Structure, function, and immunogenicity of human insulinoma cells.


:Dissociated human insulinoma cells were plated onto plastic multiwell dishes. Cells were maintained for 1 mo on plastic with three passages. Cultures consisted of small colonies with some areas of stratification and few intercellular spaces. Ultrastructural studies indicated that cultured cells had epithelial features with desmosomes at cell-to-cell contacts and intermediate filaments in addition to secretory granules in the cytoplasm. Insulin and C-peptide were released in equimolar amounts in culture media. When challenged for 30 min with 16.7 mM glucose, 1 mM 3-isobutyl-1-methylxanthine, 4 mM tolbutamide, or 10(-6) M glucagon, insulinoma cells responded by a 1.5-, 1.5-, 2-, or 3-fold increase, respectively, in insulin release above baseline levels. A 15-min challenge with 10(-5) M isoproterenol increased insulin secretion by 1.85-fold. By indirect immunofluorescence, an anti-insulin antibody reacted positively with cell cytoplasm, whereas anti-somatostatin and anti-glucagon antibodies did not. Insulinoma cell surface expressed class I MHC molecules but not class II molecules. Immediately after isolation, crude insulinoma cells were contaminated by 2% of DR+ cells from nonislet components that disappeared after several weeks in culture. The ability of insulinoma cells to stimulate allogenic T-lymphocyte proliferation was assessed by [3H]thymidine incorporation in mixed culture combinations. Crude insulinoma cells elicited a strong lymphoproliferative response with a stimulation index ranging between 3.5 and 7, whereas no stimulation was found after 1 mo in culture. It is postulated that absence of class II-positive cells in the stimulatory cell preparation conditioned this immune tolerance across the major histocompatibility barrier.(ABSTRACT TRUNCATED AT 250 WORDS)






Thivolet CH,Demidem A,Haftek M,Durand A,Bertrand J




Has Abstract


1988-09-01 00:00:00














  • Macrophage scavenger receptor-a-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation.

    abstract::Microinflammation is a common major mechanism in the pathogenesis of diabetic vascular complications, including diabetic nephropathy. Macrophage scavenger receptor-A (SR-A) is a multifunctional receptor expressed on macrophages. This study aimed to determine the role of SR-A in diabetic nephropathy using SR-A-deficien...


    pub_type: 杂志文章


    authors: Usui HK,Shikata K,Sasaki M,Okada S,Matsuda M,Shikata Y,Ogawa D,Kido Y,Nagase R,Yozai K,Ohga S,Tone A,Wada J,Takeya M,Horiuchi S,Kodama T,Makino H

    更新日期:2007-02-01 00:00:00

  • Biohybrid artificial pancreas. Long-term insulin secretion by devices seeded with canine islets.

    abstract::Long-term insulin secretion was investigated in seven biohybrid capillary devices seeded with canine islets. Approximately 50,000 islets could be isolated from a single canine pancreas using collagenase digestion in conjunction with the recently described Velcro technique. Devices were perfused with tissue culture med...


    pub_type: 杂志文章


    authors: Araki Y,Solomon BA,Basile RM,Chick WL

    更新日期:1985-09-01 00:00:00

  • Reduced levels of mRNA encoding endoskeletal and growth-associated proteins in sensory ganglia in experimental diabetes.

    abstract::This study investigated changes in levels of mRNAs encoding the three neurofilament (NF) proteins NF-L (low), NF-M (medium), and NF-H (high) and two growth-associated proteins, GAP-43 and T alpha 1 alpha-tubulin, in lumbar dorsal root ganglia of control and streptozocin-induced diabetic rats. After 8 weeks of diabetes...


    pub_type: 杂志文章


    authors: Mohiuddin L,Fernyhough P,Tomlinson DR

    更新日期:1995-01-01 00:00:00

  • Adiponectin multimeric complexes and the metabolic syndrome trait cluster.

