Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 1 diabetes results from autoimmune destruction of the pancreatic beta-cells. Although viruses have been implicated as etiologic factors, specific pathogenic mechanisms have not been identified. Recently, increased attention has focused on the role of the innate antiviral defense system in directing adaptive immune responses. In this context, the pathogenesis of type 1 diabetes may involve an aberrant response to endogenous or exogenous viruses or their products. The family of 2',5' oligoadenylate synthetases (2', 5' AS) are IFN-alpha-inducible, RNA-dependent effector molecules in the antiviral defense system. We show that lymphocytic 2',5' AS activity is significantly increased in type 1 diabetes, both in recent-onset and in long-standing type 1 diabetes, and in diabetic twins from monozygotic twin pairs. The activity of 2',5' AS was not elevated in patients with type 2 diabetes or multiple sclerosis thus excluding hyperglycemia or autoimmunity per se as inducing upregulation of enzyme activity. In recent-onset diabetic patients, lymphocyte levels of protein kinase p68 and MxA, two other IFN-alpha-inducible antiviral proteins, were similar to control levels. These data suggest that the increased 2',5' AS activity may reflect an aberrant response to viruses or RNA molecules originating from exogenous or endogenous sources.
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PMID:The antiviral 2',5'-oligoadenylate synthetase is persistently activated in type 1 diabetes. 1087 23

Genome-wide linkage scans using affected sibpair families are being conducted on many complex diseases, such as type 1 and type 2 diabetes, multiple sclerosis, rheumatoid arthritis, schizophrenia, asthma, cardiovascular diseases, obesity, and alcoholism. Despite extensive efforts by many groups, progress has been exceedingly slow, and only a few genes and some genomic regions involved in complex diseases have been identified. The general picture is one of difficulty in locating disease genes and replication of reported linkages. This results from the fact that complex diseases and traits may result principally from genetic variation that is relatively common in the general population involving a large number of genes, environmental factors, and their interactions. Genome-wide association studies are now feasible through the use of PCR methodologies with pooled DNA samples and microsatellite variation, and more recently single-nucleotide polymorphism (SNP) variation. Issues relating to significance levels in genome-wide linkage and association scans are discussed, and suggestions for dealing with false positive (type I) errors proposed.
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PMID:Significance levels in genome scans. 1103 36

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor transcription factor that regulates adipocyte differentiation and glucose homeostasis. PPARgamma agonists are potent therapeutic agents for the treatment of type 2 diabetes and obesity. PPARgamma agonists also prevent inflammation in animal models, suggesting their use for the treatment of human inflammatory diseases. Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated inflammatory demyelinating disease model of multiple sclerosis (MS) and IL-12 plays a crucial role in the pathogenesis of EAE and MS. In this study we have examined the effect of PPARgamma agonists on the pathogenesis of EAE. In vivo treatment of SJL/J mice with PPARgamma agonists, 15-deoxydelta(12,14) prostaglandin J2 or Ciglitazone, decreased the duration and clinical severity of active immunization and adoptive transfer models of EAE. PPARgamma agonists inhibited EAE in association with a decrease in IL-12 production and differentiation of neural antigen-specific Th1 cells. In vitro treatment of activated T cells with PPARgamma agonists inhibited IL-12-induced activation of JAK-STAT signaling pathway and Th1 differentiation. These findings highlight the fact that PPARgamma agonists regulate central nervous system inflammation and demyelination by inhibiting IL-12 production, IL-12 signaling and Th1 differentiation in EAE.
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PMID:Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation. 1196 Mar 3

Activation of peroxisome proliferator-activated receptors (PPARs) mediates the insulin-sensitizing effects of thiazolidinediones used for treatment of type 2 diabetes, owing to changes in the transcription and expression of genes influencing carbohydrate and lipid metabolism. However, PPAR activation can have additional effects upon cellular physiology, including anti-proliferative and anti-inflammatory. These effects are observed in many cell types, including brain glial cells and blood lymphocytes, cells whose activation contributes to the initiation and progression of damage occurring in neurological diseases such as Alzheimer's disease (AD) and multiple sclerosis (MS). In view of the need for development of additional therapeutic options, several recent studies have tested the possibility that PPAR agonists would be neuroprotective in these diseases. This paper will summarize data from cell culture experiments and from studies in animal models, demonstrating that PPARgamma agonists can exert neuroprotective effects, thereby providing the basis for the design of clinical trials to test the safety and efficacy of thiazolidinediones in neuroinflammatory conditions such as AD and MS.
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PMID:Therapeutic potential of peroxisome proliferator-activated receptor agonists for neurological disease. 1272 9

