Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

To assess the quality of life (QOL) in elderly diabetic patients, 452 elderly outpatients aged over 60 years old who lived in 4 districts near our hospital were visited at home and of them were asked to follow 83 questionnaires concerning QOL by professional interviewers. Using the 37 questions about the impact of diabetes on elderly diabetic patients, we have developed the Elderly Diabetes Impact Scales (EDIS). The EDIS consisted of 6 subscales (burden of symptoms, burden of daily life, burden of diet therapy, burden of drug therapy, satisfaction, worry). Responses to questions were estimated with a 4-point multiple-choice assessment. The impact was rated from 1 (no impact, never worried, or very satisfied) to 4 (very burdened, always worried, or very dissatisfied) for each question and total EDIS scores were calculated by summing up the scores of the 37 questions. The internal consistency of the EDIS and its six subscales were of a satisfactory magnitude (0.66-0.88). There was also a significant correlation between the EDIS and PGC morale scales (r = -0.48, p < 0.001) and between the EDIS subscales and 3 moral components suggesting a convergent validity of the EDIS. The EDIS may be useful in evaluating the quality of life in elderly patients with diabetes mellitus.
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PMID:[Development of Elderly Diabetes Impact Scales (EDIS) in elderly patients with diabetes mellitus]. 886 39

As a part of a QOL study in elderly diabetes mellitus, we performed an interview conducted by professional interviewers on the sense of burden of dietary therapy in 383 elderly outpatients with diabetes mellitus aged over 60 years old. We used a scale on Burden of Dietary Therapy (BDT) that consisted of 7 questions (calorie restriction, dietary balance, regular dietary habits, restriction of favorite food, restriction of amounts of snacks, restrictions when eating out, burden of total dietary therapy). The sense of burden was rated from 1 (never burdened) to 4 (heavily burdened) for each question and the alpha coefficiency of the BDT scale was 0.80. Women, relatively younger elderly patients, hyperglycemic patients, or tablet-treated patients had higher BDT scale scores. The lower the positive family support scores and the higher the negative social support scores the greater was the BDT score. High BDT scores were significantly associated with low PGC moral scales (p < 0.001). The results suggest that the burden of dietary therapy could lower the quality of life in elderly patients with diabetes mellitus.
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PMID:[Burden of dietary therapy on elderly patients with diabetes mellitus]. 886 41

The mechanism of decreased albuminuria caused by an inhibitor of angiotensin converting enzyme (ACE) was investigated in patients with early diabetic nephropathy. The subjects were 10 patients with non-insulin-dependent diabetes mellitus without azotemia but with albuminuria (less than 650 mg/day). First, a two-week study was done: one week with a diet with ordinary sodium levels and one week with a sodium-restricted diet, in random order. The systemic blood pressure and urinary excretion of sodium and albumin were measured daily. Intrarenal hemodynamics, in terms of the resistance of afferent and efferent arterioles (RA and RE) and glomerular capillary pressure (PGC), were calculated from renal clearance, the plasma total protein concentration, and the pressure-natriuresis relationship. Results obtained before and two weeks after starting the ACE inhibitor cilazapril (2 mg/day) were compared. Urinary excretion of albumin was decreased by cilazapril in 8 of the 10 patients. Cilazapril decreased the RE [6830 (3680, 14,750) to 4660 (1750, 10,790) dynes.sec.cm-5, P < 0.05, mean (minimum, maximum)] and PGC (53 +/- 5 to 43 +/- 9 mm Hg, P < 0.02, mean +/- SD) in these 8 patients, but not in the two other patients. The RA was not significantly changed in any patient. The percent change caused by cilazapril in the urinary excretion of albumin was significantly correlated with the change in PGC (N = 10, r = 0.875, P < 0.01), but not with changes in the systemic blood pressure. In conclusion, the mechanism by which an ACE inhibitor caused a short-term decrease in albuminuria in early diabetic nephropathy involved a glomerular hemodynamic change, namely, a decrease in PGC.
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PMID:Mechanism of decreased albuminuria caused by angiotensin converting enzyme inhibitor in early diabetic nephropathy. 940 58