    abstract::Adiponectin circulates in human plasma mainly as a 180-kDa low molecular weight (LMW) hexamer and a high molecular weight (HMW) multimer of approximately 360 kDa. We comprehensively examined the relationships between circulating levels of total adiponectin, adiponectin multimers, and the relative distribution (i.e., r...


    pub_type: 杂志文章


    authors: Lara-Castro C,Luo N,Wallace P,Klein RL,Garvey WT

    更新日期:2006-01-01 00:00:00

  • Prediction of metabolic syndrome by low serum testosterone levels in men: results from the study of health in Pomerania.

    abstract:OBJECTIVE:The aim of this analysis was to assess the prospective association of serum testosterone and dehydroepiandrosterone sulfate (DHEAS) levels with incident metabolic syndrome (MetS) in men. RESEARCH DESIGN AND METHODS:Data were obtained from the Study of Health in Pomerania (SHIP), a population-based prospectiv...


    pub_type: 杂志文章


    authors: Haring R,Völzke H,Felix SB,Schipf S,Dörr M,Rosskopf D,Nauck M,Schöfl C,Wallaschofski H

    更新日期:2009-09-01 00:00:00

  • Altered hepatic and muscle substrate utilization provoked by GLUT4 ablation.

    abstract::Studies were conducted to explore altered substrate utilization and metabolism in GLUT4 null mice. Liver fatty acid synthase mRNA and fatty acid synthesis rates were dramatically increased in GLUT4 null mice compared with control mice and were supported by increased rates of the pentose phosphate pathway oxidative pha...


    pub_type: 杂志文章


    authors: Ranalletta M,Jiang H,Li J,Tsao TS,Stenbit AE,Yokoyama M,Katz EB,Charron MJ

    更新日期:2005-04-01 00:00:00

  • A genome-wide scan for type 2 diabetes in African-American families reveals evidence for a locus on chromosome 6q.

    abstract::African Americans are at increased risk of type 2 diabetes and many diabetes complications. We have carried out a genome-wide scan for African American type 2 diabetes using 638 affected sibling pairs (ASPs) from 247 families ascertained through impaired renal function to identify type 2 diabetes loci in this high-ris...


    pub_type: 杂志文章


    authors: Sale MM,Freedman BI,Langefeld CD,Williams AH,Hicks PJ,Colicigno CJ,Beck SR,Brown WM,Rich SS,Bowden DW

    更新日期:2004-03-01 00:00:00

  • Critical roles for macrophages in islet angiogenesis and maintenance during pancreatic degeneration.

    abstract:OBJECTIVE:Chronic pancreatitis, characterized by pancreatic exocrine tissue destruction with initial maintenance of islets, eventually leads to insulin-dependent diabetes in most patients. Mice deficient for the transcription factors E2F1 and E2F2 suffer from a chronic pancreatitis-like syndrome and become diabetic. Su...


    pub_type: 杂志文章


    authors: Tessem JS,Jensen JN,Pelli H,Dai XM,Zong XH,Stanley ER,Jensen J,DeGregori J

    更新日期:2008-06-01 00:00:00

  • A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study Group.

    abstract::Coxsackievirus B infections have been associated with clinical manifestation of insulin-dependent diabetes mellitus (IDDM) in several studies, but their initiating role in the slowly progressing beta-cell damage is not known. This is the first prospective study designed to assess the role of coxsackie B and other ente...


    pub_type: 杂志文章


    authors: Hyöty H,Hiltunen M,Knip M,Laakkonen M,Vähäsalo P,Karjalainen J,Koskela P,Roivainen M,Leinikki P,Hovi T

    更新日期:1995-06-01 00:00:00

  • Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimal-model approach.

    abstract::Glucose tolerance depends on a complex interaction among insulin secretion from the beta-cells, clearance of the hormone, and the actions of insulin to accelerate glucose disappearance and inhibit endogenous glucose production. An additional factor, less well recognized, is the ability of glucose per se, independent o...