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor transcription factor that regulates cell growth, differentiation, and homeostasis. PPARgamma agonists are potent therapeutic agents for type 2 diabetes, obesity, and inflammation. Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated inflammatory demyelinating autoimmune disease model of multiple sclerosis. We have shown recently that PPARgamma agonists inhibit EAE by blocking IL-12 production, IL-12 signaling, and neural Ag-induced Th1 differentiation. In this study, we show that the PPARgamma-deficient heterozygous mice develop an exacerbated EAE with prolonged clinical symptoms than the wild-type littermates, following immunization with myelin oligodendrocyte glycoprotein (MOG) p35-55 peptide. The exacerbation of EAE in PPARgamma(+/-) mice associates with an increased expansion of CD4(+) and CD8(+) T cells and expression of CD40 and MHC class II molecules in response to MOGp35-55 Ag. The PPARgamma(+/-) mice also showed an increase in T cell proliferation and Th1 response to MOGp35-55 Ag than the wild-type littermates. These findings suggest that PPARgamma be a critical physiological regulator of CNS inflammation and demyelination in EAE and perhaps multiple sclerosis and other Th1 cell-mediated autoimmune diseases.
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PMID:Peroxisome proliferator-activated receptor-gamma-deficient heterozygous mice develop an exacerbated neural antigen-induced Th1 response and experimental allergic encephalomyelitis. 1463 82

As health care reform strategists increasingly recognize the critically important potential of effective everyday self-care decision making for reducing the burden of illness and the strain on health service systems, we must find ways to understand and support it. In this study, the authors investigate persons with expertise in self-care management of type 2 diabetes, HIV/AIDS, and multiple sclerosis to understand how everyday self-care decision making is learned and experienced. They used interview, think-aloud, and focus groups to construct an account of how persons affected by these chronic diseases make decisions in relation to the choices in their everyday lives and learn to manage the untoward effects of these conditions according to their unique contexts and values. The findings form a conceptual foundation for ongoing inquiry into this complex phenomenon and provide insights that might assist clinicians to understand more fully the responses and attitudes of those they serve.
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PMID:The structure of everyday self-care decision making in chronic illness. 1525 22

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are a class of nuclear transcription factors that are activated by fatty acids and their derivatives. One of these, PPARgamma, regulates responsiveness to insulin in adipose cells, and PPARgamma-activating drugs such as pioglitazone are used in the treatment of type 2 diabetes. PPARgamma acts in myeloid-lineage cells, including T-cells and macrophages, to suppress their activation and their elaboration of inflammatory molecules. PPARgamma activation also suppresses the activated phenotype in microglia, suggesting that PPARgamma-activating drugs may be of benefit in chronic neuroinflammatory diseases. Some, but not all, nonsteroidal anti-inflammatory agents (indomethacin and ibuprofen in particular) also have activating effects on PPARgamma. DISCUSSION AND CONCLUSIONS: These observations suggest on the one hand a role for PPARgamma-activating drugs in the treatment of chronic neuroinflammatory diseases-as shown for a patient with secondary progressive multiple sclerosis by Pershadsingh et al. in this issue of the Journal of Neuroinflammation-and suggest on the other hand a possible explanation for confusing and contradictory results in trials of nonsteroidal anti-inflammatory agents in Alzheimer's disease.
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PMID:PPARgamma, neuroinflammation, and disease. 1528 97

