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

Children with long-standing IDDM have impaired counterregulatory responses to hypoglycemia. To determine whether children with new onset IDDM also have altered counterregulation, we studied the counterregulatory responses to hypoglycemia in twenty children with new onset IDDM (5-6 days, age 12.6 +/- 2.9 yr, mean +/- SD), and compared these responses to 47 subjects with long-standing IDDM (duration 7.8 +/- 3.6 yr, age 15.3 +/- 2.5 yr) and 21 controls (age 14.2 +/- 2.8 yr). Six new onset subjects were restudied three months later during their remission. Glucose nadir in new onset (2.7 +/- 0.1 mmol.l-1) was similar to controls (2.4 +/- 0.1 mmol.l-1), but was higher than in long-standing IDDM (2.2 +/- 0.1 mmol.l-1). Both groups of diabetic subjects had lower glucagon responses to hypoglycemia than controls (p < 0.005). Glucagon responses in new and long-standing diabetes did not differ. Epinephrine was diminished in new IDDM compared to controls (p < 0.01). Glucose recovery was faster in new onset than in long-standing IDDM (p < 0.001) and the same as in controls. Responses remained diminished 3 months after diagnosis despite increased C-peptide and lower glycosylated hemoglobin. Thus, children with IDDM have diminished counterregulatory responses to hypoglycemia at diagnosis, that are similar to those in long-standing IDDM. The reasons for this impairment and its clinical application in childhood require further investigation.
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PMID:Impaired counterregulatory hormone responses to hypoglycemia in children and adolescents with new onset IDDM. 782 Feb 18

Adrenal autoantibodies characteristic of autoimmune Addison disease are directed towards steroid 21-hydroxylase (21-OH; EC 1.14.99.10). We describe a new assay to measure 21-OH autoantibodies (21-OH Abs), based on immunoprecipitation by the antibodies of 35S-labeled human 21-OH. Using this immunoprecipitation assay (IPA), we detected 21-OH Abs in 42 of 64 (66%) patients with Addison disease and in 14 of 19 (74%) patients with autoimmune polyendocrine syndromes type I and type II. No 21-OH Abs were detected by the IPA in any patients with Addison disease attributable to tuberculosis (n = 9) or adrenoleukodystrophy (n = 9) or in patients with autoimmune thyroid disease (n = 28), systemic lupus erythematosus (n = 10), myasthenia gravis (n = 10), rheumatoid arthritis (n = 10), or insulin-dependent diabetes mellitus (n = 12). None of the 26 sera from healthy normal blood donors was positive for 21-OH Abs by the assay. We found good agreement between 21-OH Abs measured by IPA and by Western blotting (r = 0.83, n = 123, P < 0.001). The inter- and intraassay CVs for IPA were well < 10% at high, medium, and low concentrations of 21-OH Abs. Overall, our studies indicate that the IPA provides a specific, sensitive, and convenient system for measuring 21-OH Abs.
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PMID:Immunoprecipitation assay for autoantibodies to steroid 21-hydroxylase in autoimmune adrenal diseases. 788 6

To elucidate the role played by interferon-alpha (IFN alpha) in the pathogenesis of autoimmune endocrine disease, we determined the autoantibody status, thyroid function test results, hemoglobin-A1c levels, and clinical symptoms of 58 patients who received IFN alpha for treatment of chronic active type C hepatitis. Each patient was treated for 6 months with a total dose of 391 +/- 140 x 10(6) U (mean +/- SD). Thyroid microsomal and/or thyroglobulin antibodies newly appeared or were increased in titer in 6 patients, 2 of whom developed hypothyroidism during IFN alpha therapy. Neither islet cell antibodies nor insulin-dependent diabetes mellitus developed during IFN alpha therapy, although hemoglobin-A1c levels were increased in 2 patients. One patient became positive for antimitochondrial antibodies, and another patient with preexisting antimitochondrial antibodies also manifested deterioration in liver function test results. Parietal cell antibodies and smooth muscle cell antibodies were the most frequent newly developed antibodies in 7 patients. Adrenal medullary cell antibodies and nuclear antibodies newly developed in 2 and 1 patients, respectively. At least 1 of 8 autoantibodies newly appeared in 19 patients (32.8%) and hypothyroidism developed in 2 patients (3.4%) during IFN alpha therapy. On the other hand, in 19 age- and sex-matched patients who did not receive IFN alpha, no autoantibody appeared, and no autoimmune disease developed during a follow-up period of 3 months. These findings suggest that IFN alpha acts as an immunomodulatory agent, inducing autoantibody production and the development of autoimmune disease in susceptible patients. Special attention should be paid to the development of hypothyroidism during IFN alpha therapy.
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PMID:Autoimmune endocrine disease induced by recombinant interferon-alpha therapy for chronic active type C hepatitis. 788 51