    pub_type: 杂志文章,评审


    authors: Bergman RN

    更新日期:1989-12-01 00:00:00

  • Absolute requirement of macrophages for the development and activation of beta-cell cytotoxic CD8+ T-cells in T-cell receptor transgenic NOD mice.

    abstract::The development of autoimmune diabetes in NOD mice results from selective destruction of beta-cells by a T-cell-dependent autoimmune process. However, the mechanisms that control the generation of beta-cell cytotoxic T-cells in vivo are poorly understood. We recently established 8.3-T-cell receptor (TCR)-beta transgen...


    pub_type: 杂志文章


    authors: Jun HS,Santamaria P,Lim HW,Zhang ML,Yoon JW

    更新日期:1999-01-01 00:00:00

  • Circulating immune complexes and platelet thromboxane synthesis in patients with insulin-dependent (type I) diabetes mellitus.

    abstract::Platelets from diabetic subjects with circulating immune complexes (CIC) synthesized greater amounts of thromboxane than did platelets from CIC-negative patients or controls. In view of the known action of CIC on platelet function, a relationship between these two factors may be suggested in the initiation and progres...


    pub_type: 杂志文章


    authors: Triolo G,Davi' G,Giardina E,Cardella F,Meli F,La Grutta A,Strano A,Bompiani GD

    更新日期:1984-08-01 00:00:00

  • The functional state of sympathetic nerves in spontaneously diabetic mice.

    abstract::I investigated biochemical parameters of sympathetic nerve function in spontaneously diabetic mice(C57 BL/KsJdb/db) and in their lean littermates. The concentration of norepinephrine (NE) in organs innervated by sympathetic nerves was significantly reduced in the heart, kidney, and salivary glands of mice (24 weeks ol...


    pub_type: 杂志文章


    authors: Giachetti A

    更新日期:1978-10-01 00:00:00

  • Diminished specific activity of cytosolic protein kinase C in sciatic nerve of streptozocin-induced diabetic rats and its correction by dietary myo-inositol.

    abstract::The impaired Na(+)-K(+)-ATPase activity in peripheral nerve from diabetic rats is prevented by dietary myo-inositol (MI) supplementation in vivo and corrected by protein kinase C (PKC) agonists in vitro, suggesting that PKC may mediate the effects of nerve MI depletion on Na(+)-K(+)-ATPase activity. However, little is...


    pub_type: 杂志文章


    authors: Kim J,Rushovich EH,Thomas TP,Ueda T,Agranoff BW,Greene DA

    更新日期:1991-11-01 00:00:00

  • The network of glucokinase-expressing cells in glucose homeostasis and the potential of glucokinase activators for diabetes therapy.

    abstract::The glucose-phosphorylating enzyme glucokinase has structural, kinetic, and molecular genetic features that are ideal for its primary role as glucose sensor in a network of neuro/endocrine sentinel cells that maintain glucose homeostasis in many vertebrates including humans. The glucokinase-containing, insulin-produci...


    pub_type: 杂志文章,评审


    authors: Matschinsky FM,Magnuson MA,Zelent D,Jetton TL,Doliba N,Han Y,Taub R,Grimsby J

    更新日期:2006-01-01 00:00:00

  • BB rat thymocytes cultured in the presence of islets lose their ability to transfer autoimmune diabetes.

    abstract::Thymocytes from adult BB rats can adoptively transfer autoimmune diabetes to athymic recipients. It is also known that the development of BB rat T-cells is recapitulated in adult thymus organ cultures (ATOCs). Based on these observations, we tested the hypothesis that cells capable of the adoptive transfer of diabetes...


    pub_type: 杂志文章


    authors: Whalen BJ,Marounek J,Weiser P,Appel MC,Greiner DL,Mordes JP,Rossini AA

    更新日期:2001-05-01 00:00:00

  • The newly inbred cohen diabetic rat: a nonobese normolipidemic genetic model of diet-induced type 2 diabetes expressing sex differences.

