Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies raised to a lysine solubilized peptide composed of residues 20-29 of the pancreatic islet amyloid polypeptide react selectively and specifically with this polypeptide and with islet amyloid deposits in Type 2 diabetes mellitus. These antibodies may prove useful in studies employing radioimmunoassay of body fluids and islet cell cultures in order to define if a pathogenic relationship exists between the islet amyloid polypeptide and Type 2 diabetes mellitus.
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PMID:Antibodies specific for the pancreatic islet amyloid polypeptide associated with type 2 diabetes mellitus. 264 92

Fasting plasma zinc levels were determined in 45 IDDM and in 40 NIDDM patients. Mean values were similar in both groups, but diabetic men showed a significantly higher plasma zinc (p less than 0.05) than diabetic women. In patients with diabetic nephropathy a lower zinc level was associated with decreased plasma albumin as compared to patients without complications (p less than 0.001). Neuropathy and macro-angiopathy were also associated with lower zincemia (p less than 0.05) but in the presence of normal albumin levels. In IDDM without nephropathy a significant positive correlation was found between plasma zinc and plasma glucose, albumin, branched chain amino acids and glutamine, while in NIDDM without nephropathy a significant positive correlation exists between plasma zinc and the amino acids glutamine, valine, histidine and lysine.
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PMID:Plasma zinc levels in diabetes mellitus: relation to plasma albumin and amino acids. 375 14

Non-insulin-dependent diabetes mellitus (NIDDM) has a strong genetic component and maternal factors have recently been implicated in disease inheritance. The mitochondrial myopathies are a group of diseases which often show maternal inheritance as a result of mtDNA defects; some patients have impaired glucose tolerance. Occasional families with maternally inherited diabetes and deafness associated with a deletion or point mutation of mtDNA have been reported. To assess the importance of mitochondrial gene defects in NIDDM, 150 unrelated diabetic subjects from Wales, UK and 68 unrelated patients with diabetes and at least one affected sibling from England, UK were studied. Southern blot analysis did not show any large mtDNA deletions or duplications. One patient had a mutation in the mitochondrial tRNAleu(UUR) gene at bp 3243. This mutation is commonly associated with the syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS). Study of this patient and his siblings showed a distinct form of late-onset diabetes associated with nerve deafness but no clinical features of the MELAS syndrome. No diabetic subject was shown to have the mtDNA mutation at position 8344 (tRNA(lys)) which has previously been described in the syndrome of mitochondrial encephalomyopathy and red-ragged fibres (MERRF). The role of other mitochondrial gene defects in diabetes and the pathophysiological basis of glucose intolerance in patients with the MELAS mutation requires further elucidation.
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PMID:Mitochondrial gene defects in patients with NIDDM. 926 98

In diabetic nephropathy a major current concept for pathogenesis is increased collagen accumulation in the glomerulus by increased collagen synthesis and decreased degradation. In the present study, we tested the hypothesis whether arginine is able to influence kidney lipid peroxidation, glycoxidation, collagen accumulation, glucose-mediated cross-linking, hydroxy radical attack, protein oxidation, nitric oxide formation and albuminuria in the diabetic kk mouse. Ten diabetic kk mice were given arginine 50 mg/kg body weight, 10 diabetic kk mice were not treated and used as negative controls and 10 kk mice were kept as healthy controls. Our results show that oral administration of low-dose arginine reduces kidney collagen accumulation as reflected by kidney hydroxyproline, cross-linking as reflected by pentosidine, lipid peroxidation, glycoxidation as reflected by carboxymethyl lysine, kidney weight and albuminuria in the diabetic kk mouse. Albuminuria in untreated animals was closely correlated with lipid peroxidation. Our results in the spontaneously diabetic kk mouse representing type 2 diabetes mellitus therefore confirm and extend recent findings of collagen reduction by arginine in a different animal model. The mechanism of reducing proteinuria can be assigned to the blocking of lipid peroxidation products by L-arginine.
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PMID:Arginine reduces kidney collagen accumulation, cross-linking, lipid peroxidation, glycoxidation, kidney weight and albuminuria in the diabetic kk mouse. 904 44

