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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous data demonstrated that one rat insulinoma cell line, RINm5F cells, which is a rat beta-cell line derived from a pancreatic tumor, express mRNA coding for both the low- and the high-affinity nerve growth factor receptors. Goals of this study were to extend our data to other beta-cell lines and fetal islets in primary culture and to study further the binding characteristics of nerve growth factor receptors on beta-cells. Northern blot analysis revealed that not only a panel of endocrine beta-cell lines (RINm5F, INS-1, beta-TC3) but also fetal rat islets in primary culture express mRNA coding for trk-A, which has been proposed to be the neuronal high-affinity nerve growth factor receptors. Reverse polymerase chain reaction followed by sequencing revealed that the sequence of trk-A receptor in RINm5F cells is identical to that of trk-A expressed in PC12 cells. The expression of the low-affinity nerve growth factor receptor was examined by Northern blot analysis that showed low-affinity nerve growth factor receptor to be expressed in RINm5F and INS-1 cell lines, in fetal rat islets in primary culture, but not in beta-TC3-cells. Binding experiments revealed the presence of low- and high-affinity nerve growth factor binding sites, identical to those described for PC12 cells, on RINm5F and INS-1 cells and only high-affinity binding sites on beta-TC3 cells. Exposure of all three beta-cell lines to nerve growth factor increased NGFI-A and c-fos mRNA steady-state levels, showing that these receptors are functional.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Dec
PMID:Expression of functional nerve growth factor receptors in pancreatic beta-cell lines and fetal rat islets in primary culture. 824 29

Perinatal treatment of female mice with natural and synthetic estrogens including diethylstilbestrol (DES) results in estrogen-independent persistent proliferation and cornification of the vaginal epithelium. The dynamics of the induction of estrogen receptor (ER), c-jun, c-fos and c-myc mRNAs by 17 beta-estradiol (E2) was examined in the uterus and vagina of neonatally DES-exposed and -unexposed ovariectomized adult mice. In the uterus of neonatally DES-unexposed ovariectomized mice, the expression of ER mRNA increased within 1 h after E2 administration and declined by 12 h thereafter. ER mRNA in the vagina decreased within 1 h after the stimulation and recovered by 12 h thereafter. In the uterus, c-jun and c-fos mRNAs increased in concentration within 1 h after E2 administration, showing a peak 3 h after the stimulation; they decreased with time thereafter. In the vagina, the concentration of c-jun and c-fos mRNAs increased rapidly, reaching a peak within 1 h after the stimulation. However, the expression of c-myc in uterus and vagina was not changed by postpuberal E2. These results suggest that estrogen regulation of ER and proto-oncogene mRNAs in the vagina differs from those in the uterus. In the neonatally DES-exposed ovariectomized adult mice, uterine ER mRNA expression levels were significantly higher than in the unexposed ovariectomized controls; however, vaginal levels were drastically lower than in the controls. Expression of c-jun and c-fos mRNAs was greater in both the uterus (3- and 6-fold, respectively) and the vagina (18- and 4-fold) of neonatally DES-exposed mice than in controls. The ER mRNA and the increased levels of c-fos and c-jun mRNAs in both uterus and vagina of neonatally DES-exposed ovariectomized mice were not further altered by post-puberal E2 and may be related to ovary-independent persistent changes in the genital tract.
Exp Clin Endocrinol Diabetes 1996
PMID:Expression of estrogen receptor and proto-oncogene messenger ribonucleic acids in reproductive tracts of neonatally diethylstilbestrol-exposed female mice with or without post-puberal estrogen administration. 874 Sep 34

The ratio of membrane/cytosolic protein kinase C (PKC) activity and the levels of c-fos and c-jun expressions in uterine endometrial fibroblasts were increased and reached peak levels with the administration of estradiol, but were partially diminished by the addition of progesterone. The response of c-fos was earlier than that of c-jun. Twelve-0-tetradecanoylphorbol-13-acetate (TPA) increased c-fos and c-jun expressions in endometrial fibroblasts as estradiol did, and pretreatment with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) reduced the estrogen-inducible c-fos and c-jun expressions. Therefore, it is suggested that oncogenes c-fos and c-jun in uterine stromal cells might be induced by estrogen partly via PKC, involving the interplay of the anti-estrogenic effect of progesterone, and there might be a cross talk between estrogen and PKC stimulants for c-fos and c-jun expressions.
Exp Clin Endocrinol Diabetes 1995
PMID:Estrogen induces the expression of c-fos and c-jun genes in fibroblasts derived from human uterine endometrium. 878 11

