxidative stress, aggravating the pancreatic damage. The diet‐induced insults to the fetal pancreas may be an important contributor to the high susceptibility to develop diabetes following metabolic intrauterine insults     

Differential gene expression in pancreatic tissues of streptozocin-induced diabetic rats and genetically-diabetic mice in response to hypoglycemic dipeptide cyclo (His-Pro) treatment

Diabetic studies are mostly interested in gene expression in the pancreas, the site of insulin secretion that regulates blood glucose levels. However, a single gene approach has been ruled out for many years in discovering new genes or the molecular networks involved in the induction process of diabetes. To understand the molecular mechanisms by which cyclo (His-Pro) (CHP) affects amelioration of diabetes mellitus, we performed gene expression profiling in the pancreatic tissues of two diabetic animal models, streptozocin (STZ)-induced diabetic rats (T1DM) and genetically-diabetic (C57BL/6J ob/ob) mice (T2DM). To understand the healing process of these diabetic rodents, we examined the effects of CHP on various gene expression in pancreatic tissues of both animal models. Our microarray analysis revealed that a total of 1,175 genes were down-regulated and 629 genes were up-regulated in response to STZ treatment, and the altered expression levels of numerous genes were restored to normal state upon CHP treatment. In particular, 476 genes showed significantly altered gene expression upon CHP treatment. In a functional classification, 7,198 genes were counted as differentially expressed in pancreatic tissues of STZ- and CHP-treated rats compared with control, whereas 1,534 genes were restored to normal states by CHP treatment. Microarray data demonstrated for the first time that overexpression of the genes encoding IL-1 receptor, lipid metabolic enzymes (e.g. Mte1, Ptdss1, and Sult2a1), myo-inositol oxygenase, glucagon, and somatostatin as well as down-regulation of olfactory receptor 984 and mitochondrial ribosomal protein, which are highly linked to T1DM etiology. In genetically-diabetic mice, 4,384 genes were altered in gene expression by more than 2-fold compared to the control mice, when counted differentially expressed. In genetically-diabetic mice, 4,384 genes altered in expression by higher than 2-fold were counted as differentially expressed genes in pancreatic tissues of CHP-treated mice. On the other hand, 2,140 genes were up-regulated and 2,244 genes were down-regulated by CHP treatment. The results of the microarray analysis revealed that up-regulation of IL-2, IL12a, and leptin receptor and down-regulation of PIK3 played important physiological roles in the onset of T2DM. In conclusion, we hypothesize that CHP accelerates alterations of gene expression in ameliorating diabetes and antagonizes those that induces the disease.     

Insulin secretory responses and phospholipid composition of pancreatic islets from mice that do not express Group VIA phospholipase A2 and effects of metabolic stress on glucose homeostasis

Studies involving pharmacologic or molecular biologic manipulation of Group VIA phospholipase A(2) (iPLA(2)beta) activity in pancreatic islets and insulinoma cells suggest that iPLA(2)beta participates in insulin secretion. It has also been suggested that iPLA(2)beta is a housekeeping enzyme that regulates cell 2-lysophosphatidylcholine (LPC) levels and arachidonate incorporation into phosphatidylcholine (PC). We have generated iPLA(2)beta-null mice by homologous recombination and have reported that they exhibit reduced male fertility and defective motility of spermatozoa. Here we report that pancreatic islets from iPLA(2)beta-null mice have impaired insulin secretory responses to D-glucose and forskolin. Electrospray ionization mass spectrometric analyses indicate that the abundance of arachidonate-containing PC species of islets, brain, and other tissues from iPLA(2)beta-null mice is virtually identical to that of wild-type mice, and no iPLA(2)beta mRNA was observed in any tissue from iPLA(2)beta-null mice at any age. Despite the insulin secretory abnormalities of isolated islets, fasting and fed blood glucose concentrations of iPLA(2)beta-null and wild-type mice are essentially identical under normal circumstances, but iPLA(2)beta-null mice develop more severe hyperglycemia than wild-type mice after administration of multiple low doses of the beta-cell toxin streptozotocin, suggesting an impaired islet secretory reserve. A high fat diet also induces more severe glucose intolerance in iPLA(2)beta-null mice than in wild-type mice, but PLA(2)beta-null mice have greater responsiveness to exogenous insulin than do wild-type mice fed a high fat diet. These and previous findings thus indicate that iPLA(2)beta-null mice exhibit phenotypic abnormalities in pancreatic islets in addition to testes and macrophages.     

