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)

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.
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PMID:Renal glomerular and tubular function following acute insulin deprivation in juvenile diabetes mellitus. 705 Jul 53

Amylin is normally secreted in a regulated fashion by the pancreatic beta-cells in parallel with insulin and has been reported to have bone-conserving properties. Type I diabetes mellitus results in a low-turnover osteopenia in the presence of decreased amylin, which is in contrast to type II diabetes where less bone loss, in the presence of high amylin levels, occurs. We investigated the effects of amylin on bone mineral metabolism in normal and diabetic (streptozotocin-induced) rats, in order to ascertain whether amylin would modify the streptozotocin-induced diabetic osteopenia. Ten-week-old male Sprague-Dawley rats were randomized as follows: group A (n = 18) received normal saline; group B (n = 18) received amylin; group C, diabetic rats (n = 23), received normal saline; and group D, diabetic rats (n = 23), received amylin. Amylin (100 pmol/100 g b.w.) was administered by a daily subcutaneous injection. Double calcein-labeled tibiae were removed for histomorphometric analysis followed sacrifice on day 19. Results showed no difference in blood ionized calcium between groups. Blood glucose remained above 600 mg/dl in the diabetic animals and was not affected by the administration of amylin. Serum osteocalcin, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), and 1,25 dihydroxyvitamin D [1,25(OH)2D] were significantly lower in the diabetic rats compared with control group A by day 19. Amylin produced higher levels of serum osteocalcin in group B on day 9 (P < 0.05) compared with controls but returned to control values (group A) by day 19; no such change occurred in the diabetic group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amylin increases bone volume but cannot ameliorate diabetic osteopenia. 779 48

A case of an 18-year-old female with polyglandular autoimmune syndrome (PGA) type 1 complicated by slowly progressive IDDM was described. She had epilepsy at the age of 5, and mucocutaneous candidiasis and hypoparathyroidism at 7 years. At the age of 18, the patient noticed thirst and body weight loss. On admission, she had uneven teeth and chronic mucocutaneous candidiasis. Plasma blood glucose was 312 mg/dl without ketosis, hemoglobin Alc 9.1%, serum calcium 3.5 mEq/l, serum phosphorus 6.0 mg/dl. A CT scan of her brain revealed calcification in the bilateral basal ganglia. Serum intact PTH was less than 10 pg/ml. Ellsworth-Howard's test showed hyperresponsiveness in the secretion of urinary phosphorus and cyclic-AMP. Other endocrinological studies showed no abnormality except for mild hyporesponsiveness in the secretion of urinary C-peptide (39.6 mu g/day). After admission, she was initially treated with diet alone with positive islet cell antibody (ICA). Three months later she was treated with low dose insulin, and ICA became negative. Then 5 months later it became positive again. Sixteen months later she had IDDM with positive ICA and without the secretion of urinary C-peptide. On the basis of these results, we diagnosed this case as PGA type 1 with the manifestations of hypoparathyroidism, chronic mucocutaneous candidiasis and slowly progressive IDDM. This is the second case report in Japan about PGA type 1. Furthermore, this case demonstrates for the first time in Japan that slowly progressive IDDM is complicated by PGA type 1. The patient had this HLA typing: A 24(9), BW52(5), BW60(40), CW3, DR2, DRW12, DQW7. More investigation is necessary to clarify the mechanism of PGA type 1.
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PMID:[A case of polyglandular autoimmune syndrome (PGA) type 1 complicated with slowly progressive IDDM]. 789 66

To investigate the function of HLA-class II genes in the autoimmune response of insulin dependent diabetes mellitus (IDDM), the HLA-class II gene of IDDM patients was introduced into Ltk- cells with pSV2-neo plasmid, using the calcium phosphate precipitation technique. We obtained a stable cell line expressing the HLA-class II gene from lymphocytes of IDDM patients. Expression was identified by direct ox erythrocyte-CrCl3-HLA DR monoclonal antibody rosetting.
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PMID:Expression of HLA-class II genes of IDDM patients on the surface of the LTK- cells. 800 56

Animal studies on the progression of chronic renal disease have limited applicability to humans. However, human kidneys also progressively deteriorate once they have suffered a certain degree of initial damage. Various therapeutic approaches to slowdown the progression of chronic renal disease [low-protein diets, angiotensin converting enzyme (ACE) inhibitors, etc.] seem promising. Large-scale, ongoing clinical studies may offer definitive answers to their place in the management of progressive renal disease. Diabetic nephropathy, the most common cause of end-stage renal failure, follows a distinct course in insulin dependent diabetes mellitus DM (IDDM); this is less well defined in non-insulin dependent DM (NIDDM). Micro-albuminuria is an important hallmark of early diabetic kidney disease, when it may still be amenable to therapeutic interventions. Strict glycemic control, and ACE inhibitors may be beneficial in early stages of diabetic nephropathy. Less is known on use of calcium-channel blockers and low-protein diets in diabetic nephropathy. There is also a paucity of information on management of diabetic nephropathy in type II DM.
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PMID:Progression of chronic renal disease and diabetic nephropathy: a review of clinical studies and current therapy. 825 40