Insulin lispro, a recombinant insulin analogue, is identical to human insulin except for the transposition of proline and lysine at positions 28 and 29 in the C-terminus of the B chain. The resultant reduced capacity for self-association in solution translates into more rapid absorption of insulin lispro than human regular insulin from subcutaneous sites. Maximum insulin concentrations are higher and are reached earlier with insulin lispro than with human regular insulin, and insulin concentrations return to baseline values more quickly with insulin lispro; consequently, insulin lispro has a more rapid onset and a shorter duration of glucose-lowering activity. These pharmacological properties provided the rationale for comparative clinical trials of subcutaneous insulin lispro (administered within 15 minutes before meals, preferably immediately before meals) and subcutaneous human regular insulin (administered 20 to 45 minutes before meals) in patients with type 1 diabetes (insulin-dependent diabetes mellitus) or type 2 diabetes (non-insulin-dependent diabetes mellitus) requiring premeal insulin therapy plus basal insulin therapy. Available clinical trials are well designed and results suggest that 1- and 2-hour postprandial blood glucose levels with insulin lispro are similar to or lower than those with human regular insulin; 1- and 2-hourpostprandial glucose excursions are similar to or less pronounced than those with human regular insulin. Glycated haemoglobin A values were generally similar with both agents. Continuous subcutaneous insulin infusion was associated with greater improvements in postprandial blood glucose levels and glycated haemoglobin A1 values with insulin lispro than with human regular insulin. Confirmatory data are required. The incidence of hypoglycaemia with insulin lispro was similar to or lower than that with human regular insulin. In particular insulin lispro appears to be associated with a lower incidence of night-time and severe hypoglycaemic episodes. Evidence also suggests that patients perceive their quality of life to be improved with insulin lispro compared with human regular insulin, and that satisfaction with treatment is greater with the insulin analogue. Thus, in patients with type 1 or 2 diabetes requiring premeal insulin therapy, insulin lispro appears to provide greater postprandial glycaemic control than human regular insulin without increasing the risk of hypoglycaemia. Furthermore, the reduced injection-meal interval with this agent offers greater convenience for the patient than regular human insulin. If longer term clinical experience supports these promising results it is likely that insulin lispro will offer important advantages over human regular insulin.
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PMID:Insulin lispro: a review of its pharmacological properties and therapeutic use in the management of diabetes mellitus. 933 63

Mutations of the hepatocyte nuclear factor-1 alpha (HNF1 alpha) gene are an important cause of autosomal dominant diabetes with onset before age 25 yr [maturity-onset diabetes of the young (MODY)], and some regions of the HNF1 alpha gene appear to be hot spots for mutations. To evaluate the role of HNF1 alpha in the more common familial type 2 diabetes, we studied 62 families of Northern European origin by linkage analysis and molecular screening. Linkage was rejected under dominant models consistent with either late-onset type 2 diabetes or early-onset dominant diabetes. We used single strand conformation polymorphism analysis to screen 53 diabetic members of 36 families who reported diabetes diagnosed before age 40 yr, 9 members of 2 Utah families with typical MODY, and 24 additional members of families with possible linkage. One MODY family showed the previously reported frameshift mutation (P291fsinsC) in exon 4. Among the individuals with more typical type 2 diabetes, we identified the previously reported common polymorphisms, a new intronic polymorphism, and 3 common amino acid variants. We also identified 2 novel missense mutations that segregated with type 2 diabetes in 1 family each: lysine for glutamic acid substitution at codon 619 in exon 10 (E619K), and an arginine for threonine substitution at codon 537 in exon 8 (R537T) in a second family. The exon 8 mutation showed relatively low penetrance, and the role in this family remains uncertain. No coding mutations were identified in the family members screened on the basis of linkage but without early-onset diabetes. Although HNF1 alpha mutations are not a common cause of familial type 2 diabetes, they may account for 5% of families in which at least 1 member has onset of type 2 diabetes before age 40 yr. Incomplete penetrance and a high sporadic frequency make linkage an inefficient screening tool.
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PMID:Linkage and molecular scanning analyses of MODY3/hepatocyte nuclear factor-1 alpha gene in typical familial type 2 diabetes: evidence for novel mutations in exons 8 and 10. 962 39

Insulin lispro is an analog of human insulin created when the amino acids at positions 28 and 29 of the B-chain of insulin are reversed. The natural sequence in human insulin at these positions is proline at B28 and lysine at B29. At physiologic concentrations, insulin lispro exists in solution as a monomer. As such, it's rate of absorption from subcutaneous sites of injection is greater that of regular insulin. The pharmacokinetic and pharmacodynamic profiles of insulin lispro indicate that it is more rapid-acting, and therefore a more physiological mealtime insulin than regular insulin. In addition, it shows a shorter duration of activity, approximately up to 5 hours. Insulin lispro given 0 to 15 minutes before the meal translate into better glycemic control and less hypoglycemia risk in clinical studies either in type 1 or type 2 diabetes when compare with regular human insulin given 30-45 minutes before meals.
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PMID:[Spanish experience with insulin lispro]. 971 Sep 93