Pancreatic insulin secretion in rats fed a soy protein high fat diet depends on the interaction between the amino acid pattern and isoflavones

Obesity is frequently associated with the consumption of high carbohydrate/fat diets leading to hyperinsulinemia. We have demonstrated that soy protein (SP) reduces hyperinsulinemia, but it is unclear by which mechanism. Thus, the purpose of the present work was to establish whether SP stimulates insulin secretion to a lower extent and/or reduces insulin resistance, and to understand its molecular mechanism of action in pancreatic islets of rats with diet-induced obesity. Long-term consumption of SP in a high fat (HF) diet significantly decreased serum glucose, free fatty acids, leptin, and the insulin:glucagon ratio compared with animals fed a casein HF diet. Hyperglycemic clamps indicated that SP stimulated insulin secretion to a lower extent despite HF consumption. Furthermore, there was lower pancreatic islet area and insulin, SREBP-1, PPARgamma, and GLUT-2 mRNA abundance in comparison with rats fed the casein HF diet. Euglycemic-hyperinsulinemic clamps showed that the SP diet prevented insulin resistance despite consumption of a HF diet. Incubation of pancreatic islets with isoflavones reduced insulin secretion and expression of PPARgamma. Addition of amino acids resembling the plasma concentration of rats fed casein stimulated insulin secretion; a response that was reduced by the presence of isoflavones, whereas the amino acid pattern resembling the plasma concentration of rats fed SP barely stimulated insulin release. Infusion of isoflavones during the hyperglycemic clamps did not stimulate insulin secretion. Therefore, isoflavones as well as the amino acid pattern seen after SP consumption stimulated insulin secretion to a lower extent, decreasing PPARgamma, GLUT-2, and SREBP-1 expression, and ameliorating hyperinsulinemia observed during obesity.     

Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI

Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x10⁶, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in T2DM rats significantly (p<0.05) decreased blood-brain barrier disruption starting at 1 week post stroke measured using contrast enhanced T₁-weighted imaging with gadopentetate, and reduced cerebral hemorrhagic spots starting at 3 weeks post stroke measured using susceptibility weighted imaging, although BMSC treatment did not reduce the ischemic lesion volumes as demarcated by T₂ maps. These MRI measurements were consistent with histological data. Thus, BMSC treatment of stroke in T2DM rats initiated at 3 days after stroke significantly reduced ischemic vascular damage, although BMSC treatment did not change infarction volume in T2DM rats, measured by MRI.     

A Model of Metabolic Syndrome and Related Diseases with Intestinal Endotoxemia in Rats Fed a High Fat and High Sucrose Diet

Aim

We sought develop and characterize a diet-induced model of metabolic syndrome and its related diseases.

Methods

The experimental animals (Spague-Dawley rats) were randomly divided into two groups, and each group was fed a different feed for 48 weeks as follows: 1) standard control diet (SC), and 2) a high sucrose and high fat diet (HSHF). The blood, small intestine, liver, pancreas, and adipose tissues were sampled for analysis and characterization.

Results

Typical metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD), and type II diabetes (T2DM) were common in the HSHF group after a 48 week feeding period. The rats fed HSHF exhibited signs of obesity, dyslipidemia, hyperglycaemia, glucose intolerance, and insulin resistance (IR). At the same time, these animals had significantly increased levels of circulating LPS, TNFα, and IL-6 and increased ALP in their intestinal tissue homogenates. These animals also showed a significant reduction in the expression of occluding protein. The HSHF rats showed fatty degeneration, inflammation, fibrosis, cirrhosis, and lipid accumulation when their liver pathologies were examined. The HSHF rats also displayed increased islet diameters from 12 to 24 weeks, while reduced islet diameters occurred from 36 to 48 weeks with inflammatory cell infiltration and islet fat deposition. The morphometry of adipocytes in HSHF rats showed hypertrophy and inflammatory cell infiltration. HSHF CD68 analysis showed macrophage infiltration and significant increases in fat and pancreas size. HSHF Tunel analysis showed significant increases in liver and pancreas cell apoptosis.

Conclusions

This work demonstrated the following: 1) a characteristic rat model of metabolic syndrome (MS) can be induced by a high sucrose and high fat diet, 2) this model can be used to research metabolic syndrome and its related diseases, such as NAFLD and T2DM, and 3) intestinal endotoxemia (IETM) may play an important role in the pathogenesis of MS and related diseases, such as NAFLD and T2DM.     

