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

In summary, our data suggest that in uncontrolled diabetes, increased HPA activity is caused by increased central drive at or above the level of the PVN. Insulin treatment only restores HPA activity at and below the pituitary level, presumably by GC-mediated suppression of ACTH secretion. We hypothesize that the defective HPA response to hypoglycaemia is at least in part due to a lack of a decrease in MR mRNA in response to hypoglycaemia, and diminished sensitivity of the pituitary and adrenal gland to stimulation. Interestingly, insulin treatment restores the HPA response, but not the defective epinephrine response. Therefore, defective epinephrine responses are not linked to defective HPA responses. Similarly, antecedent hypoglycaemia specifically impairs epinephrine responses, but not HPA responses to hypoglycaemia. These studies have revealed some of the mechanisms of impaired HPA function in diabetes and its impaired responsiveness to hypoglycaemia. Further investigations are essential for understanding poor counterregulation in insulin-treated diabetes and may lead to new strategies for preventing hypoglycaemia.
Diabetes Nutr Metab 2002 Oct
PMID:Mechanisms of impaired hypothalamic-pituitary-adrenal (HPA) function in diabetes: reduced counterregulatory responsiveness to hypoglycaemia. 1262 83

The auditory system is permanently open - even during sleep. Its quick and overshooting excitations caused by noise signals are subcortically connected via the amygdala to the hypothalamic-pituitary-adrenal-axis (HPA-axis). Thus noise causes the release of different stress hormones (e.g. corticotropin releasing hormone: CRH; adrenocorticotropic hormone: ACTH) especially in sleeping persons during the vagotropic night/early morning phase. These effects occur below the waking threshold of noise and are mainly without mental control. Animal experiments show noise-induced changes in sensitivity of cellular cortisol receptors by increase of heat-shock proteins, and ultrastructural changes in the tissue of the heart and the adrenal gland. Increased cortisol levels have been found in humans when exposed to aircraft noise or road traffic noise during sleep. The effects of longer-lasting activation of the HPA-axis, especially long term increase of cortisol, are manifold: immuno suppression (e.g. eosinopenia), insulin resistance (e.g. diabetes), cardiovascular diseases (e.g. hypertension and arteriosclerosis), catabolism (e.g. ostoeporosis), intestinal problems (e.g. stress ulcer) etc. Even worse may be the widespread extrahypothalamical effects of CRH/and/or ACTH which have the potential to influence nearly all regulatory systems, causing for example stress-dysmenorrhea etc. as signs of disturbed hormonal balance.
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PMID:Possible health effects of noise induced cortisol increase. 1268 72

Visceral obesity represents an important risk factor associated with hypertension, diabetes and cardiovascular diseases. Since this condition is associated with a disruption of the functioning of the HPA axis, stress-induced HPA axis activation has been identified to play an important role in this preferential body fat accumulation. HPA axis activation increases cortisol (corticosterone) production which has been shown to exert hyperphagic and antithermogenic effects. Since abdominal adipose tissue has more cells per mass units, higher blood flow and more glucocorticoid receptors, glucocorticoids affect abdominal fat to a greater extent than subcutaneous adipose tissue. Cushing's syndrome in humans is the best evidence showing a link between hypercortisolemia and accumulation of central fat. The Hervey's hypothesis which suggests that fat cells take up and catabolize glucocorticoids is one of the possible regulatory effect that supports the adaptive role of visceral fat in response to stress. This is also supported by other evidence showing that abdominal obesity is associated with an increased cortisol clearance. Hormonal and enzymatic changes have been implicated in this preferential body fat accumulation in response to stress. Specific genetic background may also accentuate this visceral fat accumulation in some individuals exposed to stress. Alternatively, obesity could also be a source of stress promoting the visceral fat accumulation since visceral fat is able to release cytokines which stimulate the HPA axis. Even if the available literature does not permit to establish clearly which comes first, it suggests that visceral obesity could represent a non optimal physiological adaptation to stress. In this context, visceral obesity treatment should focus on stress management and weight loss strategies in order to stop this vicious circle.
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PMID:Is visceral obesity a physiological adaptation to stress? 1461 17

mRNA levels of kinin B1 and B2 receptors were determined in HPA axis of type 1 (STZ-induced) and type 2 diabetic rats (ZDF and obese Zucker rats). B2 mRNA levels were elevated in hypothalamus of STZ-induced diabetic (STZ-D) and ZDF rats. Pituitary B2 mRNA levels were elevated in ZDF and obese rats. Adrenal B2 mRNA level was attenuated in STZ-D rats. Kinin B1 receptor may not play a role in HPA axis in diabetes since its expression was unchanged. Enhanced mRNA expression of B2 receptors in hypothalamus of STZ-D and ZDF rats parallels a rise in plasma glucose and reflect a functional relationship. Enhanced pituitary B2 mRNA in type 2 and reduced adrenal in type 1 diabetes account for a differential pattern in release of transmitters.
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PMID:Expression of kinin receptor mRNA in the HPA axis of type 1 and type 2 diabetic rats. 1517 Dec 37