We observed in the HIT cell, a clonal insulin-secreting cell line, that epinephrine and somatostatin lower insulin mRNA levels and intracellular insulin content in addition to the well-recognized effect of these hormones to inhibit insulin secretion. To determine whether these inhibitory hormones might regulate insulin synthesis at the level of insulin gene transcription, we studied HIT cell expression of a human insulin-chloramphenicol acetyl transferase (CAT) reporter gene in the presence of glucose, epinephrine, and somatostatin. HIT cell expression of this human insulin-CAT reporter gene was responsive to glucose in a concentration-dependent manner, increasing threefold as the glucose concentration increased from 0.4 to 11 mM. Epinephrine significantly inhibited insulin-CAT reporter gene expression (61 +/- 5% of control), an effect mediated specifically by the human insulin gene promoter/enhancer sequence. Somatostatin significantly inhibited expression of the human insulin-CAT reporter gene (65 +/- 4% of control) and, to a lesser extent, expression of a control reporter gene, pRSVCAT (78 +/- 4% of control). Thus, somatostatin may inhibit insulin gene transcription by insulin gene-specific effects as well as more general effects on gene expression. Both epinephrine and somatostatin inhibited expression of the human insulin-CAT reporter gene in a concentration-dependent manner that paralleled inhibition of insulin secretion. These studies indicate that epinephrine and somatostatin lower HIT cell insulin mRNA levels in part by inhibiting insulin gene transcription. Thus, hormonal inhibition of insulin secretion may be coupled with inhibition of insulin synthesis, thereby allowing the beta-cell to match insulin supply to secretory demand.
Diabetes 1994 Apr
PMID:Regulation of human insulin gene transcription by glucose, epinephrine, and somatostatin. 790 98

Adrenal tumors showing no clinical manifestations (incidentaloma) are frequently encountered during imaging analysis upon routine examinations. These tumors are sometimes associated with hypertension and/or diabetes mellitus (DM). We have examined six cases of incidentalomas with these symptoms in this study. All patients underwent endocrinological evaluation by measuring plasma cortisol and aldosterone levels to assess adrenocortical function. The levels of urinary 17-hydroxysteroids, 17-ketosteroids and catecholamines were also measured. Imaging analysis were performed by using 131I-adosterol scintigraphy, computed tomography and magnetic resonance imaging. Whereas one case was diagnosed as having an adrenal adenoma without the examination of a surgical specimen, other cases underwent surgical removal of the tumor, and final diagnoses were made by pathohistological examination of the tumors. Three cases were diagnosed as having adrenocortical adenomas (one was functioning and others were non-functioning) and one case was diagnosed as having a functional adrenocortical carcinoma. Adenomas were found to produce either non-functional steroids or a small amount of functional steroid hormones. The adenoma patients all suffered hypertension, whereas one of the adenoma patients and the carcinoma patient showed signs of DM. By contrast, of the six cases, one case was diagnosed as having an adrenal cyst, and one case was diagnosed with myelolipoma. Although these two cases suffered DM and hypertension, respectively, it seemed to be unlikely that these clinical symptoms were caused by the adrenal disease. Thus, the present analysis of the six incidentaloma patients suggests that once an adrenal incidentaloma patient with hypertension and/or DM is found, both endocrinological and imaging examinations are necessary to determine the indication of surgical treatment. This analysis supports the present consensus that non-functional adenomas whose sizes are 3cm or less and whose sizes do not change at any reevaluation period, as well as adrenal cysts and myelolipoma should not be surgically removed.
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PMID:[Endocrinological and imaging analyses of adrenal incidentalomas with hypertension and/or diabetes mellitus]. 800 91

