UMLS:C0011860 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The incretin effect (i.e. the difference between the insulin response after oral and i.v. glucose) is reduced in type 2 diabetes although GIP secretion is normal or exaggerated. This suggests an insensitivity of the diabetic B-cell to GIP. However, it could also indicate the lack of another not yet defined "incretin". 2. While CCK is a potent incretin in rats and dogs, physiological concentrations of this hormone do not stimulate insulin secretion in man in presence of elevated blood levels of glucose or phenylalanine in the physiological range. It also does not interact with GIP. 3. Glucagon-like peptide I (7-36) is a potent glucose-dependent stimulator of insulin secretion in animals and man. Preliminary data suggest release after oral glucose despite localization of the GLPI containing cells predominantly in the ileum and colon. More data are needed before GLPI (7-36) can be regarded as a physiological incretin and its role in type 2 diabetes assessed.
...
PMID:Entero-insular axis and diabetes mellitus. 149 Jun 80

Calcium- and phospholipid-dependent protein kinase (protein kinase C; PKC) may be an important mediator in transduction of some of the cellular actions of insulin. We studied PKC activity in freshly isolated circulating mononuclear cells obtained from healthy subjects and patients with non-insulin-dependent (type II) diabetes mellitus (NIDDM). The kinase activity was measured using a specific nonapeptide substrate, Ala-Ala-Ala-Ser-Phe-Lys-Ala-Lys-Lys-amide. There was negligible calcium- and phospholipid-independent kinase activity in cytosolic and particulate fractions of cells from both control and diabetic subjects. Total (cytosolic and particulate) PKC activity of mononuclear cells from poorly controlled diabetic patients was significantly reduced compared with controls; this reduction was mainly due to a decrease in the cytosolic kinase activity. Tumor-promoting phorbol ester (TPA, 0.1 mumol/L) induced translocation of PKC activity in control cells; in contrast, this subcellular redistribution was not observed in cells from a majority of poorly controlled diabetic subjects. Increased calcium influx into the cells caused by the calcium ionophore A23187-triggered translocation of PKC activity in control cells, while it was ineffective in cells from poorly controlled diabetic patients. Cells from well-controlled diabetic patients demonstrated TPA-induced translocation of the PKC activity approaching that of control cells. The total PKC activity in cells from patients with good glycemic control was normal. Impaired activation of PKC is thus associated with the insulin resistance found in patients with poorly controlled NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Impaired translocation of protein kinase C activity in human non-insulin-dependent diabetes mellitus. 186 31

Human hexokinase (HK) II, a glucose phosphorylating enzyme in muscle tissue, plays a central role in glucose metabolism. Since reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate content in muscle have been demonstrated in pre-non-insulin-dependent diabetes mellitus (pre-NIDDM) and NIDDM subjects, we have examined the coding region of the HKII gene in NIDDM patients to determine whether these patients show genetic polymorphisms that are associated with or contribute to the disease. Single-strand conformational polymorphism analysis and nucleotide sequencing were initially performed on the entire coding region of the HKII gene of 38 insulin-resistant NIDDM patients and 5 healthy control subjects. This analysis revealed four missense mutations at codons 142 (Gln to His), 148 (Leu to Phe), 497 (Arg to Gln), and 844 (Arg to Lys) and an additional six exon polymorphisms that did not predict any change in amino acid composition of the protein. One homozygous and nine heterozygous carriers of the codon 142 mutation were found among the NIDDM patients. The mutations at codons 148, 497, and 844 were each found in one diabetic subject and only on one allele. There were no carriers of compound heterozygous mutations. A subsequent study of 301 patients with NIDDM and 151 healthy control subjects revealed no additional mutations at codons 148, 497, or 844. The total frequency of the mutated allele at codon 142 was 18.9% among the control subjects and 17.0% among the NIDDM patients (chi 2 = 0.56, P = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity. 788 23

