Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High levels of CD36 expression are found in triglyceride storing and secreting cells such as differentiated adipocytes and mammary secretory epithelial cells and in some capillary endothelial cells. We have found high levels of CD36 in the capillary endothelium of murine adipose tissue and in cardiac and skeletal muscles. Muscle cells themselves were CD36 negative. No CD36 was found in brain endothelium. Cardiac and skeletal muscle tissues are highly oxidative and catabolize long-chain fatty acids as a source of energy while brain tissue does not use long-chain fatty acids for energy production. Since capillary endothelial cell CD36 expression appeared to correlate with parenchymal cell fatty acid utilization and since CD26 has been identified recently as a long-chain fatty acid-binding protein, we examined heart tissue CD36 expression in murine models of insulin-dependent (nonobese diabetic, NOD) and non-insulin-dependent diabetes mellitus (KKAY). Diabetic NOD and KKAY mice had serum triglyceride levels 2.6- and 4.2-fold higher, respectively, than normal mice and exhibited 7- and 3.5-fold higher levels of heart microsomal CD36, respectively, than control mice. Mice fed a 40% fat diet expressed heart tissue CD36 at a level 3.5-fold higher than those fed a 9% fat diet. These data suggest that endothelial cell CD36 expression is related to parenchymal cell lipid metabolism.
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PMID:Heart CD36 expression is increased in murine models of diabetes and in mice fed a high fat diet. 754 2

Much biochemical evidence has implicated rat adipocyte CD36 (FAT) in membrane binding and transport of long-chain fatty acids (FA). Expression of the mRNA favored tissues with active FA metabolism and was upregulated in vivo with diabetes and with high fat feeding. In culture, CD36 mRNA was a strong marker of preadipocyte differentiation and was modulated by the same factors effective on mRNAs coding for other proteins involved in FA metabolism. In preadipocytes, long-chain FA or 2-bromopalmitate but not short-chain FA strongly induced CD36 mRNA within 8 h to an optimum within 24 h. Removal of the FA resulted in a decay of CD36 mRNA with a half life of about 12 h. In differentiated adipocytes, levels of CD36 mRNA were downregulated by the 3': 5'-cyclic adenosine monophosphate, cAMP, analog, 8-(4-chlorophenylthio) adenosine, 8-CPT, at concentrations of 1-100 microM. The effect, observed within 6 h, was optimal after 18 h and independent of the action of 8-CPT to mobilize FA. Regulation of CD36 expression by factors effective on expression of other proteins implicated in FA metabolism is consistent with its role in membrane FA transport.
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PMID:Regulation of FAT/CD36 gene expression: further evidence in support of a role of the protein in fatty acid binding/transport. 925 Jun 3

Blood cells are in continuous contact with the vascular endothelium. Endothelial cell culture, intravital videomicroscopy allowed the investigation of blood cell-endothelium interactions in dynamic conditions. In the various diseases, diabetes mellitus, sickle cell anemia and malaria, erythrocytes have an increased adhesion to endothelial cells. The presence of advanced glycation end products (AGE) on erythrocytes of diabetics is responsible for their binding to the receptor RAGE present on the endothelium. The AGE-RAGE binding provokes an oxidant stress and induces the expression of the adhesion molecule. Furthermore, erythrocyte AGE induce an increase in vascular permeability. In sickle cell anemia, the increased adhesiveness and the sickling of red blood cells are responsible for thrombosis. Plasmodium falciparum infestation of erythrocytes induces knob formation at the cell surface and the P. falciparum protein binding to CD36, ICAM-1 and thrombospondin present on the endothelium, and facilitates the parasite dissemination.
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PMID:[Erythrocyte adhesion to the vascular endothelium]. 1066 97

