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

We evaluated the association of plasma insulin and other markers of insulin and glucose control with subsequent colorectal cancer. Incident colon (n = 132) and rectal (n = 41) cancer cases and matched controls (n = 346) were identified between baseline in 1989 and 2000 among participants in a community-based cohort in Washington County, Maryland. Circulating markers of insulin and glucose control were measured in baseline blood samples. Body mass index (BMI) and use of medications to treat diabetes mellitus were self-reported at baseline. Conditional logistic regression was used to estimate matched odds ratios (ORs). Compared with the lowest fourth, participants with insulin concentrations in the highest fourth were not at an increased risk of colorectal cancer [OR, 0.78; 95% confidence interval (CI), 0.45-1.35; P(trend) = 0.24]. Similarly, no associations were observed for the ratio of total cholesterol:HDL-cholesterol, triglycerides, and insulin-like growth factor binding protein 1. However, those in the highest fourth of glycosylated hemoglobin (HbA(1c)) level had a slightly increased risk of colorectal cancer (OR, 1.57; 95% CI, 0.94-2.60; P(trend) = 0.02). The OR of colorectal cancer was 1.70 (95% CI, 1.01-2.86; P(trend) = 0.08) comparing BMI >/=30 kg/m(2) to <25 kg/m(2). The OR of colorectal cancer was 2.43 (95% CI, 1.10-5.38) for the use of medications to treat diabetes. The associations of higher HbA(1c), higher BMI, and the use of medications to treat diabetes, with colorectal cancer lend support to the hypothesis that perturbations in insulin and glucose control may influence colorectal carcinogenesis. It is possible that HbA(1c), BMI, and the use of medications to treat diabetes, as a surrogate for protracted or severe type 2 diabetes mellitus, may have been better time-averaged indicators of hyperinsulinemia and hyperglycemia than the plasma markers that were measured once prediagnostically in a nonfasting population.
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PMID:Association of markers of insulin and glucose control with subsequent colorectal cancer risk. 1275 Feb 35

Peroxisome proliferator activated receptors (PPAR) belong to a family of nuclear receptors broadly distributed in the organism. Their pleiotropic role has been recently proved as well as their pathogenic significance in diabetes, obesity, cell cycle controlling, carcinogenesis, inflammation and atherosclerosis. The three types of PPAR identified until today have different tissue localization. PPARgamma, primarily identified in macrophages and adipocytes, play an important role in the expression of proteins essential for lipid metabolism and adipogenesis. PPARalpha are localized predominantly in hepatocytes and have also an important role in lipid metabolism. PPAR are though to be lipid sensors in organism. Carbohydrate metabolism is also under the control of PPAR and their exogenous ligands, (ie: thiasolidinediones), are important antidiabetic drugs.
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PMID:[Peroxisome proliferator activated receptors PPARs: their role in carbohydrate and lipid metabolism]. 1280 6

Peroxisome proliferation is a cellular response to many chemical compounds affects including natural and modified fatty acids, phthalate and adipate ester plasticizers, leukotriene antagonists, acetylsalicylic acid and certain pathophysiological conditions including dramatic change of cellular morphology and enzymatic activity. Peroxisome proliferation phenomenon is seen primarily in liver and kidney. Hormones and nutritional factor can regulate peroxisome proliferation response. Sustained peroxisome proliferation can lead to hepatocarcinogenesis. The three types of peroxisome proliferator activated receptor, termed PPAR alpha, PPAR beta, and PPAR gamma, expressed in specific tissue, are consisted of a specific a nuclear receptor superfamily. After more than 10 years world wide research, the function of PPAR is clarified, as PPAR gamma, the master of thrifty genes, controls the expression of genes relative to adipogenesis, diabetes mellitus and obesity. The receptor is involved in transcriptional control of numerous cellular processes including cell cycle control, inflammation, immunoregulation and carcinogenesis.
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PMID:[PPAR gamma--the master of thrifty genes]. 1290 43

The levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) peak in human in their twenties, then decrease gradually with age. The physiological importance of DHEA was not clear until recent research reports showing that DHEA has beneficial effects on preventing diabetes, malignancy, inflammation, osteoporosis, and collagen disease. We summarize our results concerning diabetes, hepatitis, and colon cancer. In 1982, Coleman et al. [Diabetes 31 (1982) 830] reported that DHEA decreased hyperglycemia in diabetic db/db mice, which become insulin resistant. We measured hepatic gluconeogenic enzymes in an attempt to elucidate the mechanical mechanism of DHEA action. The activity and gene expression of hepatic gluconeogenic enzyme such as glucose-6-phosphatase (G6Pase) was increased in db/db mice despite hyperinsulinemia compared to control db/+m mice. DHEA, like troglitazone, decreased these levels in db/db mice. We also showed that DHEA improved the insulin resistance caused by aging or obesity using the glucose clamp technique in another animal model. In humans, the serum DHEA concentration was shown to be associated with hyperinsulinemia in diabetes. It also became clear that DHEA increased insulin secretion in old-aged db/db mice. DHEA increases not only insulin sensitivity due to the effects in the liver and muscle, but also insulin secretion. As an effect of DHEA on T-cell mediated hepatitis induced by concanavalin A (ConA), DHEA reduced hepatic injury by inhibiting several inflammatory mediators and apoptosis. As an effect of DHEA on carcinogenesis, DHEA would be a potential chemopreventative agent against colon cancer because it decreases the number of azoxymethane (AOM) induced aberrant crypt foci, which is a possible precursor to adenoma and cancer in a murine model.Thus, since DHEA has many beneficial effects experimentally, we should consider administration of DHEA in the future, and common mechanisms among these actions of DHEA should be elucidated in further studies.
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PMID:Prevention of diabetes, hepatic injury, and colon cancer with dehydroepiandrosterone. 1294 37

