Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel mutation Arg1131-->Gln in the catalytic loop of insulin receptor (IR) associated with insulin resistant diabetes was detected. A 56-year-old male with hyperinsulinemia (fasting IRI 92 microU/ml) showed moderate impairment in glucose tolerance (HbAlc 7.0%, fructosamine 258 mumol/l, fasting glucose 119 mg/dl, maximum value of blood glucose during 75 g OGTT 220 mg/dl). While insulin binding to erythrocytes IR was normal, the insulin-induced autophosphorylation of the patient's erythrocytes IR in vivo showed marked decrease, suggesting this patient had some defect in the kinase domain (exon 17-21) of IR. PCR-SSCP analysis of kinase domain with a genomic DNA obtained from the patient's leucocytes indicated the presence of some mutations in exon 19. Sequencing analysis in M13 revealed a heterozygous mutation at a position 1131 (CGG-->CAG) substituting Gln for Arg. Four people of patient's family analyzed are revealed to have an identical missense mutation at the same position with the patient.
 ...
PMID:[Insulin receptor Arg1131-->Gln: a novel mutation in the catalytic loop of insulin receptor observed in insulin resistant diabetes]. 147 Jan 63

According to recent evidence, the presence of an Arg residue at position 52 in the HLA-DQ alpha chain may confer susceptibility to Type 1 diabetes and thus be possibly used to define quantitatively the genetic risk of this disease. Arg52 and non-Arg52 DQA1 alleles cannot be typed by the conventional cytotoxicity test and they must be distinguished at the genomic level. We describe a simple procedure which discriminates the DQA1 alleles based on the differential electrophoretic migration of the DNA heteroduplexes they form with a reference DNA fragment. A major advantage of this procedure is the fact that no hybridization probe is required. Practically, this typing procedure consists of an electrophoretic run of the products of a selective PCR in polyacrylamide gel.
 ...
PMID:Probe-less genomic typing of Arg52 (type 1 diabetes-associated) and non-Arg52 (non-type 1 diabetes-associated) HLA-DQA1 alleles. 147 36

A review of findings pertaining to EDRF (endothelium derived relaxation factor) which proved to be nitric oxide, NO. After an account of the vasodilatating action of NO in the cardiovascular system the main attention is devoted to macrophages, the source of NO and to the formation of NO during activation of infections and during septic shock. NO participates also in the cytotoxicity of macrophages. NO may be the cause of hypotension in hepatic failure. Cumulation of endogenous inhibitors of NO formation in renal failure may be the cause of hypertension. The author analyzes other clinical effects of NO with regard to impotence and diabetes: NO stimulates insulin secretion from the B-cells of the islets of Langerhans. Attention is also drawn to the possible function of NO in the pituitary, in particular with regard to the arginine test which stimulates STH secretion.
 ...
PMID:[A new agent--nitric oxide]. 148 81

The effect of L-arginine on the arginase activity and polyamine levels was studied in the pancreas of normal and diabetic rats (120 mg/kg alloxan, i.v.). Four groups were formed (10 male adults per group). I-Control-0.154 M NaCl. II-Diabetic-0.154 M NaCl (96 h after alloxan). III-Control plus 10 mM L-arginine IV-Diabetics plus 10 mM L-arginine. Rats were sacrificed 20 min after L-arginine injection. Glucose in serum and dry weight, proteins, arginase activity and polyamines (HPLC) in pancreas were measured. Higher ratio mg protein/mg dry weight and arginase induction was observed for groups III and IV. Putrescine was low as a consequence of diabetes but restored with L-arginine. The concentrations of spermidine and spermine were lower. These results may suggest that arginine is metabolized to putrescine in the pancreas and that polyamines may be utilized in regenerating processes or for recovering the endocrine pancreatic function.
 ...
PMID:Effect of L-arginine on pancreatic arginase activity and polyamines in alloxan treated rats. 148 95