Zucker fatty (fa/fa) rats exhibit overt obesity, hypercholesterolemia, hyperlipidemia, and hyperglycemia as recessive traits. The fa mutation has been determined to be a missense mutation in the extracellular domain of the leptin receptor. We report herein the construction of CHO cells that stably express the fa-type leptin receptor and the characterization of this receptor using mRNA expression levels of the immediate early genes, c-fos, c-jun, and jun-B, which are induced by leptin as a criterion of signal transduction. The fa-type receptor not only exhibits a slightly reduced leptin-binding affinity, but also performs reduced signal transduction.
Diabetes 1997 Jun
PMID:Leptin receptor of Zucker fatty rat performs reduced signal transduction. 916 83

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.
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PMID:Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy. 925 80

Cardiovascular diseases are the leading cause of morbidity and mortality in diabetes. Lipoprotein lipase (LPL), a major secretory product of macrophages, has been suggested to play a key role in the development of atherosclerosis. In the present study, we evaluated the effect of high glucose on macrophage LPL mRNA expression and secretion. Exposure of murine J774 macrophages to high D-glucose concentrations (20-30 mmol/l) resulted in a dramatic upregulation of LPL mRNA expression and immunoreactive mass. This effect was not observed when these cells were incubated in the presence of L-glucose or mannitol. High glucose concentrations were also found to enhance LPL gene expression and immunoreactive mass in human monocyte-derived macrophages. J774 cells cultured in a high glucose environment expressed increased c-fos mRNA levels. Treatment of these cells with c-fos antisense DNA or protein kinase C inhibitor inhibited the stimulatory effect of glucose on LPL mRNA expression. In J774 cells exposed to high glucose concentrations, enhanced nuclear protein binding to the AP-1-responsive region of the murine LPL promoter was observed, while LPL mRNA stability remained unchanged. Overall, these results demonstrate that high glucose upregulates macrophage LPL gene expression and immunoreactive mass and that this effect involves transcriptional events.
Diabetes 1998 Mar
PMID:Stimulatory effect of glucose on macrophage lipoprotein lipase expression and production. 951 50

Certain nutrients and growth factors can stimulate pancreatic beta-cell growth. However, the appropriate mitogenic signaling pathways in beta-cells have been relatively undefined. In this study, differential gene expression in NEDH rat insulinoma was compared with NEDH rat primary islet beta-cells. Differential mRNA display analysis revealed an elevated expression in insulinoma of VL30 transposons, S24 ribosomal protein, and cytochrome-C oxidaseVIIc that is typical for cells undergoing mitosis. A gene candidate approach revealed that mRNA levels of the oncogenes c-fos and c-jun were equivalently expressed in insulinoma and islet cells, as was the mRNA for the mitogenic signal transduction molecule insulin receptor substrate (IRS)-1. However, in contrast to that of IRS-1, IRS-2 gene expression was 60- to 70-fold higher in the insulinoma tissue compared with islets, which was reflected at the protein as well as the mRNA level. The specific elevated IRS-2 expression was a consistent observation across all rodent pancreatic beta-cell lines. To investigate whether IRS-2 was functional, serum-stimulated beta-cell proliferation was examined in isolated insulinoma cells. After a 48-h period of serum withdrawal, 24 h of serum refeeding rendered an 8- to 10-fold increase in [3H]thymidine incorporation into insulinoma cells. This serum-stimulated DNA synthesis was prevented by inhibitors of tyrosine protein kinase and phosphatidylinositol (PI) 3-kinase activities, as well as the activation of mitogen-activated protein (MAP) kinase and p70S6K. Examination of IRS-mediated signal transduction pathways indicated that after 10-15 min of serum refeeding, there was increased tyrosine phosphorylation of IRS-2 and pp60, and PI 3-kinase recruitment to IRS-2. Serum also increased the association of growth factor-bound protein 2/murine sons of sevenless 1 protein to a PI 3-kinase/IRS-2 protein complex. Moreover, serum also activated MAP-kinase (erk-1 and erk-2 isoforms) and 70 kD S6 kinase. Thus IRS-mediated signal transduction pathways are functional in pancreatic beta-cells. It is conceivable that IRS-2 expression in beta-cells contributes to maintaining the islet beta-cell population, complementary to observations in the IRS-2 knockout mouse in which beta-cell mass is markedly reduced.
Diabetes 1998 Jul
PMID:A specific increased expression of insulin receptor substrate 2 in pancreatic beta-cell lines is involved in mediating serum-stimulated beta-cell growth. 964 31

