Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies in serums from newly diagnosed insulin-dependent (type I) diabetes mellitus (IDDM) patients and individuals experiencing early phases of beta-cell destruction specifically immunoprecipitate a minor pancreatic islet cell membrane protein of 64,000 Mr (64K). In this report, we demonstrate the use of two-dimensional (2-D) gel electrophoresis to unambiguously identify the 64K antigen. By nonequilibrium pH-gradient gel electrophoresis in the first dimension and sodium dodecyl sulphate-polyacrylamide gel electrophoresis in the second dimension, the 64K protein separates into two components, designated alpha and beta, that differ in size but display identical charge heterogeneity. The high resolution of the 2-D method efficiently separates the 64K components from background proteins in immunoprecipitates from crude detergent lysates of islets. The background proteins were identified as major cellular proteins carried nonspecifically through the immunoprecipitation procedure. The high affinity and specificity of the 64K autoantibodies were demonstrated by the exclusive and greater than 1000-fold purification of this minor protein by immunoprecipitation with IDDM serums. The 2-D analyses did not reveal additional proteins specifically immunoprecipitated by IDDM serums, suggesting that the 64K protein is the only protein antigen specifically and consistently recognized by IDDM autoantibodies in the relatively stringent conditions of immunoprecipitation. Moreover, the 2-D analyses demonstrate that purification of membrane protein fractions from both human and rat islets before the immunoprecipitation efficiently removes background proteins and substantially increases the specificity of 64K autoantibody measurements by traditional methods.
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PMID:Revelation of specificity of 64K autoantibodies in IDDM serums by high-resolution 2-D gel electrophoresis. Unambiguous identification of 64K target antigen. 267 Jun 43

It has been reported that patients with type I insulin dependent diabetes mellitus (IDDM) are characterized by reduced Na+ excretion during water immersion and saline infusion and abnormal glomerulo-tubular balance. Aims of the present study were therefore to investigate firstly the fractional tubular Na+ reabsorption during saline infusion to clarify the altered tubular site and secondly the glomerulo-tubular balance during acute increase of glomerular filtration rate induced by sodium acetoacetate infusion in IDDM. During saline and euglycaemic glucose clamp, after an overnight fast, glomerular filtration rate, renal plasma flow, filtration fraction and plasma sodium were 99 +/- 15 ml min-1 1.73 m-2, 452 +/- 109 ml min-1 1.73 m-2, 0.23 +/- 0.04 and 142 +/- 8 mmol l-1 (Mean +/- SD) in 10 type I insulin dependent diabetic patients and 96 +/- 18, 452 +/- 87, 0.21 +/- 0.02, 143 +/- 2 in five matched normal subjects, respectively. The lithium and sodium clearances were significantly lower in diabetic patients than in normal subjects (23 +/- 5 ml min-1 1.73 m-2 vs 28 +/- 6, p less than 0.05 and 1.1 +/- 0.4 vs 1.6 +/- 0.3, p less than 0.01 respectively). The fractional lithium reabsorption was greater (0.77 +/- 0.04 vs 0.72 +/- 0.03, p less than 0.05) and the distal fractional sodium reabsorption smaller (0.22 +/- 0.04 vs 0.27 +/- 0.03, p less than 0.01) in the diabetic patients compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tubular Na+ handling in type I insulin-dependent diabetics during saline and ketone body infusion. 269 81

The inadequate insulin secretory response to glucose stimulation in non-insulin dependent diabetes has been attributed to many factors including high PGE2 levels blunting the secretory response, and to the existence of inhibitory opiate activity in vivo. The purpose of the present work was to see if there was a connection between these two independent theories. Radioimmunoassayable PGE2 in islets of Langerhans was found to be proportional to islet number and protein content and was typically 4 to 5pg/micrograms islet protein. Indomethacin (2.8 X 10(-5) M), sodium salicylate (1.25 X 10(-3) M) and chlorpropamide (7.2 X 10(-5) M) all lowered islet PGE2 levels and stimulated insulin release in vitro. Dynorphin (1-13), stimulated insulin release at a concentration of 6 X 10(-9) M, while lowering islet PGE2. Conversely, at a higher concentration, (6 X 10(-7) M), dynorphin had no stimulatory effect on insulin secretion and did not lower PGE2 levels in islets or in the incubation media. The stimulatory effects of dynorphin and sodium salicylate on insulin secretion were blocked by exogenous PGE2 (10(-5) M). PGE2 at a lower concentration (10(-9) M) did not exert any inhibitory effect on dynorphin- or sodium salicylate-induced insulin release. This concentration of exogenous PGE2 stimulated insulin release in the presence of 6mM glucose. Results from these experiments suggest that since an opioid peptide can lower endogenous PGE2 production in islets and since the stimulatory effects of the opioid peptide are reversed by exogenous PGE2 there may be interactions between these two modulators of insulin secretion.
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PMID:Opiate-prostaglandin interactions in the regulation of insulin secretion from rat islets of Langerhans in vitro. 289 15

