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 modulatory action of beta-adrenergic and opioidergic pathways on the cortisol response to acute stressors was investigated using gonadectomized male miniature pigs. Three types of stressors, nose-snare (NS, for 2 min. each on four occasions at 30 min. intervals); high intensity cracker blasts (CB, two blasts at 3 min intervals) and ACTH (1 i.u./kg BW, i.v.) were utilized 80 min after start of blood sampling. For assessment of cortisol blood samples were withdrawn every 20 min for 200 min. In addition, animals received i.v. injections of either isoproterenol (5 microg/ kg) or propranolol (0.5 mg/kg) or naloxone (1 mg/kg) 15 or 30 min before the application of stressor. Stress of repeated NS application as well as ACTH treatment, resulted in immediate secretion of cortisol (p<0.001). Blast of crackers resulted in a transient increase in cortisol (p<0.05). Isoproterenol stimulated the basal cortisol secretion for about 20 min in unstressed pigs (p <0.01) but propranolol had no effects. Isoproterenol also reinforced (p<0.05) the effect of CB, but had no effect on the cortisol response to nose-snare. In contrast, response to NS was reduced (p=0.02) by propranolol. Neither isoproterenol nor propranolol altered the cortisol response to ACTH application. Pretreatment with naloxone significantly increased the cortisol response to NS (p<0.01) and to CB (p<0.01), but had no effects on ACTH-induced cortisol release. In conclusion, the beta-adrenergic involvement is evident in the cortisol response to acute stress of nose-snare. Furthermore, the results indicate that activation of endogenous opioid system during stress mitigates adrenal response.
Exp Clin Endocrinol Diabetes 2007 Jun
PMID:Beta-adrenergic and opioidergic modulation of cortisol secretion in response to acute stress. 1770 79

Unlike responses to acute stressful events that are protective and adaptive in nature, chronic stress elicits neurochemical, neuroanatomical and cellular changes that may have deleterious consequences upon higher brain functioning. For example, while exposure to acute stress facilitates memory formation and consolidation, chronic stress or chronic exposure to stress levels of glucocorticoids impairs cognitive performance. Chronic stress or glucocorticoid exposure, as well as impairments in hypothalamic-pituitary-adrenal (HPA) axis function are proposed to participate in the etiology and progression of neurological disorders such as depressive illness, anxiety disorders and post-traumatic stress disorder (PTSD). HPA axis dysfunction, impaired stress responses and elevated basal levels of glucocorticoids are also hallmark features of experimental models of type 1 and type 2 diabetes, as well as diabetic subjects in poor glycemic control. Such results suggest that stress and glucocorticoids contribute to the neurological complications observed in diabetes patients. Interestingly, many of the hyperglycemia mediated changes in the brain are similar to those observed in depressive illness patients and in experimental models of chronic stress. Such results suggest that common mechanisms may be involved in the development of the neurological complications associated with Anxiety, Depressive illness and Diabetes: the As and Ds of stress. The aim of the current review will be to discuss the mechanisms through which limbic structures such as the hippocampus and amygdala respond and adapt to the deleterious consequences of chronic stress and hyperglycemia.
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PMID:The As and Ds of stress: metabolic, morphological and behavioral consequences. 1838 3

Acute ischemic stroke (AIS) results from the occlusion of an artery and causes vascular and neuronal damage, both of which affect the extent of ischemic injury and stroke outcome. Despite extensive efforts, there is only one effective treatment for AIS. Given that up to 40% of the AIS patients present with admission hyperglycemia either as a result of diabetes or acute stress response, targets for neuronal and vascular protection under hyperglycemic conditions need to be better defined. Here, we review the impact of diabetes and acute hyperglycemia on experimental stroke with an emphasis on cerebrovasculature structure and function. The relevance to clinical evidence is also discussed.
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PMID:Hyperglycemia, diabetes and stroke: focus on the cerebrovasculature. 1925 53