    abstract::The newly inbred Cohen diabetic rat is an exceptional experimental model of diet-induced type 2 diabetes mellitus that is the result of secondary inbreeding nearly 30 years after it originally had been established. Animals from the original colony were selectively inbred by stringent criteria for 10 additional generat...


    pub_type: 杂志文章


    authors: Weksler-Zangen S,Yagil C,Zangen DH,Ornoy A,Jacob HJ,Yagil Y

    更新日期:2001-11-01 00:00:00

  • Is cigarette smoking more frequent among insulin-treated diabetics?

    abstract::During epidemiologic investigations of vascular complications of diabetes in Warsaw the habit of cigarette smoking was analyzed in the subjects studied (4,530 diabetics). It was found that in the group of diabetics the number of ex-smokers was much greater (p less than 0.01) and that of present smokers lower (p less t...


    pub_type: 杂志文章


    authors: Czyzyk A,Królewski AS

    更新日期:1976-08-01 00:00:00

  • The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients.

    abstract::We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ult...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Economides PA,Khaodhiar L,Caselli A,Caballero AE,Keenan H,Bursell SE,King GL,Johnstone MT,Horton ES,Veves A

    更新日期:2005-01-01 00:00:00

  • Adiponectin resistance and proinflammatory changes in the visceral adipose tissue induced by fructose consumption via ketohexokinase-dependent pathway.

    abstract::An epidemic of obesity and type 2 diabetes is linked with the increase in consumption of fructose-containing sugars, such as sucrose and high-fructose corn syrup. In mammalian cells, fructose is metabolized predominantly via phosphorylation to fructose-1 phosphate by ketohexokinase (KHK) or by alternative pathways. He...


    pub_type: 杂志文章


    authors: Marek G,Pannu V,Shanmugham P,Pancione B,Mascia D,Crosson S,Ishimoto T,Sautin YY

    更新日期:2015-02-01 00:00:00

  • Kinetics of in vivo muscle insulin-mediated glucose uptake in human obesity.

    abstract::The kinetics of in vivo insulin-mediated glucose uptake in human obesity have not been previously studied. To examine this, we used the glucose-clamp technique to measure whole-body and leg muscle glucose uptake in seven lean and six obese men during hyperinsulinemia (approximately 2000 pM) at four glucose levels (app...


    pub_type: 杂志文章


    authors: Laakso M,Edelman SV,Olefsky JM,Brechtel G,Wallace P,Baron AD

    更新日期:1990-08-01 00:00:00

  • 3,4-Dideoxyglucosone-3-ene induces apoptosis in renal tubular epithelial cells.

    abstract::Diabetes complications are caused by hyperglycemia. Hyperglycemia results in increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) has been ...


    pub_type: 杂志文章


    authors: Justo P,Sanz AB,Egido J,Ortiz A

    更新日期:2005-08-01 00:00:00

  • Heritability of proliferative diabetic retinopathy.

    abstract:OBJECTIVE:Diabetic nephropathy clusters in families, suggesting that genetic factors play a role in its pathogenesis. We investigated whether similar clustering exists for proliferative retinopathy in families with two or more siblings with type 1 diabetes. RESEARCH DESIGN AND METHODS:The FinnDiane Study has character...


    pub_type: 杂志文章


    authors: Hietala K,Forsblom C,Summanen P,Groop PH,FinnDiane Study Group.

    更新日期:2008-08-01 00:00:00

  • Experimental hyperosmolar diabetic syndrome. Ketogenic response to medium-chain triglycerides.

    abstract::The clinical features of the experimental hyperosmolar diabetic (EHD) rat model resemble those seen in the human syndrome--extreme hyperglycemia without ketoacidosis is common to both. The absence of ketoacidosis in the syndrome has been ascribed to both substrate (free fatty acid) deficiency and to interference with ...


    pub_type: 杂志文章


    authors: Gordon EE,Duga J

    更新日期:1975-03-01 00:00:00

  • Reduction of Ptf1a gene dosage causes pancreatic hypoplasia and diabetes in mice.

