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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Norepinephrine was infused for 60 minutes in high physiological concentration (0.08 microgram/kg/min) into seven insulin dependent diabetic subjects with no demonstrable endogenous insulin secretion and into seven normal subjects. Insulin dependent diabetic subjects had a stable, free insulin concentration of 23 +/- 5 microunits/ml which was unaffected by norepinephrine infusion. In the normal subjects, norepinephrine induced an initial inhibition of insulin secretion which lasted for approximately 20 minutes. Norepinephrine infusion caused a rapid increase in both ketone body and glucose concentrations but this response did not differ between the two groups. In contrast, plasma nonesterified fatty acid and triglyceride concentrations were increased significantly more in the normal than in the diabetic subjects. The increase in plasma glucagon concentrations was similar in the two groups of subjects. The cause of the differential metabolic response to norepinephrine between the normal and diabetic groups was not resolved, but may be related, at least in part, to suppression of endogenous insulin secretion in the normal subjects.
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PMID:The metabolic response to norepinephrine in normal versus diabetic man. 72 Jul 76

We studied 14 patients (11 women and 3 men) from 18 to 33 years old, suffering from type I diabetes mellitus with normal renal function (creatinine clearance 106.91 +/- 28.73 ml/min) and serum uric acid below 2.5 mg/dl (2.34 +/- 0.11 mg/dl) as well as a high uric acid clearance (23.04 +/- 5.92 ml/min) and fractional urate excretion (21.4 +/- 2.6) versus urate clearance 9.82 ml/min and fractional urate excretion 8.80 +/- 1.3 in 14 normal control subjects. The study of the uricosuric mechanisms was conducted by the combination of probenecid (PB) test which inhibits the reabsorption of secreted urate, and pyrazinamide (PZA) test, which inhibits its tubular secretion. The results of studies indicate that the increase in urate clearance was accounted for by increased PZA-nonsuppressible urate suggesting a decreased reabsorption of filtered urate. Increased PZA-suppressible urate excretion combined with impaired response to a uricosuric drug is consistent with impaired reabsorption of secreted urate. According to our findings, increased urate excretion in diabetic patients may be attributed to the inhibition of both filtered and secreted reabsorption. This reabsorptive tubular abnormality is consistent with the view of an interference of tubular reabsorption of glucose with the tubular capacity for uric acid reabsorption.
Nephron 1991
PMID:Insulin-dependent diabetes and renal hypouricemia. 194 43

Nephron loss is a common progression of a diverse range of kidney diseases. Recent experimental models of chronic renal disease have suggested that hemodynamic and nonhemodynamic mechanisms play key roles in progressive renal injury. Extensive renal ablation in the rat was followed by development of altered glomerular hemodynamics. Albuminuria and histologic damage leading to focal glomerulosclerosis were preceded by the development of increased glomerular pressures and were prevented by interventions such as severe dietary protein restriction and angiotensin-converting enzyme (ACE) inhibitor therapy. Both experimental interventions ameliorated glomerular hypertension. It was therefore concluded that these interventions ameliorated injury by glomerular hemodynamic effect. Similar findings were obtained in a rat model of type I diabetes mellitus induced by streptozotocin in which glomerular hemodynamic factors appeared important to the development of progressive renal disease. Recent studies have suggested that nonhemodynamic factors have important roles in the progression of glomerular injury. For example, although the predominant effects of ACE inhibitor therapy appear to be hemodynamically mediated, data are emerging which suggest that these agents may also influence growth/proliferation of glomerular cells. Because hyperplasia/hypertrophy may influence glomerular susceptibility to injury, this may also be a potential mechanism whereby ACE inhibitor therapy influences glomerular damage. In addition, a variety of studies have suggested that hyperlipidemia, which is frequent accompaniment of glomerular disease, is an important modulator of glomerular injury independent of glomerular hemodynamic effects. Coagulation factors, calcium phosphorus balance, as well as the genetic susceptibility of the glomerulus to injury, all appear to contribute to progressive nephron destruction.
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PMID:Renal protective effects of angiotensin-converting enzyme inhibition. 218 11