Susceptibility to insulin-dependent diabetes mellitus (IDDM) correlates with the absence of aspartic acid in position 57 of the DQB1 and/or the presence of arginine in position 52 of the DQA1. It has been postulated that transcomplementation between the DQ alpha and beta chains of the two haplotypes could create new molecules conferring susceptibility to IDDM. Finland has the highest incidence of IDDM in the world (35/100,000). In a nationwide study of IDDM in childhood (DiMe study) HLA genotyping using conventional serology was carried out according to genetic-epidemiological principles. We simulated DQA1 and DQB1 alleles in 707 consecutively diagnosed IDDM probands and 98 non-diabetic children based on serology, restriction fragment length polymorphism results and sequence data assuming no recombination between DQ and DR. In 34% of Finnish children with IDDM all four combinations (two in cis and two in trans) could lead to SS heterodimers. Two-thirds of these combinations were explained by DR3,DR4 heterozygotes. In 50% of IDDM children half and in 11% a quarter of the combinations could lead to heterodimers. In 38 IDDM patients (5%) the formation of hybrid molecules was not possible. In 59% of the controls SS heterodimers were possible and should therefore have an underlying genetic susceptible for IDDM assuming the theory of transcomplementation is correct. These findings, together with the fact that the lowest frequency of DR3,DR4 heterozygosity (21%) was seen in Finland, show that heterozygosity for DQ and DR cannot explain the differences seen in IDDM incidence.
 ...
PMID:DQA1 and DQB1 heterodimers in insulin-dependent diabetes mellitus: a genetic-epidemiological study in Finland. DiMe Study Group. 148 50

Autotransplantation of islets of Langerhans has resulted in long-term normoglycemia in pancreatectomized dogs. This canine model is useful in evaluating both the progress of islet transplantation and the effect of a reduced islet mass upon the determinants of glucose tolerance: i.e., insulin secretion, insulin sensitivity, and glucose effectiveness. To determine the effect of a reduced islet mass on these factors, we measured the acute insulin response to arginine (AIRa) and glucose (AIRg), the slope of glycemic potentiation of AIRa (SP), insulin sensitivity (Sl), and glucose effectiveness (SG) in control (CN), diabetic (DM), and pancreatectomized dogs rendered normoglycemic with transplanted autografts of islets of Langerhans (TX). Normal fasting plasma glucose (FPG) (TX 4.7 +/- 0.2 mM; CN 4.9 +/- 0.1 mM; P greater than 0.05) was maintained despite a markedly reduced insulin secretion in TX (AIRa 24%, AIRg 15%, and SP 11% of CN). All measures of insulin secretion were significantly correlated (SP vs. AIRg, r = 0.80, P less than 0.0001; AIRa vs. AIRg, r = 0.92, P less than 0.0001) across all animals, but none of the measures of secretion were significantly correlated with either the number of islets transplanted or time posttransplant (P greater than 0.10). Insulin sensitivity was normal in islet autografted dogs (TX: 136 +/- 12 min-1/(nmol/ml); CN: 101 +/- 11 min-1/(nmol/ml), P greater than 0.05) but SG was reduced (TX: 1.93 +/- 0.28 x 100 min-1; CN: 3.53 +/- 0.35 x 100 min-1, P less than 0.05), as determined by the minimal-model method. In diabetic animals (FPG = 16.1 +/- 1.3 mM), insulin secretion was negligible by all measures (P greater than 0.05), and was associated with insulin resistance (Sl = 28 +/- 8 min-1/(nmol/ml)) and reduced SG (1.72 +/- 0.11 x 100 min-1). These studies indicate that across a range of insulin secretion in dogs, the secretagogues arginine and glucose provide similar estimates of beta-cell function. This markedly reduced beta-cell function does not result in insulin resistance when fasting normoglycemia is maintained, but is associated with a decrease in glucose action at basal insulin.
Diabetes 1992 Sep
PMID:Markedly reduced beta-cell function does not result in insulin resistance in islet autografted dogs. 149 68