BACKGROUND: Ligands of the peroxisome proliferator-activated receptor-gamma (PPARgamma) induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. Preclinical studies have shown that the thiazolidinedione pioglitazone, an FDA-approved PPARgamma agonist used to treat type 2 diabetes, delays the onset and reduces the severity of clinical symptoms in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). We therefore tested the safety and therapeutic potential of oral pioglitazone in a patient with secondary MS. CASE PRESENTATION: The rationale and risks of taking pioglitazone were carefully explained to the patient, consent was obtained, and treatment was initiated at 15 mg per day p.o. and then increased by 15 mg biweekly to 45 mg per day p.o. for the duration of the treatment. Safety was assessed by measurements of metabolic profiles, blood pressure, and edema; effects on clinical symptoms were assessed by measurement of cognition, motor function and strength, and MRI. Within 4 weeks the patient exhibited increased appetite, cognition and attention span. After 12 months treatment, body weight increased from 27.3 to 35.9 kg (32%) and maintained throughout the duration of the study. Upper extremity strength and coordination improved, and increased fine coordination was noted unilaterally after 8 months and bilaterally after 15 months. After 8 months therapy, the patient demonstrated improvement in orientation, short-term memory, and attention span. MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events. CONCLUSIONS: In a patient with secondary progressive MS, daily treatment with 45 mg p.o. pioglitazone for 3 years induced apparent clinical improvement without adverse events. Pioglitazone should therefore be considered for further testing of therapeutic potential in MS patients.
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PMID:Effect of pioglitazone treatment in a patient with secondary multiple sclerosis. 1528 99

Patient-professional communication is a critically important element of effective chronic illness care. However, the dynamics of health care communication in supporting self-care management and effective coping with various chronic diseases is not well understood. The present study examined health care communication from the perspective of 38 patients with four distinct chronic conditions: end-stage renal disease (ESRD), non-insulin dependent diabetes mellitus (NIDDM), multiple sclerosis (MS), and fibromyalgia (FM). Analysis revealed the dimensions of courtesy, respect, and engagement to be inherent in communication priorities across conditions. However, distinct "disease worlds" among and between these chronic conditions illuminated salient differences within these dimensions, thereby illustrating the way in which relevant variables such as legitimacy, the availability of conventional treatments, and lifestyle implications shape the meaning of health care communication. The findings enlarge upon patient-centered approaches to health care communication and inform further analysis of the interactional dynamics associated with chronic conditions.
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PMID:The context of health care communication in chronic illness. 1532 81

Restricting caloric intake to 60-70% of normal adult weight maintenance requirement prolongs lifespan 30-50% and confers near perfect health across a broad range of species. Every other day feeding produces similar effects in rodents, and profound beneficial physiologic changes have been demonstrated in the absence of weight loss in ob/ob mice. Since May 2003 we have experimented with alternate day calorie restriction, one day consuming 20-50% of estimated daily caloric requirement and the next day ad lib eating, and have observed health benefits starting in as little as two weeks, in insulin resistance, asthma, seasonal allergies, infectious diseases of viral, bacterial and fungal origin (viral URI, recurrent bacterial tonsillitis, chronic sinusitis, periodontal disease), autoimmune disorder (rheumatoid arthritis), osteoarthritis, symptoms due to CNS inflammatory lesions (Tourette's, Meniere's) cardiac arrhythmias (PVCs, atrial fibrillation), menopause related hot flashes. We hypothesize that other many conditions would be delayed, prevented or improved, including Alzheimer's, Parkinson's, multiple sclerosis, brain injury due to thrombotic stroke atherosclerosis, NIDDM, congestive heart failure. Our hypothesis is supported by an article from 1957 in the Spanish medical literature which due to a translation error has been construed by several authors to be the only existing example of calorie restriction with good nutrition. We contend for reasons cited that there was no reduction in calories overall, but that the subjects were eating, on alternate days, either 900 calories or 2300 calories, averaging 1600, and that body weight was maintained. Thus they consumed either 56% or 144% of daily caloric requirement. The subjects were in a residence for old people, and all were in perfect health and over 65. Over three years, there were 6 deaths among 60 study subjects and 13 deaths among 60 ad lib-fed controls, non-significant difference. Study subjects were in hospital 123 days, controls 219, highly significant difference. We believe widespread use of this pattern of eating could impact influenza epidemics and other communicable diseases by improving resistance to infection. In addition to the health effects, this pattern of eating has proven to be a good method of weight control, and we are continuing to study the process in conjunction with the NIH.
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PMID:The effect on health of alternate day calorie restriction: eating less and more than needed on alternate days prolongs life. 1652 78


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