Insulin-dependent diabetes mellitus (IDDM) in humans is accompanied by an attenuation of the response of glucagon to hypoglycemia. To identify an animal model of IDDM with alpha-cell unresponsiveness to glucopenia in which to pursue morphologic and in vitro functional investigation of the lesion, pancreases isolated from rats with IDDM induced by streptozocin (STZ) or occurring spontaneously in BB/W rats were perfused with buffer containing 150, 25, and 150 mg/dl of glucose. In both forms of IDDM the normal glucagon rise during glucopenia was markedly impaired, suggesting an abnormality comparable to that of human IDDM. Studies of the insular sympathetic apparatus were conducted in these rat models. Electron-microscopic examination of peri-insular nerve endings disclosed no discernible abnormality in either form of rat IDDM. However, morphometric analysis of contacts between [3H]norepinephrine-labeled sympathetic nerve terminals and alpha-cells in pancreases from STZ-induced diabetic (STZ-D) rats revealed a 65-70% reduction in direct contacts. An 80% reduction in the number of nerve endings (not labeled) in direct contact with alpha-cells was also noted in the BB/W diabetic rats. Norepinephrine reuptake, studied only in the STZ-D group, was not impaired. The availability of local endogenous norepinephrine to alpha-cells and their sensitivity to exogenous norepinephrine was determined by perfusing 2, 5, or 10 micrograms/ml of tyramine, a releaser of endogenous norepinephrine, and norepinephrine at a concentration that in pancreases from nondiabetic rats gave a quantitatively similar glucagon response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphologic and functional changes in sympathetic nerve relationships with pancreatic alpha-cells after destruction of beta-cells in rats. 354 58

A modified M-mode ultrasound echo system had been employed to study blood-vessel geometry of the intact femoral artery before and after Norepinephrine (NE) infusion. 14 patients with juvenile IDDM aged below 35 years and 11 healthy subjects participated in the study. In the diabetic group, wall distensibility (delta D/delta P) was reduced (p less than 0.01) at control conditions. After NE infusion, wall distensibility decreased in both groups (p less than 0.01). The decrease of wall distensibility is due to an increase in pulse pressure (delta P) (p less than 0.002) in the diabetic group and a reduction of pulsatile diameter (delta D) (p less than 0.02) in the normal group. Increased stiffening of the arteriaL wall after NE infusion with progressive reduction of wall strain (delta D/Dd) is the typical finding in the normal group. No change of wall strain was observed in the diabetic group. The functional alteration of the diabetic femoral artery may be described as diminished resistance of the arterial wall to the distending force of rising blood pressure.
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PMID:Influence of norepinephrine on vessel geometry of the intact femoral artery in juvenile insulin-dependent diabetics-evidence of early diabetic angiopathy in central arteries. 703 61

The effects of acute deprivation of insulin on renal glomerular and tubular functions were studied in 10 children with juvenile diabetes mellitus. Serum glucose concentrations were similar when insulin was administered (251 +/- 112 mg/dl) and when it was withheld (306 +/- 130 mg/dl; 0.5 greater than 0.2). Acute insulin deprivation was associated with a significant reduction in glomerular filtration rate, from 151 +/- 48 ml/min/1.73 m2 to 114 +/- 41 ml/min/1.73 m2 (p less than 0.01). The fractional excretion of sodium rose from 0.45 +/- 0.43 to 0.85 +/- 0.54% (p less than 0.05) and was associated with an enhanced natriuresis; the urinary excretion of sodium increased from 1.67 +/- 1.23 to 2.43 +/- 1.72 microEq/min/kg body weight (p less than 0.05), whereas the urinary excretion of phosphate was not significantly altered from control values. During insulin deprivation a drop occurred in the serum concentration of calcium from 10.37 +/- 0.52 to 9.73 +/- 0.61 mg/dl (p less than 0.01) as well as in its urinary excretion from 0.34 +/- 0.24 to 0.24 +/- 0.20 microgram/min/kg body weight (p less than 0.01). The serum concentration of potassium rose from 4.44 +/- 0.41 to 4.96 +/- 0.51 mEq/l, but its urinary excretion was not significantly different from control values. These data suggest that in juvenile diabetes mellitus the acute deprivation of insulin, dissociated from fluctuations in serum glucose concentration, is associated with a fall in glomerular filtration rate, an increased natriuresis, and a modified calcium and potassium homeostasis.
Nephron 1982
PMID:Renal glomerular and tubular function following acute insulin deprivation in juvenile diabetes mellitus. 705 Jul 53

