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)

The 70 kDa heat shock protein family plays important cardiac protective roles against myocardial injuries. Reduced myocardial protection is a common feature of diabetic myocardium. This study was carried out to define the changes in the 70 kDa heat shock protein family in the myocardium in the of streptozotocin-diabetes rats, and to explore the mechanisms through which diabetes alters the abundance of Hsp70/Hsc70 in cardiac muscle. In the diabetic myocardium, the abundance of Hsc70 was significantly reduced. The abundance of Hsp70 was low in cardiac muscle and was not induced in the diabetic myocardium. Unlike Hsp60, Hsp70 and Hsc70 did not augment insulin-like growth factor-I receptor signaling in cardiac muscle cells. In cultured cardiomyocytes, insulin directly increased the abundance of Hsc70, whereas insulin could not modulate Hsp70. Treating diabetic rats with insulin restored myocardial Hsc70 level, but phlorizin treatment failed to restore myocardial Hsc70. These in vivo and in vitro studies showed that downregulation of Hsc70 in diabetic myocardium was secondary to insulin deficiency. Thus, insulin played a major role in maintaining adequate expression of Hsc70 in cardiac muscle.
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PMID:Downregulation of the constitutively expressed Hsc70 in diabetic myocardium is mediated by insulin deficiency. 1689 76

Central (visceral) obesity is more closely associated with insulin resistance, type 2 diabetes, and cardiovascular disease than peripheral (subcutaneous) obesity, however the underlying differences in morphology and pathophysiology between subcutaneous and visceral adipose are largely unknown. To evaluate the effects of diabetes and rosiglitazone (RSG) treatment, the expression of mitochondrial Hsp60, UCP-1 and F4/80 in inguinal subcutaneous (SC) fat, composed of white and brown adipose tissues, and epididymal (EP) fat, mainly white adipose tissue, were evaluated. In diabetic db/db mice, there was significant increased number of aggregated macrophage foci compared to db/+ mice, especially in EP fat. On the other hand, the expression of mitochondrial Hsp60 protein was suppressed in both SC and EP fat of db/db mice compared to db/+ mice, and the expression level of mitochondrial Hsp60 in db/+ mice was lower in EP fat compared with SC. In db/db mice, RSG suppressed the number of aggregated macrophage foci in EP fat, but not in SC fat. RSG ameliorated the mitochondrial Hsp60 expression and induced the expression of UCP-1 in both SC and EP fat. Taken together, these data suggest that differences exist in mitochondrial and macrophage content, and in the response to RSG between visceral and subcutaneous adipose tissue, and adipose type and distribution may be important for obesity-linked insulin resistance.
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PMID:Comparison of mitochondrial and macrophage content between subcutaneous and visceral fat in db/db mice. 1743 81

We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.
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PMID:Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression. 1759 Jan 77

The Whitehall Study is a prospective epidemiological study of cardiovascular risk factors in healthy members of the British Civil Service, which has identified psychological distress as a major risk factor for coronary heart disease. The levels of circulating Hsp60 in 860 participants from the Whitehall cohort and 761 individuals diagnosed with diabetes have been measured and related to psychological, biological, and genetic factors. In the Whitehall participants, concentrations of Hsp60 ranged from undetectable to mg/mL levels. Circulating Hsp60 correlated with total and low-density lipoprotein (LDL) cholesterol and was positively associated with a flattened slope of cortisol decline over the day. Levels of this stress protein also correlated with measures of psychological stress including psychological distress, job demand, and low emotional support. Mass spectrometric analysis of circulating immunoreactive Hsp60 reveal that it is predominantly the intact protein with no mitochondrial import peptide, suggesting that this circulating protein emanates from mitochondria. The Hsp60 is stable when added to plasma and the levels in the circulation of individuals are remarkably constant over a 4-year period, suggesting plasma levels are partly genetically controlled. Sequence analysis of the HSP60-HSP10 intergenic promoter region identified a common variant 3175 C>G where the G allele had a frequency of 0.30 and was associated with higher Hsp60 levels in 761 type 2 diabetic patients. The extended range of plasma Hsp60 concentrations in the general population is genuine and is likely to be related to genetic, biological, and psychosocial risk factors for coronary artery disease.
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PMID:Plasma heat shock protein 60 and cardiovascular disease risk: the role of psychosocial, genetic, and biological factors. 1822 57