Compared with young adults, older adults have significantly impaired capacities to resist oxidative damage when faced with acute stress such as ischemia/reperfusion. This impairment likely contributes to increased morbidity and mortality in older adults in response to acute trauma, infections, and the susceptibility to diseases such as atherosclerosis, cancer, diabetes, and Alzheimer's disease. Consumption of foods high in polyphenols, particularly anthocyanins, have been associated with improved health, but the mechanisms contributing to these salutary effects remain to be fully established. This study tested the hypothesis that consumption of tart cherry juice containing high levels of anthocyanins improves the capacity of older adults to resist oxidative damage during acute oxidative stress. In a double-blind, placebo-controlled, crossover design, 12 volunteers [6 men and 6 women; age 69 +/- 4 y (61-75 y)] consumed in random order either tart cherry juice or placebo (240 mL twice daily for 14 d) separated by a 4-wk washout period. The capacity to resist oxidative damage was measured as the changes in plasma F(2)-isoprostane levels in response to forearm ischemia-reperfusion (I/R) before and after each treatment. The tart cherry juice intervention reduced the I/R-induced F(2)-isoprostane response (P < 0.05), whereas placebo had no significant effect. The tart cherry juice intervention also reduced basal urinary excretion of oxidized nucleic acids (8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine) (P < 0.05) but not urinary excretion of isoprostanes. These data suggest that consumption of tart cherry juice improves antioxidant defenses in vivo in older adults as shown by an increased capacity to constrain an oxidative challenge and reduced oxidative damage to nucleic acids.
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PMID:Tart cherry juice decreases oxidative stress in healthy older men and women. 1969 30

The hemoglobin A1c (HbA1c) assay provides a reliable measure of chronic glycemia and correlates well with the risk of long-term diabetes complications, so that it is currently considered the test of choice for monitoring and chronic management of diabetes. Recently, HbA1c testing has been included within the diagnostic criteria recommended for diagnosis of diabetes in nonpregnant individuals by the American Diabetes Association (ADA). The emerging concept that HbA1c can be used rather than blood glucose in the diagnosis of diabetes is highly appealing for a variety of reasons, including less sensitivity to preanalytical variables, lower within subject biological variability, little to null interference from diurnal variations, acute stress and common drugs which are known to influence glucose metabolism, as well as the fact that one single measurement might provide information for both diagnosing diabetes and tracking glycemic control. On the other hand, the use of HbA1c for screening and diagnosing diabetes also carries some limitations, including the worse diagnostic performance in different populations (i.e., pregnancy, elderly and non-Hispanic blacks), the risk of overdiagnosis in subjects with iron deficiency anemia, in subjects genetically predisposed to hyperglycation, and in those with increased red blood cell turnover. There is also a higher risk of misdiagnosis in patients with end-stage renal disease and heavy alcohol consumption. Finally, HbA1c testing might be biased due to the interference from several hemoglobin variants, is characterized by a higher imprecision than blood glucose measurement, and is more expensive. This paper will critically summarize the potential advantages and limitations of HbA1c as a recommended test for diagnosing diabetes.
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PMID:Glycated hemoglobin (HbA1c): old dogmas, a new perspective? 2046 76

Cardiovascular function is regulated at multiple levels. Some of the most important aspects of such regulation involve alterations in an ever-growing list of posttranslational modifications. One such modification orchestrates input from numerous metabolic cues to modify proteins and alter their localization and/or function. Known as the beta-O-linkage of N-acetylglucosamine (ie, O-GlcNAc) to cellular proteins, this unique monosaccharide is involved in a diverse array of physiological and pathological functions. This review introduces readers to the general concepts related to O-GlcNAc, the regulation of this modification, and its role in primary pathophysiology. Much of the existing literature regarding the role of O-GlcNAcylation in disease addresses the protracted elevations in O-GlcNAcylation observed during diabetes. In this review, we focus on the emerging evidence of its involvement in the cardiovascular system. In particular, we highlight evidence of protein O-GlcNAcylation as an autoprotective alarm or stress response. We discuss recent literature supporting the idea that promoting O-GlcNAcylation improves cell survival during acute stress (eg, hypoxia, ischemia, oxidative stress), whereas limiting O-GlcNAcylation exacerbates cell damage in similar models. In addition to addressing the potential mechanisms of O-GlcNAc-mediated cardioprotection, we discuss technical issues related to studying protein O-GlcNAcylation in biological systems. The reader should gain an understanding of what protein O-GlcNAcylation is and that its roles in the acute and chronic disease settings appear distinct.
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PMID:O-GlcNAc signaling in the cardiovascular system. 2065 Dec 94

