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

Insulin-dependent diabetes mellitus (IDDM) induces plasma amino acid (AA) abnormalities, including low alanine and high branched-chain (BCAA). While insulin treatment restores plasma AA pattern, proline, methionine, valine, isoleucine, and total BCAA remain elevated in skeletal muscle intracellular water. This suggests that the restoration of plasma AA concentrations is not a satisfactory index of recovered AA metabolism in IDDM.
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PMID:Plasma and skeletal muscle free amino acids in type I, insulin-treated diabetic subjects. 389 23

Insulin dependent diabetes mellitus (IDDM) is an autoimmune disease with a strong association between disease and the HLA class II region. Because abnormal antigen processing, in part characterized by altered class I processing, has been identified in patients with IDDM, the TAP (transporter associated with antigen processing) genes located in the HLA class II region make attractive candidate genes for IDDM. Five coding region variants of TAP1 were typed in a cohort of well characterized Finnish patients with diabetes (n = 119) and compared to racially marched control subjects (n = 92). We found that although no single TAP1 polymorphism was associated with IDDM, a genotypic combination of Ile/Val at codon 333 with Asp/Asp at codon 637 was found more frequently in subjects with IDDM (9.4%) compared to controls (1.2%; p = 0.025). This could not be accounted for by an association with any particular haplotype defined by class I or class II serology.
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PMID:Evaluation of TAP1 polymorphisms with insulin dependent diabetes mellitus in Finnish diabetic patients. The Childhood Diabetes in Finland (DiMe) Study Group. 912 74

Platelet levels of 19 amino acids were measured in 20 outpatients with type 1 (age [mean +/- SE], 35.5 +/- 2.0 years) and 27 with type 2 (age, 58.4 +/- 1.4 years) diabetes, and 20 young (age 33.7 +/- 1.3 years) and 20 older (age 57.4 +/- 1.5 years) healthy volunteers. Platelet levels of most amino acids tended to be lower in patients with type 1 diabetes than in healthy controls. In particular, asparagine, glycine, taurine, alanine, valine, cysteine, leucine, phenylalanine, and lysine levels, expressed as nmol/10(8) platelets, were significantly lower. Only taurine significantly decreased in patients with type 2 diabetes, whereas threonine, alanine, and isoleucine increased.
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PMID:Preliminary report: Amino acid profile in platelets of diabetic patients. 1143 75

Insulin-dependent diabetes mellitus (type-1 diabetes) is an inflammatory autoimmune disease associated with vascular permeability changes leading to many complications including nephropathy, retinopathy, hypertension, hyperalgesia and neuropathy. The bradykinin B(1) receptor was recently found to be upregulated during the development of the diabetes and to be involved in its complications. Kinins are known to be important mediators of a variety of biological effects including cardiovascular homeostasis, inflammation and nociception. In the present study, we studied the effect of the selective B(1) receptor agonist, des-Arg(9)-bradykinin, and its specific antagonists, Ac-Lys-[D-beta Nal(7), Ile(8)]des-Arg(9)-bradykinin (R-715) and Ac-Orn-[Oic(2), alphaMe Phe(5), D-beta Nal(7), Ile(8)]des-Arg(9)-bradykinin (R-954), on diabetic hyperalgesia. Diabetes was induced in male CD-1 mice by injecting a single high dose of streptozotocin (200 mg kg(-1), i.p.) and the nociception was assessed using the hot plate and the tail flick tests, 1 week following the injection of streptozotocin. Our results showed that induction of diabetes by streptozotocin provoked a marked hyperalgesia in diabetic mice expressed as about 11% decrease in hot plate reaction time and 26% decrease in tail flick reaction time. Following acute administration of R-715 (200-800 microg kg(-1), i.p.) and R-954 (50-600 microg kg(-1), i.p.), this hyperalgesic activity was blocked and the hot plate and tail flick latencies of diabetic mice returned to normal values observed in control healthy mice. In addition, the acute administration of des-Arg(9)-bradykinin (200-600 microg kg(-1), i.p.) significantly potentiated diabetes-induced hyperalgesia, an effect that was totally reversed by R-715 (1.6-2.4 mg kg(-1), i.p.) and R-954 (0.8-1.6 mg kg(-1), i.p.). These results provide a major evidence for the implication of the bradykinin B(1) receptors in the development of hyperalgesia associated with diabetes and suggest a novel approach to the treatment of this diabetic complication using the bradykinin B(1) receptor antagonists.
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PMID:Role of bradykinin B(1) receptors in diabetes-induced hyperalgesia in streptozotocin-treated mice. 1246 57