Signs of glomerular, proximal and distal tubular dysfunction as well as metabolic control were studied in type 1 diabetes mellitus. To that end, the urinary excretion rates of albumin, sodium, phosphate and Tamm-Horsfall protein as well as HbA1c levels were measured in 20 patients with different degrees of diabetic nephropathy (positive Albustix for several years). Eight diabetic patients with short duration of diabetes and without any diabetic complications and 10 apparently healthy subjects were studied for comparison. The HbA1c levels in the three groups were 8.6 +/- 1.2, 5.9 +/- 2.2 and 4.1 +/- 0.4%, respectively (mean +/- SD). Duration of diabetes in the two diabetic groups were 27 +/- 7 and 3 +/- 1 years, respectively. The urinary protein levels were measured by enzyme-linked immunoassays. The fractional clearance of sodium (1.9 +/- 1.9%; p < 0.001) and phosphate (27 +/- 11%; p < 0.01) were increased in patients with diabetic nephropathy compared to diabetic patients without nephropathy (0.6 +/- 0.2 and 16 +/- 4%) and healthy control subjects (0.6 +/- 0.1 and 16 +/- 4%, respectively). Tamm-Horsfall protein excretion rate was decreased in both diabetic groups (15.0x/3.1 and 37.9x/1.9 micrograms/min, geometric mean x/tolerance factor, p < 0.001 and p < 0.05, respectively) compared to the healthy subjects (63.8x/1.3 micrograms/min). Furthermore, patients with diabetic nephropathy had a lower excretion rate of Tamm-Horsfall protein (15.0x/3.1 micrograms/min) compared to patients without signs of nephropathy (37.9x/1.9 micrograms/min, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Nephron 1993
PMID:Tubular secretion of Tamm-Horsfall protein is decreased in type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. 824 85

The aim of this study was to assess the relationship between markers of tubular function, markers of glycaemic control and erythrocyte sodium-lithium countertransport activity (SLC) in 40 normotensive, normoalbuminuric insulin-dependent diabetic (IDDM) subjects and 11 normal control subjects. Nine IDDM subjects had SLC > 0.40 mmol lithium h-1 litre RBC-1. Glomerular filtration rate (GFR) and the excretion rate of retinol-binding protein (RBP), N-acetyl-beta-D-glucosaminidase (beta-NAG) and glucose were significantly higher in IDDM subjects compared to control subjects (Mann-Whitney test, p = 0.02, < 0.001, < 0.001 and < 0.001, respectively), whilst the two groups had similar SLC and TmPO4 levels. There was no significant relationship between SLC and the other variables in IDDM subjects, even when comparing IDDM subjects with normal and high SLC. beta-NAG excretion rate was correlated to urinary glucose (rs 0.47, p = 0.001) and, weakly, to the other markers of glycaemic control (fasting blood glucose rs = 0.31, p = 0.03, fructosamine rs 0.28, p = 0.04, HbA1 rs 0.27, p = 0.04). RBP excretion rate was correlated to the excretion rate of beta-NAG (rs 0.38; p = 0.007) and albumin (rs 0.45; p = 0.002); the excretion rates of beta-NAG and albumin were significantly associated (rs 0.37, p = 0.009). Diabetes duration did not correlate to any of the aforementioned variables. In this study, beta-NAG and RBP overnight excretion rates were higher in normoalbuminuric IDDM subjects compared to control subjects but no relationship was present between SLC and tubular function in IDDM patients without complications. Excretion rates of different proteins appear to be interrelated and, in IDDM, beta-NAG excretion is associated with glycaemic control.
Nephron 1996
PMID:Measures of tubular function in normoalbuminuric insulin-dependent diabetic patients and their relationship with sodium lithium countertransport activity. 885 60