Little is known about the mechanisms involved in the preferential channeling of different fuels to fat and how the target tissue participates in this process. Dietary fatty acids have been shown to act as signaling molecules that bind and activate a new class of nuclear receptors, the peroxisome proliferator-activated receptors (PPARs). PPAR-gamma is particularly interesting because it may have the potential to link particular fatty acids with a program of gene expression involved in lipid storage and metabolism. We investigated whether a nutrient-sensing pathway is activated by an increased availability of lipid fuels in nine normal weight male volunteers. Using reverse transcriptase-polymerase chain reaction analysis, the mRNA expression of fatty acid translocase (FAT)/CD36, PPAR-gamma2, leptin, uncoupling protein (UCP)-2 and UCP-3, and tumor necrosis factor (TNF)-alpha was investigated in gluteal subcutaneous fat biopsies before and after 5 h infusions of saline or Intralipid (Pharmacia and Upjohn, Milan, Italy) plus heparin, which does not modify insulinemia. Marked increases in FAT/CD36 (724+/-18%; P < 0.05), PPAR-gamma2 (200+/-8%; P < 0.05), leptin (110+/-13%; P < 0.05), UCP-2 (120+/-7%; P < 0.05), UCP-3 (80+/-5%; P < 0.05), and TNF-alpha mRNA (130+/-12%; P < 0.05) were observed in comparison with pretreatment levels, whereas there was no change after saline infusion. These data suggest that the in vivo gene expression of FAT/CD36, PPAR-gamma2, leptin, UCP-2, UCP-3, and TNF-alpha in subcutaneous adipose tissue is regulated by circulating lipids independent of insulin and that prolonged hyperlipidemia may therefore contribute to increased fat metabolism and storage as a result of the increased expression of these proteins.
Diabetes 2000 Mar
PMID:Induction of fatty acid translocase/CD36, peroxisome proliferator-activated receptor-gamma2, leptin, uncoupling proteins 2 and 3, and tumor necrosis factor-alpha gene expression in human subcutaneous fat by lipid infusion. 1086 51

We investigated the effects of advanced glycation end products (AGEs) on the expression of oxidized low-density lipoprotein (OxLDL) receptors in human monocyte-derived macrophages and THP-1 cells treated with PMA. Both RT-PCR procedure and Northern blot analysis revealed that AGEs induced not only the gene expression of two major OxLDL receptors, macrophage scavenger receptor (MSR) class A and CD36, but also MSR-B I and lectin-like oxidized low-density lipoprotein receptor 1. Also, as a result of gel shift assay, AGEs increased transcriptional activities of AP-1, NF-kappaB, and peroxisome proliferator-activated receptor gamma. These findings indicate that AGEs-induced enhancement of these transcriptional activities might be involved in increased levels of mRNA for some of OxLDL receptors in THP-1-cells treated with PMA. The upregulated surface expression of these receptors on macrophage membranes was closely associated with increased uptake of modified LDL, and culminated in enhanced foam cell transformation. Thus, AGEs may be involved in the cause of variable levels of foam cell formation via the increased numbers of OxLDL receptors in accelerated atherosclerotic lesions of individuals with diabetes.
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PMID:Advanced glycation end products-induced gene expression of scavenger receptors in cultured human monocyte-derived macrophages. 1103 32

CD36 has been associated with diverse normal and pathologic processes. These include scavenger receptor functions (uptake of apoptotic cells and modified lipid), lipid metabolism and fatty acid transport, adhesion, angiogenesis, modulation of inflammation, transforming growth factor-beta activation, atherosclerosis, diabetes and cardiomyopathy. Although CD36 was identified more than 25 years ago, it is only with the advent of recent genetic technology that in-vivo evidence has emerged for its physiologic and pathologic relevance. As these in-vivo studies are expanded, we will gain further insight into the mechanism(s) by which CD36 transmits a cellular signal, and this will allow the design of specific therapeutics that impact on a particular function of CD36.
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PMID:CD36 and atherosclerosis. 1104 91

Studies in the NOD mouse model suggest that development of diabetes mellitus type I can be prevented and established disease cured by deviation towards a Th2-type response. To obtain insight into whether this approach may be applicable to human disease, we investigated the Th1/Th2 cytokine balance in pancreatic tissue from two patients with diabetes of recent onset (Case 1, accidental death; Case 2, ketoacidosis). Using the polymerase chain reaction to amplify reverse-transcribed cDNA, signals for actin and CD36 confirmed mRNA integrity and the presence of T cells in pancreatic tissue from both patients and from a control. IFN-gamma cDNA was also amplified from all three tissues. However, IL-4 (but not IL-10) cDNA, was amplified from the pancreas of Case 1. Conversely, IL-10 (but not IL-4) cDNA was amplified from the the pancreas of Case 2. The control pancreas yielded specific signals for both IL-4 and IL-10. Our data extend the limited database on Th1 and Th2 cytokine expression in human pancreatic tissue from recently diagnosed diabetics. Moreover, together with previous observations, our findings raise the possibility that the lack of both IL-4 and IL-10 may be associated with the development of IDDM in humans.
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PMID:Presence of interleukin 4 or interleukin 10, but not both cytokines, in pancreatic tissue of two patients with recently diagnosed diabetes mellitus type I. 1109 95