Insulin-dependent diabetes mellitus (type 1 diabetes) is an inflammatory autoimmune disease associated with vascular permeability changes leading to many complications including nephropathy, retinopathy, neuropathy, hypertension and hyperalgesia. The bradykinin B(1) receptors (BKB(1)-R) were recently found to be upregulated alongside the development of type 1 diabetes and to be involved in its complications. Kinins are important mediators of a variety of biological effects including cardiovascular homeostasis, inflammation and nociception. In the present study, we studied the effect of a selective BKB(1)-R agonist desArg(9)-BK (DBK) and two selective receptor antagonists, the R-715 (Ac-Lys-[D-beta Nal(7), Ile(8)] desArg(9)-BK) and the R-954 (Ac-Orn-[Oic(2), alphaMe Phe(5), D-beta Nal(7), Ile(8)] desArg(9)-BK) on diabetic hyperalgesia. Type 1 diabetes was induced in male CD-1 mice via a single injection of streptozotocin (STZ, 200mg/kg, i.p.), one week before the test. Nociception, a measure of hyperalgesia, was assessed using the plantar stimulation (Hargreaves) and the tail-immersion tests. The induction of type 1 diabetes provoked a significant hyperalgesic activity in diabetic mice, causing an 11% decrease in plantar stimulation reaction time and 13% decrease in tail-immersion reaction time, compared to normal mice. Following acute administration of R-715 (100-600 microg/kg, i.p.), or R-954 (50-400 microg/kg, i.p.), the STZ-induced hyperalgesic activity was blocked in a dose-dependent manner and the hot plate and tail-immersion latencies of diabetic mice returned to normal values observed in control healthy mice. In addition, the acute administration of DBK (400 microg/kg, i.p.) significantly potentiated diabetes-induced hyperalgesia, an effect that was totally reversed by R-715 (1.6-2.4 mg/kg, i.p.) and R-954 (0.8-1.2mg/kg, i.p.). These results provide further evidence for the implication of the BKB(1)-R in type 1 diabetic hyperalgesia and suggest a novel approach in the treatment of this complication using the BKB(1)-R antagonists.
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PMID:Kinin B1 receptor antagonists inhibit diabetes-induced hyperalgesia in mice. 1263 34

Altered peptide ligands derived from T cell-reactive self antigens have been shown to be protective therapeutic agents in animal models of autoimmunity. In this study we identified several altered peptide ligands derived from the type 1 diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65) epitope that were capable of antagonizing a subset of a panel of human CD4(+) GAD65 (555-567)-responsive T cell clones derived from a diabetic individual. While no altered peptide ligand was able to antagonize all six clones in the T cell panel, a single-substituted peptide of isoleucine to methionine at position 561, which resides at the TCR contact p5 position, was able to antagonize five out of the six hGAD65-responsive clones. In a mixed T cell culture system we observed that altered peptide ligand-mediated antagonism is inhibited in a dose-dependent manner by the presence of non-antagonizable hGAD65 (555-567)-responsive T cells. From an analysis of the cytokines present in the mixed T cell cultures, interleukin-2 was sufficient to inhibit altered peptide ligand-induced antagonism. The inhibition of altered peptide ligand-mediated antagonism of self-antigen-responsive T cells by non-antagonizable T cells has implications in altered peptide ligand therapy where T cell antagonism is the goal.
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PMID:Inhibition of altered peptide ligand-mediated antagonism of human GAD65-responsive CD4+ T cells by non-antagonizable T cells. 1554 75