Diabetes mellitus increases susceptibility to acute gastric injury and impairs ulcer healing. Pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARgamma) is used as anti-diabetic drug and has additionally gastroprotective activities. However, the effect of pioglitazone on the protection and healing of gastric mucosa under diabetic conditions is poorly understood. The aim of the present study was: 1) to compare the effects of treatment with PPARg ligand (pioglitazone) on healing of acetic acid-induced gastric ulcers and prevention of acute water immersion and restraint stress (WRS)-induced gastric lesions in normal rats and those with streptozotocin (STZ)-induced diabetes mellitus; 2) to assess the effects of pioglitazone on the mRNA expression of cyclooxygenase-2 (COX-2), c-NOS, interleukin-1beta and hypoxia inducible factor-1 alpha (HIF-1alpha) in the gastric mucosa of rats with or without STZ-induced diabetes mellitus; 3) to investigate the involvement of endogenous NO and proinflammatory cytokines (IL-1beta, TNF-alpha) in healing of chronic gastric ulcers and in prevention of acute stress lesions by pioglitazone in rats with or without STZ-induced diabetes mellitus. Diabetes was induced in rats by single injection of STZ (70 mg/kg i.p.) four weeks prior to production of gastric ulcers by acetic acid method or induction of stress lesions by 3.5 hours of WRS. Non-diabetic rats were used as controls. Two major animal groups (A and B) were tested; A) diabetic and non-diabetic rats with chronic gastric ulcers treated with 1) pioglitazone (40 mg/kg-d i.g.), 2) pioglitazone in combination of blocker of NO synthase (L-NNA 20 mg/kg-d i.p.), and 3) saline (vehicle-control); and B) diabetic and non-diabetic rats exposed to 3.5 hours of WRS and pretreated with 1) pioglitazone (40 mg/kg i.g.), 2) pioglitazone in combination of blocker of NO synthase (L-NNA 20 mg/kg i.p.), and 3) saline (vehicle-control). The gastric mucosal blood flow was assessed by H(2)-gas clearance method. The area of chronic acetic acid ulcers and number of acute WRS-induced gastric lesions were assessed by planimetry or by counting of number of lesions, respectively. In rats with chronic ulcers, the mRNA expression of HIF-1alpha, IL-1beta and COX-2 was assessed by RT-PCR and protein expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), COX-2 and cNOS was examined by Western blot. In rats with stress lesions, the protein expression of COX-2, cNOS, catalase, PPAR and heat shock protein 70 (HSP70) was examined by Western blot. In diabetic rats, a marked delay in ulcer healing and increased susceptibility to WRS lesions were observed and these effects were accompanied by a significant decrease in GBF. Pioglitazone significantly increased healing of chronic gastric ulcers and exerted a strong protective effect against WRS-induced lesions, but these effects were attenuated by NO-inhibition with L-NNA. Interestingly, the ulcer healing and gastroprotective effects of pioglitazone were weak under diabetic conditions, and this effect on ulcer healing was accompanied by impaired angiogenesis due to decreased PECAM-1 expression, attenuated expression of COX-2 and the increased expression of proinflammatory cytokines compared to those in diabetic rats treated with vehicle. We conclude that: 1) experimental diabetes in rats impairs healing of chronic ulcers and enhances acute stress lesions due to an increase in the expression and release of proinflammatory cytokines such as TNF-alpha and IL-1beta; 2) the ulcer healing effect of pioglitazone, which is, at least in part, mediated by endogenous NO, is significantly attenuated by L-NNA in diabetic rats despite increased COX-2 expression at the ulcer edge; 3) the formation of acute gastric lesions induced by WRS is also attenuated by pretreatment with pioglitazone due to increased GBF probably mediated by NO, as the administration of L-NNA reversed, in part, the preventive action induced by this PPARgamma ligand, and 4) pioglitazone is effective both in healing of chronic ulcers and protection against WRS lesions though its action under diabetic conditions seems to be attenuated, possibly due to reduction in NOS-NO system, angiogenesis and increased expression and release of proinflammatory cytokines.
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PMID:Gastric ulcer healing and stress-lesion preventive properties of pioglitazone are attenuated in diabetic rats. 2081 70