The mitochondrion, long considered an organelle specific to energy metabolism, is in fact multi-functional and involved in many diseases. Mitochondrial DNA accumulates somatic mutations during aging, the progression of cancer and diabetes. Most cancer cells contain homoplasmic mutations in the mitochondrial genome. Although little is known about the contributions of mutations to carcinogenesis, some mutations in the nuclear genes encoding mitochondrial proteins have been identified as responsible for certain familial cancers. Mitochondria play an essential role in generating the germ line by releasing mitochondrial ribosomal RNAs, by which the germ line transfers the genetic information necessary for life to the next generation. Collaboration between mitochondria and the cytosol occurs in several metabolic pathways. Many enzymes involved in synthesizing uridine, heme and steroids and in the urea cycle are located inside mitochondria. Notably, a reaction involved in the synthesis of UMP is coupled with the energized state of mitochondria. Thus, the synthesis of DNA and RNA should be indirectly coupled with the energized state of mitochondria. Additionally, storing calcium is an important role of mitochondria. Calcium functions as a second messenger in signal transduction, however, it also activates several proteinases or lipases to induce damage. The mitochondrion plays a significant role in necrosis and is a center for apoptosis, determining its initiation, regulation and execution. Thus, the mitochondrion is widely involved in cell proliferation, cell death and disease.
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PMID:A multi-functional organelle mitochondrion is involved in cell death, proliferation and disease. 1452 64

Dietary restriction (DR) increases the life span and retards aging, in part, by limiting free radical generation and oxidative damage. DR also reduces body mass, a major determinant of bone mass across the life span. We tested the hypothesis that DR has its most beneficial effects on bone in mouse strains with high free radical generation (sensitive to carcinogenesis [SENCAR] > C57 > DBA) versus the hypothesis that bone mass at weight-bearing sites is determined by body mass in DR and ad libitum (AL)-fed mice. Male mice of each strain were killed at 10 weeks of age (t(0)) or randomized to an AL-fed or 30% DR feeding regimen for 6 months. Food consumption by AL-fed mice was measured daily, and DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. Body fat (%) and bone mineral density (BMD) and content (BMC) were determined by PIXImus densitometry. There were strain-dependent effects on body mass, crown-to-rump length, percent body fat, and total body, femoral, and vertebral BMD and BMC under all conditions. SENCAR mice were heavier, longer, had larger bones, and generally exhibited higher total body, femoral, and vertebral BMC and BMD than C57 and DBA mice. DR had beneficial effects on BMD and BMC in the vertebrae of the SENCAR mouse model of high free radical generation and in the obese, diabetes-prone C57 mouse model of high end-stage protein glycation. DR DBA and SENCAR mice had lower femoral BMDs and BMCs than their respective AL-fed controls. Regression analysis confirmed linear relationships between total and lean body mass and total body and femoral BMDs and BMCs, suggesting that physiologic adaptation to a lower body mass accounts for the lower femoral bone mineral values observed in DR versus AL-fed mice. Thus, both hypotheses are, at least, partially valid. DR is beneficial in the trabeculae-rich vertebrae of animal models of high oxidant stress, and total/lean body mass determines BMD and BMC in the weight-bearing femur in DR and AL-fed mice.
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PMID:Effects of dietary restriction on total body, femoral, and vertebral bone in SENCAR, C57BL/6, and DBA/2 mice. 1456 77

The genetic and histopathological backgrounds of adrenocortical tumorigenesis remain poorly characterized. In other tissues, there is conclusive evidence that hyperplasia and adenomas precede cancer. In the adrenal, there are few clinical cases of either hyperplasia or adenoma associated with later development of cancer, and there are few biological studies that attempt to characterize this process molecularly. Current research focuses on the early lesions of the adrenal cortex because of their possible molecular link with carcinogenesis, and evidence of their frequent association with atypical forms of Cushing's and Conn's syndromes, obesity, hypertension and/or diabetes. These studies indicate a model for oncogenesis that is the same as that in other tissues. The rarity of adrenal cancer compared to benign lesions could be a clue to unique features of adrenocortical cells. It might also highlight the function of genes that are associated with endocrine tumors in the context of which the concept of gene 'conductors' is introduced here.
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PMID:Genetics of adrenocortical tumors: gatekeepers, landscapers and conductors in symphony. 1458 Jul 59

