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)

Noninsulin-dependent diabetes mellitus (NIDDM) is an increasingly common disease, which brings a number of life-threatening complications. In rats with experimentally induced diabetes, there is an increase in the capacity of the intestine to absorb monosaccharides. We have examined the activity and the expression of monosaccharide transporters in the intestine of patients suffering from NIDDM. Na(+)-dependent D-glucose transport was 3.3-fold higher in brush-border membrane (BBM) vesicles isolated from duodenal biopsies of NIDDM patients compared with healthy controls. Western analysis indicated that SGLT1 and GLUT5 protein levels were also 4.3- and 4.1-fold higher in diabetic patients. This was associated with threefold increases in SGLT1 and GLUT5 mRNA measured by Northern blotting. GLUT2 mRNA levels were also increased threefold in the intestine of diabetic patients. Analysis of other BBM proteins indicated that the activity and abundance of sucrase and lactase were increased by 1.5- to 2-fold and the level of the structural proteins villin and beta-actin was enhanced 2-fold in diabetic patients compared with controls. The increase in the capacity of the intestine to absorb monosaccharides in human NIDDM is due to a combination of intestinal structural change with a specific increase in the expression of the monosaccharide transporters SGLT1, GLUT5, and GLUT2.
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PMID:Expression of monosaccharide transporters in intestine of diabetic humans. 1180 45

This review explores the relation between evolution, ecology, and culture in determining human food preferences. The basic physiology and morphology of Homo sapiens sets boundaries to our eating habits, but within these boundaries human food preferences are remarkably varied, both within and between populations. This does not mean that variation is entirely cultural or learned, because genes and culture may coevolve to determine variation in dietary habits. This coevolution has been well elucidated in some cases, such as lactose tolerance (lactase persistence) in adults, but is less well understood in others, such as in favism in the Mediterranean and other regions. Genetic variation in bitter taste sensitivity has been well documented, and it affects food preferences (eg, avoidance of cruciferous vegetables). The selective advantage of this variation is not clear. In African populations, there is an association between insensitivity to bitter taste and the prevalence of malaria, which suggests that insensitivity may have been selected for in regions in which eating bitter plants would confer some protection against malaria. Another, more general, hypothesis is that variation in bitter taste sensitivity has coevolved with the use of spices in cooking, which, in turn, is thought to be a cultural tradition that reduces the dangers of microbial contamination of food. Our evolutionary heritage of food preferences and eating habits leaves us mismatched with the food environments we have created, which leads to problems such as obesity and type 2 diabetes.
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PMID:The gourmet ape: evolution and human food preferences. 1965 37

Consuming a balanced diet, such as the food groups represented on MyPlate, is key to improving health disparities. Despite the best of intentions, however, the dietary guidelines can be culturally challenging, particularly when it comes to dairy consumption. Many African and Hispanic Americans avoid milk and dairy products-key contributors of three shortfall nutrients (calcium, potassium and vitamin D)-because many people in these populations believe they are lactose intolerant. However, avoiding dairy can have significant health effects. An emerging body of evidence suggests that yogurt and other dairy products may help support reduced risk of heart disease, hypertension, obesity, and type 2 diabetes-conditions that disproportionately impact people of color. For this reason, the National Medical Association and the National Hispanic Medical Association issued a joint consensus statement recommending African Americans consume three to four servings of low-fat dairy every day. Cultured dairy products could play an important role in addressing these recommendations. Because of the presence of lactase-producing cultures, yogurt is often a more easily digestible alternative to milk, and thus more palatable to people who experience symptoms of lactose intolerance. This was a key factor cited in the final rule to include yogurt in the Special Supplemental Nutrition Program for Women, Infants, and Children.
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PMID:Nutrition and Health Disparities: The Role of Dairy in Improving Minority Health Outcomes. 2670 68

Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with diseases appropriately distributed among populations. Our results indicate that ET can filter association results to improve our ability to discover disease loci.
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PMID:Evolutionary triangulation: informing genetic association studies with evolutionary evidence. 2704 14

By the end of the 2010-s the prevalence of obesity among the indigenous people of the North approached to the all-Russia one and the speed of the spread of other metabolic disorders exceeded the average all-country levels. Aim of this review is to analyze data on the increase in consumption and variety of sugars coupled with a genetic specificity of regulation of saccharidase activity and their possible impact on the matters. Results. It have been shown that the traditional protein-lipid-based northern type diet has substantially changed and now contains a high proportion of carbohydrates. The carbohydrate per capita consumption among the indigenous people of the North has reached the all-Russia average level (40 kg per year) which exceeds the European average of 36.2 kg per year. The variety of food disaccharides has also considerably increased. The daily consumption of sucrose, at the beginning of the 20th century it was the only sugar contained in the store-bought foods, increased from 30 g in the 1930s to 63-65 g in the 1990s. In addition, the proportion of sucrose dropped to 60-70 per cent, while the contribution of other disaccharides (lactose, trehalose) reached 30-40 per cent. Daily starch consumption has also increased and got close to the national average (males 228.5 g, females 157.5 g per day). Such a diet in itself increases the risk of metabolic disorders and obesity. The high prevalence of the genotypes that determine reduced levels or inability to produce sucrase-isomaltase, lactase, trehalase, salivary and pancreatic amylases among northerners becomes a negative cofactor. The evolutionary driven and embodied in genotype reduced ability of the indigenous Arctic people to digest complex carbohydrates is in a conflict with the growing consumption of sugars and starchy foods in modern conditions. The northern people have a high proportion of carriers of the AG deletion in SI gene (3.5-14.3% against 0.05-0.2% among Europeans) which determines malabsorption of sucrose. The CC/LCT genotype (96.6% in northerners, 36-49% in Russians) presumes lactose intolerance and is associated with the risk of childhood obesity. The occurrence of A allele in the rs2276064 locus of TREH gene (trehalose intolerance; 31.3-58.9% in northerners, 1.9% in Europeans) increases the probability of the onset of type 2 diabetes mellitus. According to preliminary estimates, 28-52% of the northerners completely lost AMY gene that precludes or drastically reduces the ability to digest starch. A reduction in the number of copies of AMY gene (the average number of copies AMY2A - 4, in, in northerners it is 1.0-1.4) is associated with overweight and obesity. Conclusion. The analysis shows that, in the case of the modern indigenous northerners, nutritional and genetic risks of metabolic disorders accumulate.
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PMID:[Carbohydrate-related nutritional and genetic risks of obesity for indigenous northerners]. 3081 Nov 29

Positive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that additional genetic elements in the locus may have contributed to evolutionary adaptation to famine by promoting energy storage, but which now confer susceptibility to metabolic diseases. We show here that the miR-128-1 microRNA, located at the center of the positively selected locus, represents a crucial metabolic regulator in mammals. Antisense targeting and genetic ablation of miR-128-1 in mouse metabolic disease models result in increased energy expenditure and amelioration of high-fat-diet-induced obesity and markedly improved glucose tolerance. A thrifty phenotype connected to miR-128-1-dependent energy storage may link ancient adaptation to famine and modern metabolic maladaptation associated with nutritional overabundance.
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PMID:A MicroRNA Linking Human Positive Selection and Metabolic Disorders. 3305 56