Dietary fish oil reverse epididymal tissue adiposity, cell hypertrophy and insulin resistance in dyslipemic sucrose fed rat model small star, filled

The present work was designed to assess the possible benefits of (7% w/w) dietary fish oil in reversing the morphological and metabolic changes present in the adipose tissue of rats fed an SRD for a long time. With this purpose, in the epididymal fat tissue, we investigated the effect of dietary fish oil upon: i) the number, size and distribution of cells, ii) the basal and stimulated lipolysis, iii) the lipoprotein lipase (LPL) and the glucose 6-phosphate dehydrogenase activities, and iv) the antilipolytic action of insulin. The study was conducted on rats fed an SRD during 120 days with fish oil being isocaloric substituted for corn oil for 90-120 days in half the animals. Permanent hypertriglyceridemia, insulin resistance and abnormal glucose homeostasis were present in the rats before the source of fat in the diet was replaced. The major new findings of this study are the following: i) Dietary fish oil markedly reduced the fat pads mass, the hypertrophy of fat cells and improved the altered cell size distribution. ii) The presence of fish oil in the diet corrected the inhibitory effect of high sucrose diet upon the antilipolytic action of insulin, reduced the "in vitro" enhanced basal lipolysis and normalized isoproterenol-stimulated lipolysis. Fat pads lipoprotein lipase activity decreased reaching values similar to those observed in age-matched controls fed a control diet (CD). These effects were not accompanied by any change in rat body weight. All these data suggest that the dyslipemic rats fed a moderate amount of dietary fish oil constitute a useful animal model to study diet-regulated insulin action.     

瑞舒伐他汀对糖尿病大鼠早期动脉粥样硬化形成的影响

目的:观察他汀类调脂药物瑞舒伐他汀(Rosuvastatin)对2型糖尿病(type2diabetesmellitus,T2DM)大鼠早期动脉粥样硬化形成的影响,并探讨其可能的机制。方法:将45只雄性SD大鼠随机分为正常对照组(NC组)、2型糖尿病组(DM组)、2型糖尿病瑞舒伐他汀治疗组(DR组),每组15只。以喂高糖高脂饮食方法建立SD大鼠糖尿病模型,DM组、DR组给予高糖高脂饮食1个月后腹腔注射25mg/kg链脲佐菌素;NC组给予普通饮食,注射枸橼酸缓冲液作为对照。在此基础上,DR组给予瑞舒伐他汀5mg/(kg.d)灌胃,NC组、DM组给予生理盐水灌胃。16周后测定各组大鼠总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平与稳态血糖(BG)、稳态胰岛素(PGI)浓度,用免疫组化法检测主动脉血管壁白细胞分化抗原40(clusterofdifferentiation 40,CD40)及基质金属蛋白酶-2(MMP-2)、激活蛋白-1(activator protein-1,AP-1)的表达水平。结果:DM组、DR组TC、TG、LDL-C与BG水平较NC组均显著升高(F=33.71~426....     

Induction of differentiation of undifferentiated cells into pancreatic beta cells in vertebrates

The beta cells of the pancreatic islets, which maintain glucose homeostasis by secreting insulin, are important cells for sustaining life. In recent years, islet transplantation has been performed as a treatment for type I diabetes. Since there are not enough donors for patients awaiting transplantation, beta cells grown in vitro are expected to be utilized as a substitute for islets. To obtain the cells with properties of human beta cells, it is necessary to understand the process by which human pancreatic islets are formed, as well as their structural characteristics. By using undifferentiated cells, such as Xenopus laevis animal caps and mouse ES cells, pancreatic tissue has shown to be able to be induced in vitro. Various attempts have been made to obtain human beta cells from human ES/iPS cells. Versatile methods have been developed and improved efficiency has been achieved by the use of low molecular weight compounds, but the challenge remains to prevent tumor formation and achieve functional maturation. Inducing the differentiation of somatic stem cells into insulin-producing cells has also brought us closer to clinical application. There are still many challenges related to the practical use of beta cells derived from undifferentiated cells, such as the development of methods to substitute these cells for host beta cells, standardization of the treatment protocol, quality control, and confirmation of safety. Research on the methods of inducing undifferentiated cells to differentiate into beta cells has shown definite progress, suggesting that cell therapy for diabetes may become a preferred therapeutic option over islet transplantation.