The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation with phorbol myristate acetate (PMA), n-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP), aggregated human IgG, or Staphylococcus aureus was determined in 36 patients with non-insulin dependent diabetes mellitus (NIDDM). H2O2 production by PMN after stimulation was measured using flow cytometry. Thirty-six patients with NIDDM were divided into four stages as follows: 1) stage I: non-microalbuminuric stage; 2) stage II: microalbuminuric stage; 3) stage III: proteinuric stage without impairment of renal function; and 4) stage IV: proteinuric stage with impairment of renal function. H2O2 production after PMA stimulation in all stages of NIDDM patients was higher than that in healthy controls. This increase of H2O2 production by PMN was particularly observed in stage IV of NIDDM patients after stimulation. Furthermore, H2O2 production in patients in stage IV was higher than that in patients with non-diabetic disease with impairment of renal function. It appears that reactive oxygen species produced by PMN after stimulation under some conditions may play an important role in the progression of diabetic nephropathy.
...
PMID:Production of hydrogen peroxide by neutrophilic polymorphonuclear leukocytes in patients with diabetic nephropathy. 836 Jul 96

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H]glucose (20 microCi, 0.2 microCi/min), [U-14C]glutamine (20 microCi, 0.2 microCi/min), [3-13C]alanine (99% 13C, 2 mmol, 20 micromol/min), [ring-2H5]phenylalanine (99% 2H, 2 micromol/kg, 0.03 micromol x kg(-1) x min(-1)), and limb balance techniques. Alanine turnover (4.54 +/- 0.24 vs. 5.64 +/- 0.33 micromol x kg(-1) x min(-1)), de novo synthesis (3.00 +/- 0.25 vs. 4.01 +/- 0.33 micromol x kg(-1) x min(-1)), and conversion to glucose (1.02 +/- 0.09 vs. 1.56 +/- 0.17 micromol x kg(-1) x min(-1)) were increased in NIDDM subjects (all P < 0.01), while its forearm release (0.45 +/- 0.04 vs. 0.39 +/- 0.04 micromol x kg(-1) x min(-1)) was unaltered. Although glutamine turnover (4.81 +/- 0.23 vs. 4.40 +/- 0.31 micromol x kg(-1) x min(-1)) was unaltered in NIDDM, its conversion to glucose (0.57 +/- 0.04 vs. 1.08 +/- 0.10 micromol x kg(-1) x min(-1)) and to alanine (0.10 +/- 0.01 vs. 0.34 +/- 0.04 micromol x kg(-1) x min(-1)) (both P = 0.001) was increased while its oxidation (2.84 +/- 0.27 vs. 1.84 +/- 0.15 micromol x kg(-1) x min(-1), P = 0.03) and forearm release (0.77 +/- 0.05 vs. 0.62 +/- 0.09 micromol x kg(-1) x min(-1), P < 0.008) were both reduced. Our results thus demonstrate that there are substantial alterations of glutamine and alanine metabolism in NIDDM. Conversion of both amino acids to glucose and the proportion of their turnover used for gluconeogenesis are increased; release of both amino acids from tissues other than skeletal muscle seems to be increased. Finally, the reduction in glutamine oxidation, possibly the result of competition with glucose and free fatty acids as fuels, makes more glutamine available for gluconeogenesis without a change in its turnover.
...
PMID:Glutamine and alanine metabolism in NIDDM. 866 34