The peptide P277 contains a target epitope for diabetogenic T cells and it has been used as an ideal target antigen to develop vaccines against type 1 diabetes. A major problem in developing P277 vaccine is its low immunogenicity. Recent applications involving multiple copies of self-peptide in linear alignment and conjugation with carrier proteins appear to increase the immune response. In this study, we designed a method based on isocaudamer technique to repeat tandemly the 24-residue sequence P277, then 6 tandemly repeated copies of the peptide P277 were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-6xP277 as an immunogen. We examined the effect of the tandem repeats of the peptide P277 in eliciting an immune response by comparing the immunogenicity of the three immunogens: P277, HSP65-P277 and HSP65-6xP277. Immunization of mice with the fusion protein HSP65-6xP277 elicited much higher levels of specific anti-P277 antibodies than with P277 and HSP65-P277, which should suggest that multiple tandem repeats of a certain epitope is an efficient method to overcome the low immunogenicity of self-peptide antigens and the immunogen HSP65-6xP277 might be further developed to a vaccine against type 1 diabetes.
Exp Clin Endocrinol Diabetes 2008 Oct
PMID:Enhanced immunogenicity of peptide P277 by heat shock protein HSP65 vector carrying tandem repeats of P277 to prevent type 1 diabetes in NOD mice. 1847 88

To improve the efficacy of peptide P277 in preventing autoimmune diabetes, heat shock protein 65 kD (HSP65) of Mycobacterium tuberculosis var. bovis was fused with linear polypeptide epitope of P277 and expressed as soluble protein in Escherichia coli. The fusion protein HSP65-P277 was purified by anion exchange column chromatography and then used to immunize prediabetic NOD mice with three ip inoculations in absence of adjuvants. Serum samples from the immunized mice were collected monthly and the concentration of blood glucose was measured. The study showed that administration of HSP65-P277 to NOD mice could prevent the development of diabetes more efficiently than the peptide P277 itself or HSP65. Fused to heat shock protein 65 of Mycobacterium tuberculosis could improve the efficacy of diabetes prevention of P277 in nonobese diabetic mice. The results suggest the fusion protein of HSP65-P277 would be useful for treating insulin-dependent diabetes mellitus.
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PMID:[Improved efficacy of P277 fused to heat shock protein 65 of Mycobacterium tuberculosis against diabetes in nonobese diabetic mice]. 1861 76

Adipocytes represent an important cellular source of inflammatory mediators. However, the signals for the induction of proinflammatory adipocyte activities are largely unknown. Here, we demonstrate that heat shock protein (Hsp) 60, a potent stimulator of innate immunity, induces the release of the inflammatory mediators interleukin-6, CXCL1 and monocyte chemoattractant protein-1 in a time- and concentration-dependent manner from cells of the adipocyte line 3T3-L1 and from adipocytes of obese mice. These results identify Hsp60 as an important regulator of adipocyte functions which contribute to the development of inflammatory processes as observed in diabetes and diabetes-associated complications.
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PMID:Heat shock protein 60 induces inflammatory mediators in mouse adipocytes. 1861 64