Most studies performed to investigate the role of the inducible bradykinin B(1) receptor in the pathology and complications of type 1 diabetes have been carried out using the model of streptozotocin (STZ)-induced diabetes. The model of spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice involves a long-term inflammatory process that closely resembles the human type 1 diabetes. In the present study, we aimed at establishing the correlation between the progress of diabetic hyperalgesia and the incidence of diabetes, as a function of age, in NOD mice. We also evaluated the implication of the bradykinin B(1) receptor, a receptor up-regulated during the inflammatory progress of diabetes, in the development of diabetic hyperalgesia in NOD mice. Female NOD mice were followed up from the 4th to the 32nd week of age for the incidence of diabetes. Only NOD mice with plasma glucose concentration >20 mmol/l were considered diabetic. The nociception was assessed using the hot plate and the tail immersion pain tests and the effect of acute and chronic administration of the selective bradykinin B(1) receptor agonist, desArg(9)bradykinin and its selective antagonists, R-715 (Ac-Lys-[D-beta Nal(7), Ile(8)]desArg(9)bradykinin) and R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8)]desArg(9)bradykinin), on the development of diabetic hyperalgesia was studied. Diabetic NOD mice developed a significant time-dependent hyperalgesia, as measured in both tests, starting from the 8th week of age with the maximum effect observed over 16 to 20 weeks, whereas the incidence of diabetes in the tested NOD mice was only 40.16% at the age of 16 weeks and reached a maximum of 73.23% at the age 24 weeks. Both acute and chronic administration of desArg(9)bradykinin (400 microg/kg) markedly increased the hyperalgesic activity in diabetic NOD mice in the hot plate and tail immersion nociceptive tests. The selective bradykinin B(1) receptor antagonist R-715 (400 microg/kg) and its more potent and long acting analogue R-954 (200 microg/kg), administered in acute or chronic manner, significantly attenuated diabetic hyperalgesia in NOD mice in both thermal pain tests and restored nociceptive responses to values observed in control non-diabetic siblings. Our results bring the first evidence that the development of hyperalgesia in NOD mice, a model of spontaneous type 1 diabetes, precedes the occurrence of hyperglycemia and is mediated by the bradykinin B(1) receptor. It is suggested that bradykinin B(1) receptor antagonism could become a novel therapeutic approach to the treatment of diabetic neuropathic complications.
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PMID:Hyperalgesia in non-obese diabetic (NOD) mice: a role for the inducible bradykinin B1 receptor. 1587 25

Diabetic lipaemia, severe hypertriglyceridaemia associated with diabetic ketoacidosis, is a well recognised, but rare condition. Why this occurs in some patients and not others is unknown. We report a case of extreme lipaemia in a 20-year-old woman with type 1 diabetes who presented to hospital with diabetic ketoacidosis (DKA). At admission the patient's blood was grossly lipaemic and plasma lipid analyses showed triglyceride and cholesterol concentrations of 379 mmol/L and 52 mmol/L, respectively. She had no peripheral stigmata of chronic hyperlipidaemia and 1 year previously her plasma triglyceride and total cholesterol concentrations were 2.5 mmol/L and 4.4 mmol/L respectively. She was treated with insulin and the hypertriglyceridaemia resolved over several days. Because of the marked hypertriglyceridaemia, lipoprotein lipase (LPL) genetic testing was performed. Sequencing of the LPL gene revealed that she was heterozygous for the common S447X LPL variant and heterozygous for a novel missense mutation in exon five (I225N). Ile(225) is highly conserved among species and this mutation is predicted to impair function of the mature LPL protein. We conclude that heterozygosity for LPL mutations may predispose to transient severe hypertriglyceridaemia, when combined with insulin deficiency.
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PMID:Extreme diabetic lipaemia associated with a novel lipoprotein lipase gene mutation. 1944

Insulin-dependent diabetes mellitus (type 1 diabetes) is an inflammatory autoimmune disease associated with many complications including nephropathy, retinopathy, neuropathy and hyperalgesia. Experimental evidence has shown that the bradykinin B1 receptor (BKB1-R) is involved in the development of type 1 diabetes and found to be upregulated alongside the disease. In the present study the effects of the selective BKB1-R antagonist the R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8) ]des-Arg(9)-BK and the BKB1-R agonist des Arg(9)-BK (DBK) were studied on diabetic hyperglycemia. Diabetic type 1 was induced in C57 BL/KsJ mdb male mice by five consecutives doses of STZ (45mg/kg i.p.). A glucose tolerance test (GTT) was performed by an intraperitoneal administration of glucose, 8, 12 and 18days after the diabetes induction. The induction of type 1 diabetes provoked a significant hyperglycemia levels in diabetic mice at 12 and 18days after STZ. The administration of R-954 (400microg/kg i.p.) at 12 and 18days after STZ returned the glycemia levels of this animals to normal values. In addition the administration of DKB (300microg/kg i.p.) significantly potentiated the diabetes-induced hyperglycemia; this effect that was totally reversed by R-954. These results provide further evidence for the implication of BKB1-R in the type 1 diabetes mellitus (insulitis).
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PMID:Antidiabetic efficacy of bradykinin antagonist R-954 on glucose tolerance test in diabetic type 1 mice. 2009 93

We investigated longitudinal change in the amino acid (AA) profile in type 1 diabetes mellitus (DM) using AKITA mice, which develop DM as a result of insulin deficiency. The plasma concentrations of valine, leucine, isoleucine, as well as the total branched chain amino acids, alanine, citrulline and proline, were significantly higher in the diabetic mice. We show that the degree and timing of the changes were different among the plasma amino acid concentrations (pAAs) during the development of type 1 DM.
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PMID:Time-dependent changes in the plasma amino acid concentration in diabetes mellitus. 2163 1


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