Prolonged exposure to stress and the resulting over-stimulation of the HPA system are often detrimental to the homeostasis of an organism. In fact, chronic stress is believed to affect the pathology of several disease states including coronary heart disease and hypertension, diabetes and obesity. In humans, mutations in the GLC1A gene have been associated with primary open angle glaucoma. Previous studies on this gene have suggested that its expression is also affected by the same factors that mediate the stress response. With the ultimate goal of using the nematode, Caenorhabditis elegans, as an invertebrate model for glaucoma, we have measured the stress responsiveness of the cof-2 gene, one of two C. elegans proteins with significant homology to the myocilin olfactomedin domain. We show that both cof-2 mRNA and protein expression are developmentally regulated and that both are affected by heat shock stress.
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PMID:Glaucoma studies in the eyeless worm: stress responsiveness and temporal expression of the Caenorhabditis elegans myocilin-like gene, cof-2. 1564 Nov 63

Conflicting results of an association of the human platelet antigen 1b (HPA-1b/PlA2), localized on the beta-subunit of the integrin alpha(IIb)beta3, and the alpha(2)807TT genotype of the integrin alpha2beta1 with coronary atherosclerosis and myocardial infarction have been reported. Both platelet receptor polymorphisms were genotyped in 3261 patients who had undergone coronary angiography, including 1175 survivors of a myocardial infarction, 1211 individuals with coronary artery disease but no history of myocardial infarction, and 571 control patients without angiographic coronary artery disease, and in 793 blood donors. In a case-control design, the prevalence of HPA-1b and alpha(2)807TT genotypes did not differ significantly between the patient groups with coronary artery disease or myocardial infarction and patient controls or blood donors. By contrast, using a multivariate case-only design, it was found that the median age of onset of myocardial infarction was 5.2 years earlier (P = 0.006) in carriers of the HPA-1b allele and 6.3 years earlier (P = 0.006) in carriers of the alpha(2)807TT genotype in the 264 survivors of myocardial infarction of recent onset with one- or two-vessel coronary artery disease. A significant interaction with the conventional risk factors hypercholesterolemia, smoking, diabetes, hypertension, and hyperfibrinogenemia was excluded. Human platelet antigen 1b and alpha(2)807TT are associated with premature myocardial infarction but not with coronary artery disease, suggesting a role of distinct integrin genotypes for increased platelet thrombogenicity. This association requires confirmation in follow-up studies.
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PMID:Association of polymorphisms of platelet membrane integrins alpha IIb(beta)3 (HPA-1b/Pl) and alpha2(beta)1 (alpha807TT) with premature myocardial infarction. 1597 10

Inflammation is frequently present in the visceral fat and vasculature in certain patients with cardiovascular disease (CVD) and/or adult onset Diabetes Mellitus Type II (NIDDM). An hypothesis is presented which argues that repeated acute or chronic psychologically stressful states may cause this inflammatory process. The mediators are the major stress hormones norepinephrine (NE) and epinephrine (E) and cortisol together with components of the renin-angiotensin system (RAS), the proinflammatory cytokines (PIC), as well as free fatty acids (ffa), the latter as a result of lipolysis of neutral fat. NE/E commence this process by activation of NF(kappa)B in macrophages, visceral fat, and endothelial cells which induces the production of toll-like receptors which, when engaged, produce a cascade of inflammatory reactions comprising the acute phase response (APR) of the innate immune system (IIS). The inflammatory process is most marked in the visceral fat depot as well as the vasculature, and is involved in the metabolic events which culminate in the insulin resistance/metabolic syndromes (IRS/MS), the components of which precede and comprise the major risk factors for CVD and NIDDM. The visceral fat has both the proclivity and capacity to undergo inflammation. It contains a rich blood and nerve supply as well as proinflammatory molecules such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), leptin, and resistin, the adipocytokines, and acute phase proteins (APP) which are activated from adipocytes and/or macrophages by sympathetic signaling. The inflammation is linked to fat accumulation. Cortisol, IL-6, angiotensin II (angio II), the enzyme 11(beta) hydroxysteroid dehydrogenase-1 and positive energy balance, the latter due to increased appetite induced by the major stress hormones, are factors which promote fat accumulation and are linked to obesity. There is also the capacity of the host to limit fat expansion. Sympathetic signaling induces TNF which stimulates the production of IL-6 and leptin from adipocytes; these molecules promote lipolysis and ffa fluxes from adipocytes. Moreover, catecholamines and certain PIC inhibit lipoprotein lipase, a fat synthesizing enzyme. The brain also participates in the regulation of fat cell mass; it is informed of fat depot mass by molecules such as leptin and ffa. Leptin stimulates corticotrophin releasing hormone in the brain which stimulates the SNS and HPA axes, i.e. the stress response. Also, ffa through portal signaling from the liver evoke a similar stress response which, like the response to psychologic stress, evokes an innate immune response (IIR), tending to limit fat expansion, which culminates in inflammatory cascades, the IRS-MS, obesity and disease if prolonged. Thus, the brain also has the capacity to limit fat expansion. A competition apparently exists between fat expansion and fat loss. In "western" cultures, with excessive food ingestion, obesity frequently results. The linkage of inflammation to fat metabolism is apparent since weight loss diminishes the concentration of inflammatory mediators. The linkage of stress to inflammation is all the more apparent since the efferent pathways from the brain in response to fat signals, which results in inflammation to decrease and limit fat cell mass, is the same as the response to psychologic stress, which strengthens the hypothesis presented herein.
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PMID:The inflammatory consequences of psychologic stress: relationship to insulin resistance, obesity, atherosclerosis and diabetes mellitus, type II. 1678 Oct 84