Insulin-dependent diabetes mellitus (IDDM) patients may have an increased intrarenal angiotensin II activity. In diabetic patients, captopril increases the renal hemodynamic response to an amino acid infusion. We investigated the effects of two salt diets on arterial pressure and renal response to a protein load in 10 normotensive (blood pressure < 140/90 mm Hg) IDDM patients (aged 30 +/- 3 years) who had diabetes for 7 +/- 4 years and normoalbuminuria levels [albumin excretion rate 4.8 (2.5-19.1) microg/min]. After 1 week of normal (approximately 100 mmol/day; approximately 100 mEq/l) and 1 week of high (approximately 300 mmol/day; approximately 300 mEq/l) salt intake, renal hemodynamic studies were performed at baseline and after a protein load (meat meal) of 100 g/1.73 m2. The mean 24-hour urinary sodium excretion levels were 99 +/- 27 and 293 +/- 80 mmol (mEq) with normal and high salt intake, respectively. No significant changes were seen in plasma sodium and glucose control with the normal and high salt diets, respectively: plasma sodium 135 +/- 3 vs. 137 +/- 1 mmol/l (mEq/l), (p = 0.08) and glycated hemoglobin 9.1 +/- 1.9 vs. 9.4 +/- 2.1% (p = 0.36). The body weight (70.9 +/- 12 vs. 71.8 +/- 13 kg; p = 0.015) was significantly higher with a high salt diet. The mean arterial pressure was similar with both diets (normal vs. high salt diet 91 +/- 9 vs. 89 +/- 6 mm Hg, p = 0.25). The plasma renin concentration [28 +/- 15 vs. 16 +/- 6 microU/ml(168 +/- 90 vs. 96 +/- 36 pmol/l), p = 0.013] and angiotensin II [8.8 +/- 4.4 vs. 6.4 +/- 3.5 pg/ml (0.052 +/- 0.025 vs. 0.038 +/- 0.021 nmol/l), p = 0.016] were significantly lower with the high salt diet. Following protein loading, the glomerular filtration rate increased with both diets: normal salt diet 114 +/- 26 vs. 128 +/- 30 ml/min/1.73 m2(1.9 +/- 0.43 vs. 2.13 +/- 0.50 ml/s/1.73 m2), p = 0.04; high salt diet 118 +/- 23 vs. 127 +/- 29 ml/min/1.73 m2 (1.97 +/- 0.38 vs. 2.12 +/- 0.48 ml/s/1.73 m2), p = 0.13. The change in renal plasma flow was similar to that of the glomerular filtration rate with normal and high salt intake, respectively: 566 +/- 94 vs. 617 +/- 142 ml/min/1.73 m2 (9.44 +/- 1.57 vs. 10.29 +/- 2.37 ml/s/173 m2), p = 0.0017; 572 +/- 125 vs. 600 +/- 110 ml/min/1.73 m2 (9.54 +/- 2.08 vs. 10.00 +/- 1.83 ml/s/1.73 m2), p = 0.057. In this subset of normotensive normoalbuminuric IDDM patients, a high salt intake did not promote an exaggerated renal response to the protein load despite inhibition of the renin-angiotensin system.
Nephron 1997
PMID:Renal functional response to protein loading in type 1 (insulin-dependent) diabetic patients on normal or high salt intake. 927 38

Type 1 diabetes mellitus results from an autoimmune destruction of pancreatic beta-cells. Cytokines, such as interleukin-1 beta and interferon-gamma, are putative mediators of immune-induced beta-cell death and, under in vitro conditions, cause beta-cell apoptosis. We have recently shown that interleukin-1 beta + interferon-gamma modifies the expression of >200 genes in beta-cells. Several of these genes are putative targets for the transcription factor nuclear factor-kappa B (NF-kappa B), and in subsequent experiments we showed that NF-kappa B activation is mostly pro-apoptotic in beta-cells. To identify cytokine-induced and NF-kappa B-regulated genes in primary rat beta-cells, we presently combined two experimental approaches: 1) blocking of NF-kappa B activation in cytokine-exposed beta-cells by a recombinant adenovirus (AdI kappa B((SA)2)) containing an inhibitor of NF-kappa B alpha (I kappa Bac) super-repressor (S32A/S36A) and 2) study of gene expression by microarray analysis. We identified 66 cytokine-modified and NF-kappa B-regulated genes in beta-cells. Cytokine-induced NF-kappa B activation decreased Pdx-1 and increased c-Myc expression. This, together with NF-kappa B-dependent inhibition of Glut-2, pro-hormone convertase-1, and Isl-1 expression, probably contributes to the loss of differentiated beta-cell functions. NF-kappa B also regulates several genes encoding for chemokines and cytokines in beta-cells. The present data suggest that NF-kappa B is a key "switch regulator" of transcription factors and gene networks controlling cytokine-induced beta-cell dysfunction and death.
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PMID:A comprehensive analysis of cytokine-induced and nuclear factor-kappa B-dependent genes in primary rat pancreatic beta-cells. 1168 80


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