Largely due to better control of infectious diseases and significant advances in biomedical research, life expectancy worldwide has increased dramatically in the last three decades. However, as the average age of the population has risen, the incidence of chronic age-related diseases such as arthritis, Alzheimer's, Parkinson's, cardiovascular disease, cancer, osteoporosis, benign prostatic hyperplasia, and late-onset diabetes have increased and have become serious public health problem, as well. The etiology of these disorders is still incompletely understood, therefore, neither preventive strategies nor long-term effective treatment modalities are available for these disorders. In keeping with the aforementioned, the ultimate goal in cardiovascular research is to prevent the onset of cardiovascular episodes and thereby allow successful ageing without morbidity and cognitive decline. Herein, I argue that cardiovascular episodes could be contained with relatively simple approaches. Cardiovascular disorder is characterized by cellular and molecular changes that are commonplace in age-related diseases in other organ system, such alterations include increased level of oxidative stress, perturbed energy metabolism, and "horror autotoxicus" largely brought about by the perturbation of ubiquitin -proteasome system, and excessive oxidative stress damage to the cardiac muscle cells and tissues, and cross-reactions of specific antibodies against human heat shock protein 60 with that of mycobacterial heat shock protein 65. "Horror autotoxicus", a Latin expression, is a term coined by Paul Ehrlich at the turn of the last century to describe autoimmunity to self, or the attack of "self" by immune system, which ultimately results to autoimmune condition. Based on the currently available data, the risk of cardiovascular episodes and several other age-related disorders, including cancer, Alzheimer's disease and diabetes, is known to be influenced by the nature and level of food intake. Now, a wealth of scientific data from studies of rodents and monkeys has documented the significant beneficial effects of calorie restriction (CR) or dietary restriction (DR), and multiple antioxidant agents in extending life span and reducing the incidence of progeroid-related diseases. Reduced levels of cellular oxidative stress, protection of genome from deleterious damage, detoxification of toxic molecules, and enhancement of energy homeostasis, contribute to the beneficial effects of dietary restriction and multiple antioxidant agents. Recent findings suggest that employment of DR and multiple antioxidant agents (including, catalase, glutathione peroxidase, CuZn superoxide dismutase, and Mn superoxide dismutase = enzymes forming the primary defense against oxygen toxicity), and ozone therapy may mount an effective resistance to pathogenic factors relevant to the pathogenesis of cardiovascular episodes. Hence, while further studies will be needed to establish the extent to which CR and multiple antioxidant agents will reduce incidence of cardiovascular episodes in humans, it would seem prudent to recommend CR and multiple antioxidant agents as widely applicable preventive approach for cardiovascular disorders and other progeroid-related disorders.
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PMID:Cardiovascular disease could be contained based on currently available data! 1864 94

Heat shock protein 60 (HSPD1) plays a critical role in myocardial protection. Its reduced expression may lower myocardial protection against ischemic injury in the diabetic state. This study was conducted to investigate the natural course of fructose-fed insulin-resistant rats, define changes in myocardial HSPD1 expression, and determine the effects of thiazolidinedione or anti-hypertensive treatment. Results showed that insulin resistance with hyperinsulinemia and hypertension developed after 6 weeks of fructose feeding. This time-course study also showed that myocardial HSPD1 expression was mildly increased in week 6 (P=0.05) and significantly increased in week 8. Rosiglitazone-treated rats had restored systolic blood pressure (BP) and normalized plasma insulin level during oral glucose tolerance tests, whereas amlodipine-treated rats restored only systolic BP. Both amlodipine and rosiglitazone treatments normalized the abundance of myocardial HSPD1 expression in fructose-fed rats. When these rats received streptozotocin injection and diabetes developed, myocardial HSPD1 expression decreased despite persistent hypertension. In conclusion, this is the first study to report that myocardial HSPD1 expression is increased in high-fructose-fed rats, which may be due to increased BP. Once the high-fructose-fed rats developed diabetes with insulin deficiency, the myocardial HSPD1 expression decreased in spite of persistent hypertension.
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PMID:Myocardial heat shock protein 60 expression in insulin-resistant and diabetic rats. 1894 49

Heat-shock proteins are molecules with extensive data showing their potential as immunomodulators of different types of diseases. The gene of HSP65 from Mycobacterium leprae has shown prophylactic and immunotherapeutic effects against a broad arrays of experimental models including tuberculosis, leishmaniasis, arthritis and diabetes. With this in mind, we tested the DNAhsp65 vaccine using an experimental model of Paraccocidiodomycosis, an important endemic mycosis in Latin America. The intramuscular immunization with DNAhsp65 induced, in BALB/c mice, an increase of Th1-levels cytokines and a reduction of fungal burdens resulted in a marked reduction of collagen and lung remodeling. DNAhsp65 may be an attractive candidate for prevention, therapy and as an adjuvant for mycosis treatment.
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PMID:DNAhsp65 vaccination induces protection in mice against Paracoccidioides brasiliensis infection. 1902 37


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