Syndrome X, the Metabolic Syndrome, and type II diabetes are closely related diseases that share risk factors and symptoms, notably insulin resistance. Several factors have been proposed either to mediate the disease(s) or to be their causes, and most converge on the endocrine/paracrine functions of the adipocyte. A common feature of such systems is their relative autonomy from systemic negative feedback regulation, for example by the HPA axis. We draw particular attention to two such mechanisms, both of which are associated with, and can cause, insulin resistance: the extra-adrenal production of corticosteroids, and the tissue renin angiotensin system of the adipocyte. These show another feature: the inter-regulation of glucocorticoid action and the RAS by positive feedback. Cortisol enhances the expression of 11 beta-HSD 1, and also of angiotensinogen and angiotensin type 1 receptors. In turn, angiotensin can stimulate further corticosteroid production, from the adrenal and perhaps from extra-adrenal sources. The instability inherent in such positive loops could account for the progressive nature of the disease(s), suggesting ways to break the circle.
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PMID:Angiotensin II, corticosteroids, type II diabetes and the metabolic syndrome. 1713 48

The interaction between genetic constitution and in utero environment determines fetal growth and development and influences the susceptibility to certain disorders in adulthood. Data from both animal and human studies indicate that prenatal and early postnatal malnutrition can program the hypothalamus-pituitary-adrenal axis (HPA axis), altering neuroendocrine response to stressors throughout lifetime. Impaired uteroplacental perfusion results in fetal growth restriction (FGR). In FGR there is evidence of chronic hypoxemia and alterations in metabolic, endocrine, and hematological parameters, compatible with starvation. Furthermore, FGR is associated with increased perinatal mortality and in the survivors there is increased susceptibility to diabetes and cardiovascular disease in adulthood. There is evidence that early postnatal growth acceleration, which would normally be considered desirable, may exacerbate metabolic dysfunction in later life.
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PMID:Fetal growth restriction and postnatal development. 1730 57

Numerous studies have demonstrated that low birth weight (LBW) is associated with the development of medical conditions, such as hypertension and diabetes, and psychiatric disorders, such as depression. One possible mechanism through which LBW might increase risk for both medical and psychiatric disorders is by altering the biologic systems (such as the hypothalamic-pituitary-adrenal [HPA] axis function) that govern emotion regulation and physical reactivity. In this study, we conducted secondary data analyses in a longitudinal study originally designed to understand the intergenerational transmission of major depressive disorder (MDD). We examined the risk for both medical and psychiatric illnesses known to be influenced by HPA axis dysregulation in the context of parental depression. The study had 2 primary objectives: (1) to examine whether LBW increases the risk of selected adult illness that may be influenced by the HPA axis and (2) to examine whether the increased risk of illness varies by parental depression status. We conducted longitudinal assessments of 244 offspring of depressed and nondepressed parents for more than 20 years. Psychopathology and medical illness were assessed by direct interview conducted by clinicians blind to risk status and previous diagnosis. We examined the effect of BW in 3 categories: less than 2.5 kg (LBW), 2.5-3.5 kg, and more than 3.5 kg (reference group). Offspring with LBW had a significantly increased risk of MDD, anxiety disorders, phobia, suicidal ideation, impaired functioning, allergies, and hypertension compared to those with BW exceeding 3.5 kg. The association between LBW and depression was stronger among children of depressed parents than among children of nondepressed parents, with an interaction term (BW and parental depression status) significant for MDD (P = .05), suggesting that parental depression may augment the impact of LBW on offspring depression:
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PMID:Low birth weight and risk of affective disorders and selected medical illness in offspring at high and low risk for depression. 1770 57


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