Two novel oral hypoglycaemic agents, NN623 and A4166, have been developed and are now in phase II clinical trial. Both agents have several common characteristics from sulphonylureas. NN623 is a stereoisomer of derivatives of benzoic acid and A4166 is also a stereoisomer of phenylalanine derivative. The predominant mechanism of the action is thought to be like sulphonylureas. Both NN623 and A4166 occupy, at least partly, a common receptor site with glibenclamide and close the ATP-dependent K+ channel. They are rapidly absorbed from the intestine and are eliminated mainly into the bile. NN623 is about 10 times more potent in hypoglycaemic action than glibenclamide and 100 times more than A4166 in terms of dosage. When 1.0 mg NN623 or 60 mg A4166 was given orally in the post-absorptive state to healthy volunteers, both agents evoked hypoglycaemia by 40 min. The duration of hypoglycaemia after NN623 was longer than after A4166 by about 1 hour. The effect of food on their bioavailability is similar. Food has marked influence on the absorption of both drugs and on their efficacy. When 1 mg of NN623 or 60 mg of A4166 was administered just before the meal, Tmax of NN623 and A4166 was 34 +/- 18 min and 18 +/- 6 min, while T1/2 was 0.64 +/- 0.12 h and 0.98 +/- 0.06 h, respectively. The postprandial rise in plasma glucose was reduced at 45 min and thereafter over 4-h after 1.0 mg NN623 and at 30 min to 90 min after 60 mg A4166. Plasma insulin levels rose more than those after placebo from 30 to 90 min after NN623 and at 20 to 40 min after A4166. Both agents stimulated insulin release much more in the postprandial than in the fasting state. There was no difference in the bioavailability after 5 or 7 days of administration. However, when administered immediately after the meal, the absorption of both drugs was delayed and the rise in plasma absorption was not suppressed until 60 min after the meal. Both fasting and postprandial hyperglycaemia were reduced after 1 to 4 weeks of premeal treatment with 0.5 mg NN623 or 60 mg A4166 in subjects with NIDDM. Plasma glucose levels were decreased over 4 h after NN623 and over 1 h after A4166. The meal-induced insulin response was almost doubled by NN623 over 2 h and 1 h by A4166. There was no difference in the bioavailability after breakfast between the first and last administrations of both drugs. In conclusion, a rapid rise in plasma insulin levels is associated with the suppression of postprandial hyperglycaemia.
...
PMID:Modulation of insulin secretion in non-insulin-dependent diabetes mellitus by two novel oral hypoglycaemic agents, NN623 and A4166. 889

To evaluate whether granulocyte-colony stimulating factor (G-CSF) improves an impaired production of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients, we studied the effect of G-CSF on myeloperoxidase (MPO) activity and chemiluminescence amplified by a Cypridina luciferin analog (CLA-DCL), which is dependent on O2 generation, and luminol (L-DCL), which is dependent on OCl(-) generation, in response to formyl-methonyl-leucyl-phenylalanine. Both CLA-DCL and L-DCL by neutrophils from the diabetic group (n = 15, HbA(1c) >10%) were significantly decreased (26 and 37%, respectively: P < 0.01) compared with the age-matched normal control group (n = 15), and L-DCL was more sensitive to this inhibition than CLA-DCL (P < 0.05). In both control and diabetic neutrophils, G-CSF significantly enhanced both CLA-DCL (175% in control and 156% in diabetic) and L-DCL (283% in control and 346% in diabetic). In diabetic neutrophils, the enhancing effect of G-CSF on L-DCL was more sensitive than on CLA-DCL (P < 0.001). There was a positive correlation between HbA(1c) and the enhancing effect of G-CSF on L-DCL in diabetic patients (P < 0.05), but not on CLA-DCL. MPO activity was also decreased in the diabetic group (63%, P < 0.05), and G-CSF improved this impaired MPO activity (184%, P < 0.01). Furthermore, there was a positive correlation between HbA(1c) and the improving effect of G-CSF on MPO activity (P < 0.05). Because bacterial infection still accounts for an important cause of morbidity and mortality in diabetic patients, these data suggest that G-CSF may be useful as a drug to prevent the aggravation of bacterial infection by improving neutrophil function, especially through H2O2-MPO-OCl(-) mechanism, in poorly controlled diabetic patients.
...
PMID:Effect of granulocyte-colony stimulating factor on generation of oxygen-derived free radicals and myeloperoxidase activity in neutrophils from poorly controlled NIDDM patients. 897 Oct 93