The urinary extraction of albumin, retinol binding protein, and N-acetyl-beta-D-glucosaminidase were studied in 60 children with insulin dependent diabetes mellitus and in 45 normal children to find out whether the renal tubules played a part in causing the early increase in urinary excretion of albumin that occurs in diabetes mellitus. Two overnight urine samples were collected and the protein excretion measured and expressed as the geometric mean of the protein to creatinine ratio (urinary albumin:creatinine ratio, urinary retinol binding protein:creatinine ratio, and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio, respectively). The excretion of all three proteins was significantly higher in the diabetic children with 15 (25%) of urinary albumin:creatinine ratio, 16 (27%) of urinary retinol binding protein:creatinine ratio, and 43 (72%) of urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio values being above the normal range. Significant correlations were observed between urinary albumin:creatinine ratio and urinary retinol binding protein:creatinine ratio, urinary albumin:creatinine ratio and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio, and urinary retinol binding protein:creatinine ratio and urinary N-acetyl-beta-D-glucosaminidase:creatinine ratio. There were also significant correlations between glycated haemoglobin 1c (HbA1c) and these proteins, especially N-acetyl-beta-D-glucosaminidase. No correlations were observed with the fractional excretion of sodium, flow rate of urine, glomerular filtration rate, or blood pressure. These data show that tubular abnormalities are present early in the course of insulin dependent diabetes mellitus and suggest that the early increase in urinary excretion of albumin may be at least partly tubular in origin, and that glycaemic control may influence this aspect of proximal tubular function.
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PMID:Renal tubular proteinuria and microalbuminuria in diabetic patients. 292 63

One hundred and twenty-eight surgical operations in diabetic patients have been studied to assess the effectiveness, under routine clinical conditions, of a management regimen based on the use of glucose-insulin-potassium infusion (GIK). Forty-four non-insulin-dependent diabetic (NIDDM) and 41 insulin-dependent diabetic (IDDM) patients received GIK. Mean blood glucose on the day of operation was 9.3 +/- S.D. 2.2 mmol/l in NIDDM and 8.9 +/- 2.3 mmol/l in IDDM patients. Acceptable control on the day of operation (defined as mean blood glucose 5-12 mmol/l without hypoglycaemia) was achieved in 70 (82%) patients. Eleven of 15 failures were attributable to incorrect implementation of the protocol. Though 10 units Soluble insulin/500 ml 10% glucose (0.32 units/g glucose) was needed in 61% of patients, 26% required a higher and 13% a lower dose. Plasma potassium concentration did not change after 24 h of GIK infusion, but sodium concentration fell (136 +/- 5 to 132 +/- 5 mmol/l; p less than 0.01), with 12 of 32 patients having post-operative values less than 130 mmol/l. Forty-three NIDDM patients undergoing minor surgery were managed without insulin, and acceptable control was achieved in 40 (93%). We conclude that the regimen described is a satisfactory routine means of managing diabetes during surgery, but that optimal results depend on careful monitoring with appropriate alteration of therapy.
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PMID:Management of diabetes during surgery with glucose-insulin-potassium infusion. 295 Nov 40

Potential impairment of the efficacy of human atrial natriuretic peptide (human ANF-(99-126), hANP), the most potent endogenous natriuretic agent in healthy subjects, was examined in eight male normotensive patients with uncomplicated type 1 diabetes mellitus (aged 22-37 years). After giving informed consent, patients and eight male control subjects (aged 22-28 years) received in a random double-blind study design i.v. bolus injections of 100 micrograms hANP (Bissendorf peptide) or placebo. At base-line, patients differed from controls in elevated creatinine clearance (P less than 0.05) and in mild postprandial hyperglycemia. Whereas the responses of urinary cyclic guanosine monophosphate, the second messenger of hANP, were found to be normal in patients, the diuretic and natriuretic effects of hANP were grossly impaired when compared to controls (P less than 0.01); hANP resulted in increased plasma protein concentrations only in controls (P less than 0.05 vs patients). In both groups, creatinine clearance remained uninfluenced by hANP. There were similar decreases in plasma renin activity, aldosterone, levels, and blood pressure (systolic more than diastolic) in both groups (P less than 0.05 vs placebo). Heart rate and blood glucose remained unchanged. Thus, there is evidence for a decreased responsiveness to hANP exclusively of renal fluid, sodium, and chloride excretion in uncomplicated type 1 diabetes mellitus. The mechanisms responsible for this phenomenon remain obscure, neither a down regulation at the hANP receptor sites nor an hANP-induced shift from intra- to extravascular fluid volume are likely to be involved in its probably diabetes-specific pathogenesis.
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PMID:Impaired renal responsiveness to human atrial natriuretic peptide (hANP) in normotensive patients with type 1 diabetes mellitus. 297 Nov 31