Increased risks of cancers and oxidative DNA damage have been observed in diabetic patients. Many endogenous aldehydes such as 3-deoxyglucosone and glyceraldehyde (GA) increase under hyperglycemic conditions. We showed that these aldehydes induced Cu(II)-mediated DNA damage, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation. GA had the strongest ability to damage DNA, and addition of low concentrations of H2O2 markedly enhanced the DNA damage. GA significantly increased 8-oxodG formation in human cultured cells (HL-60), and H2O2 enhanced it. We conclude that oxidative DNA damage by hyperglycemia-related aldehydes, especially GA, and marked enhancement of DNA damage by H2O2 may participate in diabetes-associated carcinogenesis.
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PMID:Oxidative DNA damage by hyperglycemia-related aldehydes and its marked enhancement by hydrogen peroxide. 1459 28

Regenerating gene (Reg or REG) family, within the superfamily of C-type lectin, is mainly involved in the liver, pancreatic, gastric and intestinal cell proliferation or differentiation. Considerable attention has focused on Reg family and its structurally related molecules. Over the last 15 years, 17 members of the Reg family have been cloned and sequenced. They have been considered as members of a conserved protein family sharing structural and some functional properties being involved in injury, inflammation, diabetes and carcinogenesis. We previously identified Reg IV as a strong candidate for a gene that was highly expressed in colorectal adenoma when compared to normal mucosa based on suppression subtractive hybridization (SSH), reverse Northern blot, semi-quantitative reverse transcriptase PCR (RT-PCR) and Northern blot. In situ hybridization results further support that overexpression of Reg IV may be an early event in colorectal carcinogenesis. We suggest that detection of Reg IV overexpression might be useful in the early diagnosis of carcinomatous transformation of adenoma. This review summarizes the roles of Reg family in diseases in the literature as well as our recent results of Reg IV in colorectal cancer. The biological properties of Reg family and its possible roles in human diseases are discussed. We particularly focus on the roles of Reg family as sensitive reactants of tissue injury, prognostic indicators of tumor survival and early biomarkers of carcinogenesis. In addition to our current understanding of Reg gene functions, we postulate that there might be relationships between Reg family and microsatellite instability, apoptosis and cancer with a poor prognosis. Investigation of the correlation between tumor Reg expression and survival rate, and analysis of the Reg gene status in human malignancies, are required to elucidate the biologic consequences of Reg gene expression, the implications for Reg gene regulation of cell growth, tumorigenesis, and the progression of cancer. It needs to be further attested whether Reg gene family is applicable in early detection of cancer and whether Reg and Reg-related molecules can offer novel molecular targets for anticancer therapeutics. This has implications with regard to prognosis, such as in monitoring cancer initiation, progression and recurrence, as well as the design of chemotherapeutic drugs.
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PMID:Reg gene family and human diseases. 1466 3

Arsenic is a naturally occurring element, but anthropogenic activities can lead to a substantial contamination of the environment. Exposure to arsenic has been associated with a significant number of adverse health effects in humans including: cardiovascular disease, diabetes, hearing loss, developmental abnormalities, anemia, neurologic and neurobehavioral disorder, leukopenia, eosinophilia, fibrosis of the liver and the kidney and various neoplasms. However, the cellular and molecular events associated with arsenic toxicity are poorly understood. Also, the precise mechanisms by which arsenic acts as a carcinogen in humans remain to be elucidated. In the present study, we used human liver carcinoma (HepG2) cells as a model to study the molecular mechanisms of arsenic-induced toxicity and carcinogenesis. We hypothesized that arsenic-induced expression of stress genes and related proteins may play a role in the cellular and molecular events leading to toxicity and tumorigenesis in liver cells. To test this hypothesis, we performed the MTT-assay for cell viability, the CAT-Tox (L) assay for gene induction, and the Western Blot analysis to assess the expression of cellular proteins including c-fos, HMTIIA, HSP70 and p53. Data obtained from the MTT assay indicated a strong dose-response relationship with respect to arsenic trioxide toxicity. Upon 48 hr of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50) was computed to be 8.55 +/- 0.58 microg/ml. The CAT-Tox (L) assay showed statistically significant inductions (p<0.05) of c-fos, HMTIIA, and HSP70. Western blot analysis also demonstrated a dose-response relationship with regard to expression of specific cellular proteins. The p53 protein was expressed in arsenic trioxide-treated cells, however, the densitometric analysis did not show any significant differences (p<0.05) between treated and control cells. The lack of a significant induction of p53 may be due to the potential mitogenic effect of arsenic at low levels of arsenic exposure.
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PMID:Arsenic trioxide-induced transcriptional activation of stress genes and expression of related proteins in human liver carcinoma cells (HepG2). 1468 89


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