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

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new diabetic strain of rats whose disease closely resembles human type 2 diabetes. We measured plasma adrenocorticotropic hormone (ACTH) and corticostrone levels, and iodine-125-labeled ovine corticotropin-releasing factor ([125I]oCRF) binding in the anterior pituitary after ether-laparotomy stress in OLETF rats to examine the alteration of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, we examined ACTH secretion following CRF administration in vivo and in vitro to characterize the mechanisms regulating the HPA axis in OLETF rats. Body weight, plasma glucose and insulin levels in OLETF rats were significantly higher than that in Long-Evans Tokushima Otsuka (LETO) rats. Basal plasma ACTH levels tended to be higher in OLETF rats than in LETO but it did not reach statistical significance. Ether-laparotomy stress dramatically increased plasma ACTH levels at 2 h after the stress both in either OLETF and LETO rats; the peak plasma ACTH level in OLETF rats following the stress was significantly greater than in LETO rats. Plasma ACTH levels following CRF (2 microg/kg, i.v.) in OLETF and LETO rats showed statistically significant increases at 10 and 30 min after CRF administration compared to ACTH levels at 0 min, however, the peak plasma ACTH level in OLETF rats at 10 min after CRF administration was significantly greater than in LETO rats. In contrast to ACTH levels, no significant differences in corticosterone levels between OLETF and LETO were observed at any of the time points. CRF (10 ng/ml) significantly increased ACTH secretion in pituitary cultures from OLETF compared to LETO rats. These data reveal a complex regulation of the endocrine system in this diabetic condition and suggest that HPA axis may be more stimulated during acute stress in diabetes mellitus than in unaffected subjects.
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PMID:Increased adrenocorticotropin responses to acute stress in Otsuka Long-Evans Tokushima Fatty (type 2 diabetic) rats. 1066 2

Diabetes mellitus is one of the most frequent metabolic syndromes found in our hospitals, occurring at around 10%. There are basically two types: the most common is Type 2, associated with obesity in almost 80% of cases and family groupings, and then, far behind, comes Type 1 which requires insulin administration for life. Furthermore, there is a condition known as "stress hyperglycaemia" in which a patient without a prior history of diabetes mellitus responds to stress with a syndrome comprising hypermetabolism, hyperglycaemia, hyperlactacidaemia and protein catabolism. The desirable pre-prandial levels of glycaemia in an outpatient are between 80 and 120 mg/dl (under 100 mg/dl is normal) and between 100 and 140 mg/dl before retiring (levels of 110 mg/dl are normal). In patients with artificial nutrition, whether parenteral or enteral, the control of glycaemia is not so strict and the recommendation is for a level of around 150-200 mg/dl in the acute stress phases, falling to 100-150 mg/dl in stable patients. The ideal enteral formula for diabetic patients has been a bone of contention for years and has still not been satisfactorily resolved. The discussion centres on the replacement of saturated fatty acids by mono-unsaturated fatty acids (MUFA) or by carbohydrates. The studies of patients undergoing prolonged treatments with MUFA-rich enteral diets have shown a greater control of glycaemia with these diets than with those rich in carbohydrates, so Type 2 diabetics and in stress hyperglycaemia with enteral nutrition, there is an ever stronger proposal to use MUFA rich formulas, whereas in Type 1 diabetics and in Type 2 patients with high prior requirements of insulin, it would be more recommendable to use diets with a more intermediate composition. With regard to parenteral nutrition, there is a consensus on increasing the amount of fatty acids to the detriment of carbohydrates, but the use of carbohydrates other than glucose is not so clear. The use of fast-acting insulin, either intravenously or subcutaneously, is recommended in the acute stages of the underlying condition because any instability in the patient makes it difficult to plan the required dose of intermediate-acting NPH insulin. The use of metformin or acarbose is not recommended. In parenteral nutrition, the subcutaneous administration of NPH insulin is often required at doses of 30% of the home dosage as the basal insulin therapy in addition to fast-acting insulin in the nutrition bag and a regimen of subcutaneous fast-acting insulin every 6 hours depending on glycaemia.
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PMID:[Diabetes and nutrition]. 1122 4

Activated peripheral T-lymphocytes are increased in both pre-insulin-dependent diabetes mellitus (IDDM) patients and in recently diagnosed IDDM patients, as well as in various forms of acute stress. We studied the in vivo T-lymphocyte activation in six patients in severe diabetic ketoacidosis (DKA) prior to treatment, after 24 h of treatment and > or =5 days after admission. Five of the six patients showed an increased percentage of activated T-lymphocytes based on the expression of HLA-DR at 24 h of treatment when compared to the admission percentage of activation (P<.05). There was no correlation to the admission serum glucose, osmolality, or electrolytes. Serum pH showed a trend toward an inverse correlation, but was not statistically significant. We speculate that T-lymphocyte activation plays a role in the progression of the acute complications of subclinical brain edema and interstitial pulmonary edema of DKA. This process could also be another factor in the progression of the chronic complications of IDDM in addition to the well-established effects of hyperglycemia and hypertension.
J Diabetes Complications
PMID:Acute activation of peripheral lymphocytes during treatment of diabetic ketoacidosis. 1135 83