In order to evaluate the influence of the GABAergic system in the regulation of PRL secretion in patients with IDDM, serum PRL levels were measured in 7 diabetics and in 7 normal men with sodium valproate (400 mg per os), a drug capable of increasing cerebral GABA concentrations. A significant decrease of serum PRL concentrations was observed between 30 and 120 min after sodium valproate administration in both control and diabetic subjects. The time course and magnitude of the sodium valproate effect were similar in all subjects. These data confirm the inhibitory control of the GABAergic system on PRL secretion in man as evidenced by the GABAergic drug sodium valproate. It is suggested that this system is not altered in diabetic patients.
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PMID:The GABAergic control of prolactin release is not affected by insulin-dependent diabetes mellitus: evidence from studies with sodium valproate. 301 24

Excretion of digoxin-like immunoreactivity (DLIS) was measured by RIA in timed overnight urine collections from 91 normotensive nondiabetic subjects and 104 normotensive insulin-dependent diabetic (IDDM) patients. The mean +/- SD DLIS excretion rate for the diabetic patients significantly exceeded that for the controls (73 +/- 41 vs 63 +/- 36 pg/min, P = 0.024). In both groups, the mean DLIS excretion rates for men were significantly higher (P = 0.0014, P = 0.006) than for women. In the controls, the DLIS excretion rate significantly correlated with the urinary excretion rate of creatinine (P less than 0.01), Na+ (P less than 0.05), and K+(P less than 0.05), and with the subjects' body weight (P less than 0.01), body mass index (P less than 0.05), and systolic blood pressure (P less than 0.05). In the diabetics, the DLIS excretion rate was significantly correlated with body weight (P less than 0.05) and with urinary excretion rates for albumin (P less than 0.01), creatinine (P less than 0.01), Na+ (P less than 0.05), and K+(P less than 0.05). Our data indicate that: (a) increased amounts of a cardiac glycoside-like substance (or a group of substances) are excreted in the urine of IDDM patients; (b) the urinary excretion of DLIS seems to depend on glomerular filtration rate and physiocochemical properties of glomerular membrane, as well as on subjects' body mass; and (c) because cardiac glycoside-like substances may increase peripheral vascular resistance, increased urinary excretion of DLIS by IDDM patients may indicate a tendency to develop hypertension.
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PMID:Increased urinary excretion of digoxin-like immunoreactive substance by insulin-dependent diabetic patients: a linkage with hypertension? 319 78

Stiff-man syndrome is a rare disorder of the central nervous system consisting of progressive, fluctuating muscle rigidity with painful spasms. It is occasionally associated with endocrine disorders, including insulin-dependent diabetes, and with epilepsy. We investigated the possible existence of autoimmunity against the nervous system in a patient with stiff-man syndrome associated with epilepsy and Type I diabetes mellitus. Levels of IgG, which had an oligoclonal pattern, were elevated in the cerebrospinal fluid. The serum and the cerebrospinal fluid produced an identical, intense staining of all gray-matter regions when used to stain brain sections according to an indirect light-microscopical immunocytochemical procedure. The staining patterns were identical to those produced by antibodies to glutamic acid decarboxylase (the enzyme responsible for the synthesis of gamma-aminobutyric acid). A band comigrating with glutamic acid decarboxylase in sodium dodecyl sulfate-polyacrylamide gels appeared to be the only nervous-tissue antigen recognized by cerebrospinal fluid antibodies, and the predominant antigen recognized by serum antibodies. These findings support the idea that an impairment of neuronal pathways that operate through gamma-aminobutyric acid is involved in the pathogenesis of stiff-man syndrome, and they raise the possibility of an autoimmune pathogenesis.
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PMID:Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type I diabetes mellitus. 328 Oct 11

Altered sorbitol and myo-inositol metabolism, (Na,K)-ATPase function, electrochemical sodium gradients, axonal swelling, and distortion and disruption of the node of Ranvier ("axo-glial dysjunction") directly implicate hyperglycemia in the pathogenesis of neuropathy in diabetic rats, but the relevance of this sequence to clinical neuropathy in heterogeneous groups of diabetic patients remains to be established. Fascicular sural nerve morphometry in 11 patients with neuropathy complicating insulin-dependent diabetes revealed a pattern of interrelated structural changes strikingly similar to that of the diabetic rat when compared to age-matched controls. 17 older non-insulin-dependent diabetic patients with comparable duration and severity of hyperglycemia and severity of neuropathy, displayed similar nerve fiber loss, paranodal demyelination, paranodal remyelination and segmental demyelination compared to age-matched controls, but axo-glial dysjunction was replaced by Wallerian degeneration as the primary manifestation of fiber damage, and fiber loss occurred in a spatial pattern consistent with an ischemic component. The mechanistic model developed from the diabetic rat does indeed appear to apply to human diabetic neuropathy, but superimposed hormonal, metabolic, vascular, and/or age-related effects alter the morphologic expression of the neuropathy in non-insulin dependent diabetes.
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PMID:Histopathological heterogeneity of neuropathy in insulin-dependent and non-insulin-dependent diabetes, and demonstration of axo-glial dysjunction in human diabetic neuropathy. 333 24


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