Chronic and acute stress, with associated pathophysiology, are implicated in a variety of disease states, with neuroimmunological dysregulation and inflammation as major hazards to health and functional sufficiency. Psychosocial stress and negative affect are linked to elevations in several inflammatory biomarkers. Immunosenescence, the deterioration of immune competence observed in the aged aspect of the life span, linked to a dramatic rise in morbidity and susceptibility to diseases with fatal outcomes, alters neuroimmunological function and is particularly marked in the neurodegenerative disorders, e.g., Parkinson's disease and diabetes. Physical exercise diminishes inflammation and elevates agents and factors involved in immunomodulatory function. Both the alleviatory effects of life-long physical activity upon multiple cancer forms and the palliative effects of physical activity for individuals afflicted by cancer offer advantages in health intervention. Chronic conditions of stress and affective dysregulation are associated with neuroimmunological insufficiency and inflammation, contributing to health risk and mortality. Physical exercise regimes have induced manifest anti-inflammatory benefits, mediated possibly by brain-derived neurotrophic factor. The epidemic proportions of metabolic disorders, obesity, and diabetes demand attention; several variants of exercise regimes have been found repeatedly to induce both prevention and improvement under both laboratory and clinical conditions. Physical exercise offers a unique non-pharmacologic intervention incorporating multiple activity regimes, e.g., endurance versus resistance exercise that may be adapted to conform to the particular demands of diagnosis, intervention and prognosis inherent to the staging of autoimmune disorders and related conditions.
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PMID:Influence of physical exercise on neuroimmunological functioning and health: aging and stress. 2095 49

Heat shock proteins (HSPs) are molecular chaperones which may act protective in cerebrovascular insults and peripheral diabetic neuropathy. We hypothesized that alpha-lipoic acid (LA), a natural thiol antioxidant, may enhance brain HSP response in diabetes. Rats with or without streptozotocin-induced diabetes were treated with LA or saline for 8 weeks. Half of the rats were subjected to exhaustive exercise to investigate HSP induction, and the brain tissue was analyzed. Diabetes increased constitutive HSC70 mRNA, and decreased HSP90 and glucose-regulated protein 75 (GRP75) mRNA without affecting protein levels. Exercise increased HSP90 protein and mRNA, and also GRP75 and heme oxygenase-1 (HO-1) mRNA only in non-diabetic animals. LA had no significant effect on brain HSPs, although LA increased HSC70 and HO-1 mRNA in diabetic animals and decreased HSC70 mRNA in non-diabetic animals. Eukaryotic translation elongation factor-2, essential for protein synthesis, was decreased by diabetes and suggesting a mechanism for the impaired HSP response related to translocation of the nascent chain during protein synthesis. LA supplementation does not offset the adverse effects of diabetes on brain HSP mRNA expression. Diabetes may impair HSP translation through elongation factors related to nascent chain translocation and subsequent responses to acute stress.
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PMID:Alpha-lipoic acid does not alter stress protein response to acute exercise in diabetic brain. 2110 31

Type 2 diabetes mellitus (T2DM), reaching epidemic proportions in humans, has emerged as a disease in aging captive populations of adult chimpanzees; however, little information is available regarding T2DM in chimpanzees. Our goals were to: (1) distinguish between normal, healthy chimpanzees and those with early (prediabetes) or advanced diabetes; (2) establish and compare the fasting (16 h) blood glucose reference range for chimpanzees at our facility with published reference ranges; and (3) establish hemoglobin A1c (HbA1c) reference intervals for healthy, nondiabetic chimpanzees and define threshold values for prediabetes and diabetes. If reliable, our reference ranges for FBG and HbA1c could become clinical tools for screening animals at risk and for monitoring therapeutic progress. The overall incidence of T2DM in our colony of 260 chimpanzees is 0.8% but is increased to 3.7% in animals older than 30 y (geriatric). For our defined reference intervals, chimpanzees with FBG or HbA1c levels up to the 85th percentile (glucose, less than or equal to 105 mg/dL; HbA1c, less than or equal to 5.0%) were considered healthy; those whose values lay between the 86th and 95th percentiles (glucose, 106 to 119 mg/dL; HbA1c, 5.1% to 5.2%) were possibly prediabetic, and animals whose values exceeded the 95th percentile (glucose, greater than or equal to 120 mg/dL; HbA1c, greater than 5.3%) were identified as potentially having diabetes. We found that our FBG range was comparable to other published results, with a positive correlation between HbA1c and glucose. Furthermore, the negligible HbA1c response to acute stress or recent food consumption suggests that HbA1c is highly useful for evaluating glycemic control during treatment of diabetic chimpanzees and is more informative concerning overall glucose control than are FBG levels alone.
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PMID:Determination of hemoglobin A1c and fasting blood glucose reference intervals in captive chimpanzees (Pan troglodytes). 2143 8


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