Diabetes induced by streptozotocin (STZ) in laboratory rats leads to impaired glucose metabolism in the heart and changes in myocardial contractile protein isoform expression and cardiac function. The purpose of this study was to investigate in vivo insulin signaling responses in the myocardium of STZ-diabetic rats. Insulin rapidly stimulated tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1) and, to a lesser extent, IRS-2 in normal and diabetic myocardium. In diabetic rats, there was 2-fold higher insulin receptor content and insulin-stimulated receptor tyrosine phosphorylation in comparison with control rats. IRS-1 tyrosine phosphorylation also increased in STZ diabetes in spite of a decrease in IRS-1 content, resulting in a 4-fold higher ratio of phosphorylated to total IRS-1. This was associated with 2-fold higher IRS-1 precipitable phosphatidylinositide 3-kinase activity in diabetic animals. Insulin stimulation of glycogen synthase activity was significantly diminished in STZ diabetes, consistent with resistance to insulin in a step downstream from phosphatidylinositide 3-kinase activation. Under the same experimental conditions, there was a marked increase in insulin stimulation of myocardial c-fos messenger RNA content in diabetic animals in comparison with controls. These data demonstrate altered early steps in insulin signaling in STZ-diabetic rat myocardium. Consequent oppositely directed disturbances in growth regulatory and glucose regulatory responses to insulin may contribute to the development of myocardial functional abnormalities in this model of diabetes.
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PMID:In vivo insulin signaling in the myocardium of streptozotocin-diabetic rats: opposite effects of diabetes on insulin stimulation of glycogen synthase and c-Fos. 1006 37

To better understand the link between fatty acid signaling and the pleiotropic effects of fatty acids in the pancreatic beta-cell, we investigated whether fatty acids regulate immediate-early response genes (IEGs) coding for transcription factors implicated in cell proliferation, differentiation, and apoptosis. Palmitate and oleate, but not long-chain polyunsaturated fatty acids, caused a pronounced accumulation of c-fos and nur-77 mRNAs in beta-cells (INS cells) to an extent similar to that produced by the protein kinase C (PKC) activator phorbol myristate acetate (PMA). The effect was dose dependent and occurred at concentrations between 0.1 and 0.5 mmol/l in the presence of 0.5% albumin. The action of the fatty acid occurred at the transcriptional level, and the mRNA accumulation displayed a bell-shaped kinetics with a maximal effect at 1 h. 2-Bromopalmitate was ineffective, indicating that fatty acids must be metabolized to cause their effect. Neither fatty acid was able to induce c-fos and nur-77 in PKC-downregulated cells or cells incubated in the presence of the Ca2+ channel blocker nifedipine or the Ca2+ chelator EGTA, suggesting involvement of the PKC and Ca2+ signaling pathways. Palmitate and oleate also increased c-fos protein expression and DNA binding activity of the transcription factor AP-1. Oleate, but not palmitate, increased [3H]thymidine incorporation in INS cells. Finally, both palmitate and oleate caused c-fos and nur-77 mRNA accumulation in isolated rat islets. It is suggested that IEG induction by the most abundant circulating fatty acids plays a role in the adaptive process of the beta-cell to hyperlipidemia. These results have implications for our understanding of obesity-associated diabetes and the link between fatty acids and tumorigenesis.
Diabetes 1999 Oct
PMID:Palmitate and oleate induce the immediate-early response genes c-fos and nur-77 in the pancreatic beta-cell line INS-1. 1051 66

Elevated levels of glycocojugates, commonly observed in the myocardium of diabetic animals and patients, are postulated to contribute to the myocardial dysfunction in diabetes. Previously, we reported that UDP-GlcNAc: Galbeta1-3GalNAcalphaRbeta1-6-N-acetylglucosaminyltransferas e (core 2 GlcNAc-T), a developmentally regulated enzyme of O-linked glycans biosynthesis pathway, is specifically increased in the heart of diabetic animals and is regulated by hyperglycemia and insulin. In this study, transgenic mice overexpressing core 2 GlcNAc-T with severe increase in cardiac core 2 GlcNAc-T activities were normal at birth but showed progressive and significant cardiac hypertrophy at 6 months of age. The heart of transgenic mice showed elevation of sialylated O-glycan and increases of c-fos gene expression and AP-1 activity, which are characteristics of cardiac stress. Furthermore, transfection of PC12 cells with core 2 GlcNAc-T also induced c-fos promoter activation, mitogen activated-protein kinase (MAPK) phosphorylation, Trk receptor glycosylation, and cell differentiation. These results suggested a novel role for core 2 GlcNAc-T in the development of diabetic cardiomyopathy and modulation of the MAP kinase pathway in the heart.-Koya, D., Dennis, J. W., Warren, C. E., Takahara, N., Schoen, F. J., Nishio, Y., Nakajima, T., Lipes, M. A., King, G. L. Overexpression of core 2 N-acetylglycosaminyltransferase enhances cytokine actions and induces hypertrophic myocardium in transgenic mice.
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PMID:Overexpression of core 2 N-acetylglycosaminyltransferase enhances cytokine actions and induces hypertrophic myocardium in transgenic mice. 1059 80


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