Glomerular vasodilatation in the early stages of type I diabetes mellitus apparently results from arteriolar insensitivity to vasoconstrictors. Since cytosolic free calcium ([Ca2+]i) is a major signaling mechanism for smooth muscle contraction, we studied whether growth of smooth muscle-like rat glomerular mesangial cells in media with high glucose concentration affects [Ca2+]i responses to vasoconstrictors. In cells grown for five days in 22 mM glucose, we observed blunted responsiveness to three structurally unrelated vasoconstrictors that elevate [Ca2+]i via a phospholipase C-dependent mechanism, angiotensin II, prostaglandin F2 alpha, and arginine vasopressin. Inhibition of [Ca2+]i responses was not due to an osmotic effect of high glucose, since it was not mimicked by hypertonic mannitol. While the size of intracellular Ca2+ pools was unaffected by elevated glucose, Na+/Ca2+ exchange was markedly inhibited, thus ruling out both impaired filling of Ca2+ stores and enhanced counter-regulatory mechanisms. Impaired myoinositol transport or intracellular sorbitol accumulation were not responsible for the effects of high glucose, since supplementation of media with myo-inositol or with the aldose reductase inhibitor. Alcon 1576, failed to reverse insensitivity to vasoconstrictors. On the other hand, down-regulation or pharmacological inhibition of protein kinase C completely reversed the effects of high glucose, thus indicating involvement of this signal transduction pathway. These data suggest a possible intracellular mechanism for the impaired vascular sensitivity underlying early renal hemodynamic changes in diabetes mellitus.
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PMID:High glucose inhibits cytosolic calcium signaling in cultured rat mesangial cells. 845 57

Serum osteocalcin levels are a marker of bone formation. In this study, bone and mineral metabolism in type I diabetes mellitus (DM) were investigated, and the changes related to diabetic microvascular complications were examined. Serum calcium (Ca), inorganic phosphate (P), osteocalcin (OC) and parathyroid hormone (PTH) levels were measured in 42 type I diabetic subjects. Diabetics were subdivided into those with or without complications. Age and sex-matched control subjects were used for comparisons with the diabetic groups. Serum P and PTH levels were not different from those of controls. Serum Ca levels were significantly increased (p < 0.001) although the values were within the normal range. OC levels were significantly lower in the complicated (retinopathy and/or protenuria) diabetic group (p < 0.005). In Type I diabetes mellitus, the serum OC level is influenced by the presence of microvascular complications.
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PMID:Serum osteocalcin levels in type I diabetes mellitus. 856 May 99

The establishment of gene delivery systems that result in efficient transfection of the pancreatic beta-cells may generate an important tool for the study of IDDM and may also represent one critical step toward a clinical application of gene transfer for the prevention or early treatment of the disease. Using the reporter gene vectors pCAT and pCMV beta-gal, we have investigated the efficiency of transfection mediated by calcium phosphate precipitation, the monocationic liposome Lipofectin, the polycationic liposome Lipofectamine, and adenovirus-polylysine (AdpL) DNA complexes in human, mouse, rat, and fetal porcine islet cells. In all species studied, calcium phosphate-mediated transfection resulted in lower chloramphenicol acetyl transferase (CAT) activities than the other methods. Intact human, mouse, and rat islets were poorly transfected by Lipofectin, Lipofectamine, and AdpL. When dispersed by trypsin treatment, however, human, mouse, rat, and fetal pig islect cells were efficiently transfected by Lipofectamine. Moreover, transfection of dispersed human and mouse islet cells using AdpL, also resulted in high CAT activities. The percentage of cells staining positively for beta-galactosidase after transfection with Lipofectamine was 49% for mouse, 56% for rat, and 57% for dispersed human islet cells. Transfection of human islet cells using AdpL, however, yielded 70% beta-gal-positive cells. Fluorescence-activated cell sorting-purified rat islet alpha- and beta-cells were transfected with similar efficiency using Lipofectamine. CAT expression in human islet cells transfected with either Lipofectamine or AdpL reached a peak value after 5-7 days, followed by a gradual decline. It is concluded that transfection with AdpL or Lipofectamine are both efficient means to achieve transient expression of gene constructs in human and mouse islet cells, while for rat and fetal porcine islet cells, Lipofectamine is the most efficient of the agents investigated in this study.
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PMID:Efficient gene transfer to dispersed human pancreatic islet cells in vitro using adenovirus-polylysine/DNA complexes or polycationic liposomes. 877 22

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) versus an ACE inhibitor (lisinopril) on albuminuria, arterial blood pressure, and glomerular filtration rate (GFR) in hypertensive IDDM patients with diabetic nephropathy. We performed a 1-year, double-blind, double-dummy, randomized, controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 52 hypertensive IDDM subjects with diabetic nephropathy. Three patients dropped out, and results for the remaining 49 (25 nisoldipine, 24 lisinopril) are presented. Diuretics were required in 10 nisoldipine- and 8 lisinopril-treated patients. Every 3 months, 24-h ambulatory blood pressure (TM2420, A&D, Tokyo, Japan) and albuminuria in three 24-h samples (enzyme immunoassay) were measured; GFR (51Cr-EDTA plasma clearance) was recorded every 6 months. Mean arterial blood pressure (24 h) was reduced from (mean +/- SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P = 0.06 comparing changes in the two groups). Albuminuria was reduced 47% (95% CI 21-65) in the lisinopril group versus an increase of 11% (-3 to 27) in the nisoldipine group (P = 0.001). Fractional albumin clearance was reduced 37% (95% CI 4-59%) in the lisinopril versus an increase of 35% (8-69%) in the nisoldipine group (P < 0.01). GFR decreased from 85 +/- 5 ml x min(-1) x 1.73 m(-2) to 73 +/- 5 in the lisinopril group and from 84 +/- 6 to 80 +/- 7 in the nisoldipine group (P < 0.05). The effect of study medication on albuminuria and GFR was independent of changes in systemic blood pressure and baseline variables in multiple regression analyses. In summary, lisinopril reduced albuminuria, but also GFR, to a greater extent than did nisoldipine in hypertensive IDDM patients with diabetic nephropathy during the 1st year of treatment. Longer follow-up is required to clarify whether these drugs have different renoprotective effects.
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PMID:Differences between nisoldipine and lisinopril on glomerular filtration rates and albuminuria in hypertensive IDDM patients with diabetic nephropathy during the first year of treatment. 903 6


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