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) plays a critical role in regulating multiple aspects of energy metabolism, including adaptive thermogenesis, mitochondrial biogenesis, and fatty acid beta-oxidation. Recently, this coactivator of nuclear receptors/transcription factors has been shown to control hepatic gluconeogenesis, an important component of the pathogenesis of both type-1 and type-2 diabetes. We described here the cloning of a novel bona fide homologue of PGC-1, PGC-1beta (PGC-1 was renamed as PGC-1alpha), first identified through searches of new data base entries. Despite the fact that PGC-1alpha and -1beta share similar tissue distributions with highest levels of expression in brown fat and heart, their mRNAs are differentially regulated in the brown adipose tissue upon cold exposure and during brown fat cell differentiation. Like PGC-1alpha, PGC-1beta mRNA levels are increased significantly in the liver during fasting, suggesting a possible role for this factor in the regulation of hepatic gluconeogenesis and/or fatty acid oxidation. Consistent with this, PGC-1beta was shown to physically interact and potently coactivate hepatic nuclear factor 4 and peroxisome proliferator-activated receptor alpha, nuclear receptors that are essential for hepatic adaptation to fasting. Finally, using sequence comparisons between PGC-1alpha and -1beta, we have identified a conserved amino acid motif that serves as a docking site for host cell factor, a cellular protein implicated in cell cycle regulation and viral infection. HCF is shown to bind to both PGC-1alpha and -1beta and augment their transcriptional activity.
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PMID:Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta ), a novel PGC-1-related transcription coactivator associated with host cell factor. 1173 90

Because of diversities of physical, mental, and psychological functions as well as clinical and social backgrounds, comprehensive geriatric assessment (CGA) is of great importance in treating elderly diabetic patients. We addressed three issues as to functions important for the CGA. First, we assessed several domains of cognitive function in 213 elderly diabetic patients. Attention and visual memory in diabetic patients without vascular disease were impaired compared with non-diabetic controls after adjusting for age and sex using analysis of covariance. Multivariate analysis revealed that age, hyperglycemia, and the presence of cerebral infarction were independent determinants for the impairment of attention in the diabetic patients. The results suggest that glucose control is important for the maintenance of cognitive function in elderly diabetic patients. Secondly, we assessed positive well-being as a measure of psychological function using a PGC morale scale in 197 elderly diabetic patients without cerebrovascular disease at baseline and examined whether the low well-being affect the development of cerebrovascular disease in a 3-year longitudinal study. The results indicate that low well-being was an independent risk factor for cerebrovascular disease after adjusting conventional risk factors in elderly diabetic patients. Thirdly, as a physical function, we assessed 5-m walking speed for both usual and maximum walking in 64 diabetic patients. The walking speed decreased with age and correlated significantly with the knee extension power and functional reach. The result suggests that muscle-strength exercise and balance training as well as endurance exercises are necessary to improve age-related decreases in walking speed and for effective exercise in elderly patients. From a gerontological point of view, new strategies of elderly diabetes treatment including muscle strength exercise and psychological approaches should be established to improve physical, mental, psychological, and social functions as assessed by the CGA.
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PMID:[Comprehensive geriatric assessment and treatment of elderly diabetic patients]. 1218 2

The nuclear co-activator PGC-1alpha is a pivotal regulator of numerous pathways controlling both metabolism and overall energy homeostasis. Inappropriate increases in PGC-1alpha activity have been linked to a number of pathological conditions including heart failure and diabetes mellitus. Previous studies (Puigserver, P., Adelmant, G., Wu, Z., Fan, M., Xu, J., O'Malley, B., and Spiegelman, B. M. (1999) Science 286, 1368-1371) have demonstrated an inhibitory domain within PGC-1alpha that limits transcriptional activity. Using this inhibitory domain in a yeast two-hybrid screen, we demonstrate that PGC-1alpha directly associates with the orphan nuclear receptor estrogen-related receptor-alpha (ERR-alpha). The binding of ERR-alpha to PGC-1alpha requires the C-terminal AF2 domain of ERR-alpha. PGC-1alpha and ERR-alpha have a similar pattern of expression in human tissues, with both being present predominantly in organs with high metabolic needs such as skeletal muscle and kidney. Similarly, we show that in mice physiological stimuli such as fasting coordinately induces PGC-1alpha and ERR-alpha transcription. We also demonstrate that under normal conditions PGC-1alpha is located within discrete nuclear speckles, whereas the expression of ERR-alpha results in PGC-1alpha redistributing uniformly throughout the nucleoplasm. Finally, we show that the expression of ERR-alpha can dramatically and specifically repress PGC-1alpha transcriptional activity. These results suggest a novel mechanism of transcriptional control wherein ERR-alpha can function as a specific molecular repressor of PGC-1alpha activity. In addition, our results suggest that other co-activators might also have specific repressors, thereby identifying another layer of combinatorial complexity in transcriptional regulation.
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PMID:Identification of a specific molecular repressor of the peroxisome proliferator-activated receptor gamma Coactivator-1 alpha (PGC-1alpha). 1239 57