Strict blood glucose control of pregnant women with insulin-dependent diabetes is associated with increased risk of hypoglycemia. The hormonal and circulatory responses to an acute episode of insulin-induced hypoglycemia were studied in eight pregestational and one gestational diabetic women during the last trimester of pregnancy and 8 to 12 weeks postpartum. Following an overnight fast, insulin was injected intravenously (0.1 to 0.2 IU insulin/kg). Blood samples were taken at -15, 0, 15, 30, 40, 60, 90, and 120 minutes for analyses of metabolites (glucose, nonesterified fatty acid (NEFA), glycerol, 3-hydroxybutyrate) and counterregulatory hormones (epinephrine, norepinephrine, glucagon, and cortisol). Placental scintigraphy (indium-113m) was performed in five pregnant patients before and during hypoglycemia. Both during pregnancy and postpartum, blood glucose decreased to the same low level (3.2 mmol/L) concomitantly with significant decreases in NEFA, glycerol, and 3-hydroxybutyrate. Epinephrine and norepinephrine showed significant and similar increases on both occasions in relation to hypoglycemia, although there was no response in glucagon and cortisol concentrations. Maternal heart rate was significantly higher in the pregnant compared with the nonpregnant state and increased significantly in both groups in response to hypoglycemia. Placental blood flow showed no consistent changes and was unrelated to the glucose and catecholamine responses. Fetal heart rate remained unchanged. Thus, it seems as if hormonal and circulatory responses to acute hypoglycemia are not altered in diabetic women during pregnancy.
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PMID:Hormonal, metabolic, and circulatory responses to insulin-induced hypoglycemia in pregnant and nonpregnant women with insulin-dependent diabetes. 804 92

In humans, adrenaline stimulates lipolysis, ketogenesis, thermogenesis and glycolysis and raises plasma glucose concentrations by stimulating both glycogenolysis and gluconeogenesis. The venous plasma adrenaline thresholds for these effects (410-680 pmol/l for the lipolytic and thermogenic effects and 550-1090 pmol/l for the glycemic, ketogenic and glycolytic effects) lie within the physiological venous plasma adrenaline concentration range of < 50 to approximately 1200 pmol/l under non-stressed conditions. Thus, adrenaline is undoubtedly frequently involved in the minute-to-minute regulation of these metabolic processes under conditions of daily living. In general, the extent to which the hormone is critically involved is unknown. Adrenaline is, however, known to play a secondary role in the physiology of glucose counter-regulation. Furthermore, individuals can survive in the absence of biologically active plasma adrenaline levels following bilateral adrenalectomy. Therefore, it seems likely that the hormone will be shown to play secondary roles in the regulation of lipolysis, ketogenesis and thermogenesis as well. It may well play more critical roles under stressful conditions and in pathophysiological states. Indeed, it has been shown to play a critical role in one pathophysiological state, the altered glucose counter-regulation in patients with established insulin-dependent diabetes mellitus.
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PMID:Adrenaline: a physiological metabolic regulatory hormone in humans? 812

We have demonstrated previously that spontaneously diabetic BB-Wistar rats exhibit decreased adrenal medullary catecholamine secretion in response to splanchnic nerve terminal stimulation. We hypothesized that this abnormality is caused by changes in the sensitivity of the adrenomedullary chromaffin cells to acetylcholine (ACh). To study this hypothesis, we isolated adrenal glands from control and spontaneously diabetic BB-Wistar rats, perfused them with ACh, and measured catecholamine secretion. Adrenal catecholamine release in response to ACh was significantly decreased at 2, 8, and 16 weeks after the onset of diabetes compared with age-matched, nondiabetic control rats. Catecholamine release in response to perfusion with 20 mM K+ was the same in adrenals from diabetic and control rats. The decreased responsiveness of diabetic rat adrenals to perfusion with ACh was significantly correlated with a decrease in the release of catecholamines in response to splanchnic nerve stimulation. A similar defect in catecholamine secretion was also seen in adrenals harvested from nondiabetic BB-Wistar rats following a 3-h period of acute hypoglycemia; however, the adrenal response to potassium was also decreased as was the catecholamine content of the adrenal. Conversely, nondiabetic BB-Wistar rats made diabetic with streptozocin (STZ) and maintained in a hyperglycemic state did not exhibit catecholamine hyposecretion 2 weeks after STZ administration. Collectively, the data describe decreased adrenomedullary response to cholinergic stimulation in spontaneously diabetic rats as early as 2 weeks after the onset of diabetes and that a similar, although more severe, hyposecretion occurs after acute, severe hypoglycemia.
Diabetes 1994 May
PMID:Decreased adrenal medullary catecholamine release in spontaneously diabetic BB-Wistar rats. Role of hypoglycemia. 816 51