    abstract:OBJECTIVE:Most pancreatic endocrine cells derive from Ptf1a-expressing progenitor cells. In humans, nonsense mutations in Ptf1a have recently been identified as a cause of permanent neonatal diabetes associated with pancreatic agenesis. The death of Ptf1a-null mice soon after birth has not allowed further insight into ...


    pub_type: 杂志文章


    authors: Fukuda A,Kawaguchi Y,Furuyama K,Kodama S,Horiguchi M,Kuhara T,Kawaguchi M,Terao M,Doi R,Wright CV,Hoshino M,Chiba T,Uemoto S

    更新日期:2008-09-01 00:00:00

  • Differences of pancreatic expression of 7B2 between C57BL/6J and C3H/HeJ mice and genetic polymorphisms at its locus (Sgne1).

    abstract::C57BL/6 (B6) mice develop glucose intolerance with age, whereas C3H/He (C3H) mice do not. In this study, we examined whether this differential glucose homeostasis was associated with differences of proteolytic activation of pancreatic prohormones. Radioimmunoassays showed comparable levels of fasting plasma insulin be...


    pub_type: 杂志文章


    authors: Schmidt G,Sirois F,Anini Y,Kauri LM,Gyamera-Acheampong C,Fleck E,Scott FW,Chrétien M,Mbikay M

    更新日期:2006-02-01 00:00:00

  • Interleukin-4 but not interleukin-10 protects against spontaneous and recurrent type 1 diabetes by activated CD1d-restricted invariant natural killer T-cells.

    abstract::In nonobese diabetic (NOD) mice, a deficiency in the number and function of invariant natural killer T-cells (iNKT cells) contributes to the onset of type 1 diabetes. The activation of CD1d-restricted iNKT cells by alpha-galactosylceramide (alpha-GalCer) corrects these deficiencies and protects against spontaneous and...


    pub_type: 杂志文章


    authors: Mi QS,Ly D,Zucker P,McGarry M,Delovitch TL

    更新日期:2004-05-01 00:00:00

  • Contribution of fatty acids released from lipolysis of plasma triglycerides to total plasma fatty acid flux and tissue-specific fatty acid uptake.

    abstract::There is controversy over the extent to which fatty acids (FAs) derived from plasma free FAs (FFAs) or from hydrolysis of plasma triglycerides (TGFAs) form communal or separate pools and what the contribution of each FA source is to cellular FA metabolism. Chylomicrons and lipid emulsions were labeled with [(3)H]triol...


    pub_type: 杂志文章


    authors: Teusink B,Voshol PJ,Dahlmans VE,Rensen PC,Pijl H,Romijn JA,Havekes LM

    更新日期:2003-03-01 00:00:00

  • Adverse effects of dietary glycotoxins on wound healing in genetically diabetic mice.

    abstract::Advanced glycoxidation end products (AGEs) are implicated in delayed diabetic wound healing. To test the role of diet-derived AGE on the rate of wound healing, we placed female db/db (+/+) (n = 55, 12 weeks old) and age-matched control db/db (+/-) mice (n = 45) on two diets that differed only in AGE content (high [H-A...


    pub_type: 杂志文章


    authors: Peppa M,Brem H,Ehrlich P,Zhang JG,Cai W,Li Z,Croitoru A,Thung S,Vlassara H

    更新日期:2003-11-01 00:00:00

  • Individual mice can be distinguished by the period of their islet calcium oscillations: is there an intrinsic islet period that is imprinted in vivo?

    abstract::Pulsatile insulin secretion in vivo is believed to be derived, in part, from the intrinsic glucose-dependent intracellular calcium concentration ([Ca2+]i) pulsatility of individual islets. In isolation, islets display fast, slow, or mixtures of fast and slow [Ca2+]i oscillations. We show that the period of islet [Ca2+...


    pub_type: 杂志文章


    authors: Nunemaker CS,Zhang M,Wasserman DH,McGuinness OP,Powers AC,Bertram R,Sherman A,Satin LS

    更新日期:2005-12-01 00:00:00