In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus for the compensation. We provide evidence from cross-sectional, longitudinal, and prospective data from Pima Indians (n = 413) and Caucasians (n = 60) that fasting and postprandial glucose concentrations increase with decreasing M despite normal compensation of AIR. For this physiologic adaptation to chronic stress (insulin resistance), we propose to use the term "glucose allostasis." Allostasis (stability through change) ensures the continued homeostatic response (stability through staying the same) to acute stress at some cumulative costs to the system. With increasing severity and over time, the allostatic load (increase in glycemia) may have pathological consequences, such as the development of type 2 diabetes.
Diabetes 2003 Apr
PMID:Glucose allostasis. 1266 59

There is growing evidence that stress contributes to cardiovascular disease. Chronic stress contributes to the atherosclerotic process through increased allostatic load, which is mediated by the neuroendocrine and immune systems (sympathetic nervous system and hypothalamus-pituitary adrenal axis) and related chronic risk factors (insulin resistance syndrome, hypertension, diabetes, and hyperlipidemia). In addition, acute stress can trigger cardiovascular events predominantly through sympathetic nervous activation and potentiation of acute risk factors (blood pressure increase, endothelial cell dysfunction, increased blood viscosity, and platelet and hemostatic activation). Earthquakes provide a good example of naturally occurring acute and chronic stress, and in this review we focus mainly on the effects of the Hanshin-Awaji earthquake on the cardiovascular system. The Hanshin-Awaji earthquake resulted in a 3-fold increase of myocardial infarctions in people living close to the epicenter, particularly in women, with most of the increase occurring in nighttime-onset events. There was also a near doubling in the frequency of strokes. These effects may be mediated by changes in hemostatic factors, as demonstrated by an increase of D-dimer, von Willebrand factor, and tissue-type plasminogen activator (tPA) antigen. Blood pressure also increased after the earthquake, and was prolonged for several weeks in patients with microalbuminuria.
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PMID:Disasters and the heart: a review of the effects of earthquake-induced stress on cardiovascular disease. 1288 26

Diabetic ketoacidosis (DKA) may be defined as a metabolic derangement characterized by hyperglycemia, acidosis and ketonuria. It is a crucial pediatric medical emergency. DKA may occur in children with diabetes at onset due to severe insulin deficiency, in established patients from failing to take insulin, acute stress, and poor sick-day management. The treatment of DKA has undergone a radical transformation over recent years. Among the major innovations the early adjustment of the hydroelectrolyte imbalance and the continuous i.v. infusion of microdoses of insulin are the most interesting. Despite appropriate use of insulin and fluids, and continuous clinical observation, the mortality rate has not improved, and has remained the same as that reported in the 1970s. DKA can be prevented by shortening the period of carbohydrate intolerance that usually precedes the diagnosis of Type 1 diabetes. Its prevention decreases morbidity and mortality and allows to save on the hospital costs. The aim of this paper is to review the main aspects of the treatment and prevention of DKA.
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PMID:Treatment of diabetic ketoacidosis in children and adolescents. 1505 15

The glucose disposal effect of insulin after a meal is accounted for in approximately equal measure by the direct action of insulin and the action of HISS (hepatic insulin sensitizing substance) released from the liver and acting on skeletal muscle to stimulate glucose storage as glycogen. The ability of insulin to cause HISS release is determined by hepatic parasympathetic nerves. Eliminating the parasympathetic signal by surgical denervation of the liver or by blockade of hepatic muscarinic receptors, hepatic nitric oxide synthase, or hepatic cyclooxygenase results in insulin resistance that can be accounted for by the absence of HISS action and is referred to as HISS-dependent insulin resistance (HDIR). Animal models in which the insulin resistance has been shown to be HDIR includes the spontaneously hypertensive rat, sucrose fed rats, animals with liver disease, adult offspring of fetal alcohol exposure, acute stress, and ageing. We suggest that HDIR accounts for the major metabolic disturbances in type 2 diabetes, including the postprandial hyperglycemia that results in the majority of pathologies related to diabetes. The observation of meal-induced insulin sensitization (MIS) and the role of HISS allows for consideration of a new paradigm relating meal processing, diabetes, obesity, and insulin resistance. New diagnostic approaches and therapeutic targets are described.
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PMID:A new paradigm for diabetes and obesity: the hepatic insulin sensitizing substance (HISS) hypothesis. 1515 45