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is highly expressed in lipid-accumulating macrophages of the coronary artery. In light of this, the wide-spread clinical use of thiazolidinediones (TZDs) in the treatment of type II diabetes raises concerns about the role of PPAR-gamma in macrophage function and disease progression. To define the role of PPAR-gamma in macrophage biology, we used homologous recombination to create embryonic stem cells that were homozygous for a null mutation in the PPAR-gamma gene. We demonstrate here that PPAR-gamma is neither essential for nor substantially affects the development of the macrophage lineage both in vitro and in vivo. In contrast, we show it is an important regulator of the scavenger receptor CD36, which has been genetically linked to lipid accumulation in macrophages. Both 15-deoxy-Delta12,14prostaglandin J2 and thiazolidinediones have anti-inflammatory effects that are independent of PPAR-gamma. We show that PPAR-gamma is required for positive effects of its ligands in modulating macrophage lipid metabolism, but that inhibitory effects on cytokine production and inflammation may be receptor independent.
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PMID:PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. 1113 7

Atherosclerotic coronary heart disease is a common complication of the insulin resistance syndrome that can occur with or without diabetes mellitus. Thiazolidinediones (TZDs), which are insulin-sensitizing antidiabetic agents, can modulate the development of atherosclerosis not only by changing the systemic metabolic conditions associated with insulin resistance but also by exerting direct effects on vascular wall cells that express peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear receptor for TZDs. Here we show that troglitazone, a TZD, significantly inhibited fatty streak lesion formation in apolipoprotein E-knockout mice fed a high-fat diet (en face aortic surface lesion areas were 6.9+/-2.5% vs 12.7+/-4.7%, P<0.05; cross-sectional lesion areas were 191 974+/-102 911 micrometer(2) vs 351 738+/-175 597 micrometer(2), P<0.05; n=10). Troglitazone attenuated hyperinsulinemic hyperglycemia and increased high density lipoprotein cholesterol levels. In the aorta, troglitazone markedly increased the mRNA levels of CD36, a scavenger receptor for oxidized low density lipoprotein, presumably by upregulating its expression, at least in part, in the macrophage foam cells. These results indicate that troglitazone potently inhibits fatty streak lesion formation by modulating both metabolic extracellular environments and arterial wall cell functions.
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PMID:Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL. 1123 16

The preferential channeling of different fuels to fat and changes in the transcription profile of adipose tissue and skeletal muscle are poorly understood processes involved in the pathogenesis of obesity and insulin resistance. Carbohydrate and lipid metabolism may play relevant roles in this context. Freely moving lean Zucker rats received 3- and 24-h infusions of Intralipid (Pharmacia and Upjohn, Milan, Italy) plus heparin, or saline plus heparin, to evaluate how an increase in free fatty acids (nonesterified fatty acid [NEFA]) modulates fat tissue and skeletal muscle gene expression and thus influences fuel partitioning. Glucose uptake was determined in various tissues at the end of the infusion period by means of the 2-deoxy-[1-3H]-D-glucose technique after a euglycemic-hyperinsulinemic clamp: high NEFA levels markedly decreased insulin-mediated glucose uptake in red fiber-type muscles but enhanced glucose utilization in visceral fat. Using reverse transcriptase-polymerase chain reaction and Northern blotting analyses, the mRNA expression of fatty acid translocase (FAT)/CD36, GLUT4, tumor necrosis factor (TNF)-alpha, peroxisome proliferator-activated receptor (PPAR)-gamma, leptin, uncoupling protein (UCP)-2, and UCP-3 was investigated in different fat depots and skeletal muscles before and after the study infusions. GLUT4 mRNA levels significantly decreased (by approximately 25%) in red fiber-type muscle (soleus) and increased (by approximately 45%) in visceral adipose tissue. Furthermore, there were marked increases in FAT/CD36, TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 mRNA levels in the visceral fat and muscle of the treated animals in comparison with those measured in the saline-treated animals. These data suggest that the in vivo gene expression of FAT/CD36, GLUT4, TNF-alpha, PPAR-gamma, leptin, UCP2, and UCP3 in visceral fat and red fiber-type muscle are differently regulated by circulating lipids and that selective insulin resistance seems to favor, at least in part, a prevention of fat accumulation in tissues not primarily destined for fat storage, thus contributing to increased adiposity and the development of a prediabetic syndrome.
Diabetes 2001 Mar
PMID:Preferential channeling of energy fuels toward fat rather than muscle during high free fatty acid availability in rats. 1124 80


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