Several tribes of North American Indians are known to have poor glucose control and are at a high risk of developing type 2 diabetes. Similarly some tribes also exhibit RA at a high frequency. We have recently determined that a subset of Caucasian patients with RA mount an immune response to IgG modified with advanced glycation endproducts (AGE). The AGE modifications on IgG in vivo include N(epsilon)-(carboxymethyl) lysine, imidazolone and pentosidine. The presence of IgG-AGE and the antibody response to the IgG-AGE in the Ojibwe tribe of First Nations native Indians where both NIDDM and RA are prevalent was investigated. AGE modified IgG and albumin were determined using a modified nitroblue tetrazolium assay. Rheumatoid factors (RFs) and IgM and IgA anti-IgG-AGE were detected by ELISA. Of the 108 individuals tested, 21 had RA only, 3 had both RA and type 2 diabetes, 30 had type 2 diabetes only and 51 had no diagnosed disease. AGE modified IgG was significantly elevated in the RA group compared to the diabetic group. IgM and IgA RFs were detected in 83% and 50% of the RA patients, compared to 31-37% and 7-10% of the diabetics or normal individuals. IgM anti-IgG-AGE was detected in 54% of the RA patients, in contrast to 7-14% in the diabetics or normal individuals. IgA anti-IgG-AGE was detected in 42% of the RA patients and only 7 to 8% of the NIDDM or normal individuals. The IgM or IgA anti-IgG-AGE antibodies likely contribute to the accumulation of IgG-AGE, possibly through blocked clearance through AGE receptors. A trend towards more severe disease was seen in those Ojibwe RA patients with circulating anti-AGE antibodies. Non-enzymatic glycation may be an important pathogenic link in the RA seen in North American Indians.
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PMID:Advanced glycation endproducts (AGE) on IgG, a target for circulating antibodies in North American Indians with rheumatoid arthritis (RA). 984 95

Since the mid-1980s, a 'mysterious' disease has been afflicting the moose (Alces alces L.) population of south-western Sweden. Molybdenosis combined with secondary copper deficiency syndrome has been suggested as the cause of the clinical signs and of necropsy findings, supported by trace element analysis. Copper deficiency has long been associated with disturbed carbohydrate metabolism and also with oxidative stress. When testing the oxidative stress hypothesis, we found increased concentrations of the glycoxidation products pentosidine and carboxymethyl-lysine (CML), both in plasma proteins and in renal tissue, when compared with control values. The concentration of glycated lysine (furosine), a marker of hyperglycaemia, was also increased. These data, together with elevated insulin levels in affected moose, strongly suggest that they are suffering from an environmentally-induced, non-insulin-dependent type 2 diabetes.
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PMID:A syndrome of molybdenosis, copper deficiency, and type 2 diabetes in the moose population of south-west Sweden. 1081 52

Incubation of bovine aortic endothelial cells (BAECs) with erythrocytes from patients with type 2 diabetes induced an increase in endothelin 1 (ET-1) production. The effect of erythrocytes on ET-1 synthesis was dependent on glycemic control. ET-1 levels after incubation with erythrocytes derived from patients with HbA(1c) levels <6% were just half the levels observed after incubation with erythrocytes from patients with HbA(1c) levels >8%. Nepsilon-(carboxymethyl)lysine (CML)-containing protein isolated from patients' erythrocytes induced ET-1, and CML-containing protein-dependent ET-1 induction was blocked by the recombinant decoy peptide soluble receptor for advanced glycation end products (AGEs), which comprises the NH2-terminal Ig domain of the receptor for AGEs. In vitro-generated AGEs induced ET-1 mRNA transcription (nuclear run-on assay and Northern blot) in a time- and dose-dependent manner. Transient transfection of BAECs with a chimeric construct containing the 5' promoter region of the ET-1 gene linked to a reporter gene confirmed that AGE induced ET-1 promoter activity. Electrophoretic mobility shift assay confirmed AGE-inducible binding of members of the nuclear factor-kappab (NF-kappaB) family to a potential binding site at -2,090 bp. Binding was functionally significant because overexpression of the cytoplasmic inhibitor of NF-kappaB or deletion of the NF-kappaB binding site reduced ET-1 induction, whereas overexpression of NF-kappaB p65 induced ET-1 even in the absence of AGEs. Thus, ET-1 transcription is controlled by the AGE-inducible redox-sensitive transcription factor NF-kappaB.
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PMID:Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE-stimulated cultured endothelial cells. 1096 41


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