Hepatic gluconeogenesis is absolutely required for survival during prolonged fasting or starvation, but is inappropriately activated in diabetes mellitus. Glucocorticoids and glucagon have strong gluconeogenic actions on the liver. In contrast, insulin suppresses hepatic gluconeogenesis. Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. Using wild-type and mutant alleles of FOXO1, here we show that PGC-1alpha binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1alpha. Insulin suppresses gluconeogenesis stimulated by PGC-1alpha but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis.
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PMID:Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. 1702 43

Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator that regulates multiple aspects of cellular energy metabolism, including mitochondrial biogenesis, hepatic gluconeogenesis, and beta-oxidation of fatty acids. PGC-1alpha mRNA levels are increased in both type-1 and type-2 diabetes and may contribute to elevated hepatic glucose production in diabetic states. We have recently described PGC-1beta, a novel transcriptional coactivator that is a homolog of PGC-1alpha. Although PGC-1beta shares significant sequence similarity and tissue distribution with PGC-1alpha, the biological activities of PGC-1beta in the regulation of cellular metabolism is unknown. In this study, we used an adenoviral-mediated expression system to study the function of PGC-1beta both in cultured hepatocytes and in the liver of rats. PGC-1beta, like PGC-1alpha, potently induces the expression of an array of mitochondrial genes involved in oxidative metabolism. However, in contrast to PGC-1alpha, PGC-1beta poorly activates the expression of gluconeogenic genes in hepatocytes or liver in vivo, illustrating that these two coactivators play distinct roles in hepatic glucose metabolism. The reduced ability of PGC-1beta to induce gluconeogenic genes is due, at least in part, to its inability to physically associate with and coactivate hepatic nuclear receptor 4alpha (HNF4alpha) and forkhead transcription factor O1 (FOXO1), two critical transcription factors that mediate the activation of gluconeogenic gene expression by PGC-1alpha. These data illustrate that PGC-1beta and PGC-1alpha have distinct arrays of activities in hepatic energy metabolism.
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PMID:PGC-1beta in the regulation of hepatic glucose and energy metabolism. 1280 85

beta cell dysfunction is an important component of type 2 diabetes, but the molecular basis for this defect is poorly understood. The transcriptional coactivator PGC-1alpha mRNA and protein levels are significantly elevated in islets from multiple animal models of diabetes; adenovirus-mediated expression of PGC-1alpha to levels similar to those present in diabetic rodents produces a marked inhibition of glucose-stimulated insulin secretion from islets in culture and in live mice. This inhibition coincides with changes in metabolic gene expression associated with impaired beta cell function, including the induction of glucose-6-phosphatase and suppression of GLUT2, glucokinase, and glycerol-3-phosphate dehydrogenase. These changes result in blunting of the glucose-induced rise in cellular ATP levels and membrane electrical activity responsible for Ca(2+) influx and insulin exocytosis. These results strongly suggest that PGC-1alpha plays a key functional role in the beta cell and is involved in the pathogenesis of the diabetic phenotype.
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PMID:Suppression of beta cell energy metabolism and insulin release by PGC-1alpha. 1285 53

Insulin resistance increases and muscle oxidative capacity decreases during aging, but lifestyle changes-especially physical activity-may reverse these trends. Here we report the effect of a 16-week aerobic exercise program (n = 65) or control activity (n = 37) performed by men and women aged 21-87 years on insulin sensitivity and muscle mitochondria. Insulin sensitivity, measured by intravenous glucose tolerance test, decreased with age (r = -0.32) and was related to abdominal fat content (r = -0.65). Exercise increased peak oxygen uptake (VO(2peak); 10%), activity of muscle mitochondrial enzymes (citrate synthase and cytochrome c oxidase, 45-76%) and mRNA levels of mitochondrial genes (COX4, ND4, both 66%) and genes involved in mitochondrial biogenesis (PGC-1alpha, 55%; NRF-1, 15%; TFAM, 85%). Exercise also increased muscle GLUT4 mRNA and protein (30-52%) and reduced abdominal fat (5%) and plasma triglycerides (25%). None of these changes were affected by age. In contrast, insulin sensitivity improved in younger people but not in middle-aged or older groups. Thus, the muscle mitochondrial response to 4 months of aerobic exercise training was similar in all age-groups, although the older people did not have an improvement in insulin sensitivity.
Diabetes 2003 Aug
PMID:Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. 1288 2


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