Metabolically well controlled insulin-dependent diabetic subjects (IDDM) have deficient autonomic adrenomedullary responses to hypoglycemia. This defect, coupled with the characteristic deficient glucagon response to hypoglycemia, predisposes well-controlled IDDM subjects to an increased incidence of severe hypoglycemic episodes. In this report we describe a physically trained subject with long-duration IDDM (9 years) who was rigorously well-controlled (normal HBA1c), yet had exaggerated epinephrine responses to hypoglycemia compared with normal controls. Steady state epinephrine levels during a low-dose insulin (9 pM/kg/min) hypoglycemic clamp (2.9 +/- 0.1 mM) were approximately 2-fold higher compared with normal controls (10.6 vs. 5.5 +/- 0.7 nM). Epinephrine levels during a high-dose insulin (30 pM/kg/min) hypoglycemic clamp (2.8 +/- 0.1 mM) were also increased compared with normal controls (13.1 vs. 8.8 +/- 0.6 nM). We conclude that physical training in this metabolically well-controlled IDDM subject was associated with an augmented autonomic adrenomedullary response to hypoglycemia.
Diabetes Res Clin Pract 1994 Jan
PMID:Exaggerated epinephrine response to hypoglycemia in a physically fit, well-controlled IDDM subject. 820 Feb 95

1. Adult male Wistar rats were treated with streptozotocin (65 mg kg-1, i.p.) to induce diabetes. Subgroups of age-matched control and streptozotocin-treated rats were given daily injections of mixed brain bovine gangliosides (60 mg kg-1 body weight, i.p.). At eight weeks after treatment mesenteric arterial beds from rats in each of the four groups were isolated and perfused and the function of perivascular nerves (sympathetic and sensory-motor), endothelium and smooth muscle was assessed. 2. Values for basal tone of mesenteric beds from diabetic and diabetic-ganglioside rats were significantly lower than those of the control and control-ganglioside-treated rats. Perfusion pressures at basal tone were 25.55 +/- 0.8 (n = 11), 22.58 +/- 1.5 (n = 12), 28.42 +/- 1.6 (n = 12) and 30.67 +/- 1.9 (n = 12) mmHg for diabetic, diabetic-ganglioside, control and control-ganglioside-treated rats respectively. 3. There was no difference between the groups with respect to vasoconstrictor responses to sympathetic nerve stimulation, or to doses of noradrenaline. Vasoconstrictor responses to potassium chloride were also similar between the groups. 4. Perivascular nerve stimulation in the presence of the sympathetic blocker guanethidine (3 microM), with tone of the preparation raised with methoxamine (3-100 microM), elicited frequency-dependent vasodilatation of mesenteric arterial beds due to transmitter release from sensory-motor nerves. Sensory-motor nerve-induced vasodilator responses of mesenteric arterial beds from streptozotocin-diabetic and ganglioside-treated diabetic rats were significantly smaller than those of mesenteric beds from the controls (untreated and ganglioside-treated). Vasodilator responses to exogenously applied calcitonin gene-related peptide, the principal vasodilator transmitter released from these nerves, were not different between the groups. Vasodilator responses to the sensory neurotoxin capsaicin were also not different between the groups.5. Endothelium-dependent vasodilator responses to acetylcholine were similar between the groups as were those to the endothelium-independent vasodilator sodium nitroprusside.6. These results indicate that streptozotocin-induced diabetes produces marked impairment of sensory motor nerve function in the rat mesenteric arterial bed. The significantly lower basal perfusion pressures of mesenteric beds from diabetic rats compared to controls may be a reflection of sympathetic dysfunction, but no differences were apparent from the vasoconstrictor responses produced when sympathetic nerves were electrically stimulated. There was no evidence for changes in endothelial vasodilator function, or smooth muscle vasodilator and vasoconstrictor function. Ganglioside treatment did not modify any aspect of vascular function of mesenteric beds from streptozotocin-diabetic or control rats.
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PMID:Impaired sensory-motor nerve function in the isolated mesenteric arterial bed of streptozotocin-diabetic and ganglioside-treated streptozotocin-diabetic rats. 829 99


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