Psammomys obesus fed a high-calorie diet develops a NIDDM-like syndrome. The use of reverse-phase high-performance liquid chromatography (HPLC) to study Psammomys insulin biosynthesis and release revealed a very delayed elution time for the Psammomys insulin peak appearing near the position of human proinsulin. This unusual peak was initially thought to represent partially processed insulin on the basis of its molecular size and susceptibility to trimming by carboxypeptidase B (CpB). However, the findings of an active carboxypeptidase E (CpE) enzyme and the normal amidated forms of gastrin and cholecystokinin octapeptide (CCK-8) in Psammomys tissues were inconsistent with CpE-related aberrant processing of insulin. Moreover, amino acid sequencing of the delayed peak of Psammomys insulin revealed fully processed insulin with amino acid sequence as predicted by the cDNA. The unique presence of a B-30 phenylalanine residue, resulting in an increased hydrophobicity of the insulin molecule, probably underlies the marked delay in elution time on HPLC. The unusual structure of Psammomys insulin does not appear to contribute to the proinsulinemia observed in diabetic Psammomys since the HPLC-purified molecule did not inhibit PC1 and PC2 convertase activities in an in vitro assay.
...
PMID:Characterization of the unusual insulin of Psammomys obesus, a rodent with nutrition-induced NIDDM-like syndrome. 916 65

Selected esters of succinic acid are currently under investigation as possible insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus. Novel esters with high insulinotropic efficiency were recently synthesized. The present study concerns the effects of two of these novel esters, namely glycerol-1,2-dimethylsuccinate (2.5 mM) and propanediol-1,2-dimethylsuccinate (1.0 mM), upon the release of insulin and the de novo biosynthesis of peptides in islets from hereditarily diabetic Goto-Kakizaki rats. Whereas D-glucose (2.8 to 16.7 mM) caused a concentration-related stimulation of insulin release in the islets of the diabetic rats, the two esters of succinic acid only increased modestly, and often not significantly, insulin secretion. Nevertheless, they both markedly increased the incorporation of L-[4-3H]phenylalanine into trichloroacetic acid-precipitable material in islets deprived of any other exogenous nutrient. These findings indicate that, at variance with all pharmaceutical agents presently used or proposed as insulin secretagogues in the treatment of type 2 diabetes, glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate, considered as islet cell nutrients, display, in addition to their insulinotropic action, the property of stimulating biosynthetic activity in the endocrine pancreas of animals affected by this disease.
...
PMID:Effects of glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate on insulin release and protein biosynthesis in islets of Goto-Kakizaki rats. 943 19

To explore the possibility that b type recombinant human granulocyte-colony stimulating factor (rhG-CSF) is a useful drug to prevent the morbidity and mortality caused by infections in diabetic patients, we have studied effects of rhG-CSF on chemiluminescence amplified by a luciferin analog (CLA-DCL) and luminol (L-DCL) in response to formyl-Methionyl-Leucyl-Phenylalanine (fMLP) in neutrophils from patients with non insulin dependent diabetes mellitus (NIDDM) (diabetic neutrophils) and healthy subjects (control neutrophils). Both CLA-DCL and L-DCL in diabetic neutrophils were significantly reduced, and L-DCL was more sensitive to this suppression than CLA-DCL. RhG-CSF did not change the basal chemiluminescence in control and diabetic neutrophils, but it primed CLA-DCL and L-DCL. Although, in diabetic neutrophils, the priming effect of rhG-GSF on both CLA-DCL and L-DCL was less compared to that in control neutrophils, L-DCL was more sensitive to this priming effect than CLA-DCL. Because bacterial infection is still an important cause of the morbidity and mortality in diabetic patients, these data suggest that rhG-CSF is a useful drug to prevent the aggravation of bacterial infection in patients with NIDDM.
...
PMID:Improvement of an impaired chemiluminescence response to formyl-methionyl-leucyl-phenylalanine in neutrophils from patients with non insulin dependent diabetes mellitus by recombinant human granulocyte-colony stimulating factor. 1058 72

1 2 3 4 5 6 7 8 9 10 Next >>