The hypothalamo-pituitary-adrenal (HPA) axis is a key component of the stress reaction. Most contemporary reviews mention the corticotropin-releasing hormone and arginine vasopressin (AVP)-containing parvocellular neurons of the hypothalamic paraventricular nucleus as the endocrinomotor component of the system. Although there are many studies about the role of AVP in the stress activation, there is evidence consistent and inconsistent with the general view on the importance of AVP. We propose a list of experiments that may provide critical evidence for or against the widely held opinion. The naturally AVP-deficient Brattleboro rat seems to be a good tool for studying the role of AVP. Our experiments on Brattleboro rats with restraint and ip hypertonic saline injection did not support the prominent role of AVP in acute stress, although in forced swim the lack of AVP influenced the HPA axis activation. Among different chronic stress situations (14 days' restraint, chronic morphine or ip hypertonic saline treatment, streptozotocin-induced diabetes mellitus), the role of AVP was not confirmed by changes in somatic parameter (i.e., body, thymus, and adrenal weight changes).
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PMID:The role of vasopressin in hypothalamo-pituitary-adrenal axis activation during stress: an assessment of the evidence. 1524 Mar 64

Chronic diabetes mellitus (DM) induces hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA). Our present study addresses the role of vasopressin (AVP) in maintaining adrenocortical responsiveness during DM. AVP-deficient mutant Brattleboro rats were used with heterozygous controls and the V2 agonist, desmopressin was infused to replace peripheral AVP. To induce DM the rats were injected by streptozotocin (STZ, 60 mg/ml/kg i.v.) and studied 2 weeks later. The acute stress stimulus was 60 min restraint. The signs of DM (the increase in water consumption and in blood glucose levels) were discovered in all rats. The diuretic effect of the lack of AVP was additional to the DM-induced osmotic diuresis. DM induced significant, chronic stress-like somatic changes on which AVP-deficiency had no effect and although desmopressin infusion normalized the water consumption and the body weight gain in AVP-deficient rats, it had no effect on DM-induced changes. The acute stress-induced plasma ACTH elevation was smaller in AVP-deficient or DM rats but these effects were not additive. Desmopressin did not normalize the decreased ACTH-elevation of AVP-deficient animals. The resting morning plasma corticosterone level was elevated both in DM and AVP-deficient rats without interaction. The restraint-induced corticosterone rise was influenced neither by the lack of AVP nor by DM and the basal and stress-induced prolactin levels were smaller in DM rats without any effect of AVP-deficiency. In conclusion, our data suggest that AVP does not play a crucial role in HPA axis regulation during DM-induced chronic stress. In contrast, the role of AVP seems to be more important during acute stress, however, it is restricted to the ACTH regulation. According to the water consumption data diabetes insipidus seems to be an additional risk factor for DM.
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PMID:The role of vasopressin in diabetes mellitus-induced hypothalamo-pituitary-adrenal axis activation: studies in Brattleboro rats. 1646 84

There is growing recognition that the O-linked attachment of N-acetyl-glucosamine (O-GlcNAc) on serine and threonine residues of nuclear and cytoplasmic proteins is a highly dynamic post-translational modification that plays a key role in signal transduction pathways. Numerous proteins have been identified as targets of O-GlcNAc modifications including kinases, phosphatases, transcription factors, metabolic enzymes, chaperons, and cytoskeletal proteins. Modulation of O-GlcNAc levels has been shown to modify DNA binding, enzyme activity, protein-protein interactions, the half-life of proteins, and subcellular localization. The level of O-GlcNAc is regulated in part by the metabolism of glucose via the hexosamine biosynthesis pathway (HBP), and the metabolic abnormalities associated with insulin resistance and diabetes, such as hyperglycemia, hyperlipidemia, and hyperinsulinemia, are all associated with increased flux through the HBP and elevated O-GlcNAc levels. Increased HBP flux and O-GlcNAc levels have been implicated in the impaired relaxation of isolated cardiomyocytes, blunted response to angiotensin II and phenylephrine, hyperglycemia-induced cardiomyocyte apoptosis, and endothelial and vascular cell dysfunction. In contrast to these adverse effects, recent studies have also shown that O-GlcNAc levels increase in response to acute stress and that this is associated with increased cell survival. Thus, while the relationship between O-GlcNAc levels and cellular function is complex and not well-understood, it is clear that these pathways play a critical role in the regulation of cell function and survival in the cardiovascular system and may be implicated in the adverse effects of metabolic disease on the heart.
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PMID:Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system. 1697 Sep 29


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