DNA polymorphisms in the glucokinase gene have recently been shown to be tightly linked to early-onset non-insulin-dependent diabetes mellitus in approximately 80% of French families with this form of diabetes. We previously identified a nonsense mutation in exon 7 in one of these families and showed that it was the likely cause of glucose intolerance in this dominantly inherited disorder. Here we report the isolation and partial sequence of the human glucokinase gene and the identification of two missense mutations in exon 7, Thr-228----Met and Gly-261----Arg, that cosegregate with early-onset non-insulin-dependent diabetes mellitus. To assess the molecular mechanism by which mutations at these two sites may affect glucokinase activity, the crystal structure of the related yeast hexokinase B was used as a simple model for human beta-cell glucokinase. Computer-assisted modeling suggests that mutation of Thr-228 affects affinity for ATP and mutation of Gly-261 may alter glucose binding. The identification of mutations in glucokinase, a protein that plays an important role in hepatic and beta-cell glucose metabolism, indicates that early-onset non-insulin-dependent diabetes mellitus may be primarily a disorder of carbohydrate metabolism.
 ...
PMID:Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus. 150 86

The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2). In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo. Thus, nicardipine did not produce any significant overall alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects.
 ...
PMID:Nicardipine does not cause deterioration of glucose homoeostasis in man: a placebo controlled study in elderly hypertensives with and without diabetes mellitus. 150 7

The endothelium plays a pivotal role in modulating the reactivity of vascular smooth muscle through the formation of several vasoactive substances. We examined the effects of endothelium-dependent and independent vasodilators on forearm blood flow in 29 patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 21 control subjects, using venous occlusion plethysmography. Via a brachial artery cannula, increasing amounts of acetylcholine and glyceryl trinitrate were infused in doses of 60, 120, 180 and 240 mmol per min and 3, 6 and 9 nmol per min respectively. NG monomethyl-L-arginine, a stereospecific inhibitor of endothelium derived relaxing factor, was infused to inhibit basal and stimulated release of this dilator substance. Reactive hyperaemic forearm blood flow did not differ between groups. Forearm blood flow responses to each dose of acetylcholine were significantly greater in control than diabetic subjects (p less than 0.01 for all doses). NG monomethyl-L-arginine attenuated forearm blood flow from maximal stimulated values when responses were compared with the natural decline to acetylcholine in forearm flow in both control and diabetic subjects (p less than 0.05 for both groups), but had no effect on basal blood flow responses. Forearm blood flow responses to each dose of glyceryl trinitrate were significantly greater in control than diabetic subjects (p less than 0.05 for all). These data provide evidence for endothelial and smooth muscle dysfunction in diabetes which may have important therapeutic implications.
 ...
PMID:Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. 2226 97

Non-insulin-dependent diabetes was obtained in rabbits following pancreatic duct ligation. The insulin responses to D-glucose and to L-arginine were studied in the isolated perfused pancreas of control, prediabetic, and diabetic rabbits. In controls, D-glucose or L-arginine caused biphasic insulin release that was qualitatively and quantitatively altered in both prediabetic and diabetic animals. Most secretagogues influence the islet response to other secretagogues by modifying the B-cell memory. In perfused control pancreas, the priming effect of D-glucose resulted in a time-dependent potentiation (TDP) of insulin release during subsequent L-arginine stimulus, whereas L-arginine induced a time-dependent inhibition (TDI) of insulin release during subsequent D-glucose stimulus. As compared with the controls, the TDP effect obtained was emphasized in prediabetic and strongly diminished in diabetic animals. In some prediabetic and diabetic cases, the TDI remained unchanged compared with the controls, and in others it diminished in prediabetic and disappeared in diabetic animals where the effect became one of TDP. The effects of TDP and TDI seem to evolve independently of the modifications of the responsiveness to B-cell secretagogues.
 ...
PMID:Responsiveness and memory of the pancreatic B-cells to the insulin secretagogues D-glucose and L-arginine in prediabetic and diabetic rabbits. 151 6


<< Previous 1 2 3 4 5 6 7 8 9 10