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

The well known association between non-insulin dependent diabetes mellitus (NIDDM) and hyperlipoproteinemia (HLP) is one of the leading causes of high incidence and mortality for cardiovascular disease of diabetic patients. For auspicious and effective treatment of NIDDM and its complications, secondary prevention, that is, an early detection, plays a major role. At the same time high concern should be given to the benefits of early detection and treatment of atherogenic HLP at early stages of diabetes mellitus, for their occurrence in borderline impairment of glucose tolerance (G-OGT) is still evasive. The investigation on the occurrence and incidence of HLP in G-OGT was carried out in 576 adults (310 men and 266 women) with recently detected G-OGT. The results were compared with those obtained in the non-G-OGT group (50 men and 52 women). Values of total LDL cholesterol as well as triglycerides in the blood of the subjects of either sex highly exceeded recommended values and were higher than in the controls. HDL cholesterol was significantly decreased while the values of the LDL cholesterol/HDL cholesterol ratio and total triglycerides were significantly higher. Atherogenic hyperlipoproteinemia was evidenced in 52.58% of men and 50.75% of women with G-OGT and in 36.00% of men and 32.69% of women with normal G-OGT. After a one-year dietetic regimen all the lipid parameters evidently improved in both men and women, while the incidence of atherogenic hyperlipoproteinemia fell to 40.82% of the men and 31.32% of the women.
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PMID:[The lipoprotein status in persons with borderline glucose tolerance impairment before and after a reducing diet]. 182 43

In 48 patients (age 2-28 years) with documented cystic fibrosis, glucose tolerance was evaluated by means of an oral glucose tolerance test (OGTT) and repeated glycosylated haemoglobin (HbA1C) measurements. An impaired OGTT was found in 15 patients. Their degree of undernutrition and severity of lung and liver involvement were no different from those with normal glucose tolerance. The mean peak insulin concentration as well as the integrated insulin concentration during the OGTT were comparable with patients with normal glucose tolerance (GT) and those with an impaired tolerance (GI). The mean time to attain peak insulin levels was significantly delayed in the GI group. (117 min vs 86 min P less than 0.01). On initial testing, elevated HbA1C levels were found in 22 patients. Mean HbA1C levels in the GI group were higher than in the GT group (8.2% vs 7.5% P less than 0.01). The HbA1C levels at the moment of OGT testing were positively correlated with the glycaemic response during the OGTT. The repeated HbA1C measurements 1 year later were no different from the initial mean HbA1C values in both groups. Two GI patients with initial HbA1C levels of 7.5% and 11% respectively developed diabetes mellitus several months after testing. The need for serial HbA1C determinations in cystic fibrosis is questioned.
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PMID:Oral glucose tolerance testing in cystic fibrosis: correlations with clinical parameters and glycosylated haemoglobin determinations. 204 Mar 47

Many viral infections induce interferon (IFN) production and cause insulin resistance. To examine the causal relationship between IFN and insulin resistance, we injected natural human leukocyte IFN-alpha (3 x 10(6) IU, i.m.) twice overnight in eight healthy subjects and determined oral (OGT) and intravenous (IVGT) glucose tolerance and sensitivity to insulin (287 nmol or 40 mU.m-2.min-1 euglycemic insulin clamp) the following morning. IFN caused mild influenzalike symptoms and induced a rise in circulating glucose, insulin, hydrocortisone (cortisol), growth hormone, and glucagon concentrations (P less than .05-.001). In the OGT test, the area under the glucose curve was 2.6-fold greater (P less than .02), and the disappearance rate of intravenously administered glucose was reduced by 28% (P less than .05) after IFN administration. The impairment in OGT and IVGT occurred despite augmented insulin response. Insulin-stimulated glucose disposal was reduced by 22% (P less than .005), and insulin clearance increased by 18% (P less than .02) after IFN administration. When the insulin-clamp study was repeated in patients with steady-state hyperinsulinemia that was 12% higher (P less than .005) after IFN, the glucose disposal rate was still reduced by 15% (P less than .01). These data indicate that IFN 1) stimulates counterregulatory hormone secretion, 2) impairs glucose tolerance and insulin sensitivity, and 3) stimulates insulin clearance. Thus, IFN may be involved in the development of insulin resistance during viral infections.
Diabetes 1989 May
PMID:Effect of interferon on glucose tolerance and insulin sensitivity. 265 35

The response of VIP to either an oral glucose load (OGT) or intravenous glucose (IV glucose), aimed at reproducing the plasma glucose level after OGT, was studied in trained, conscious, sham-operated (Sham; n = 6) dogs, and dogs having initially (12 months before the glucose experiments) undergone occlusion of the pancreatic duct by the prolamine glue technique (Occ; n = 5). As a result, prior to glucose studies, the exocrine pancreas function was found subtotally reduced, as indirectly evaluated by the para-aminobenzoic acid (PABA) test, but no signs of diabetes were detected. The two studies with glucose administration designed to demonstrate the release of insulin, VIP, somatostatin into plasma as modified by enteric signals (represented by the difference of plasma peptide concentration during OGT minus peptide concentration during IV glucose) revealed the following: (1) basal plasma glucose, insulin, VIP, somatostatin did not differ between Sham and Occ dogs; (2) after OGT in Occ dogs the plasma glucose was elevated, whereas plasma insulin was markedly reduced, and VIP, somatostatin were largely unchanged; (3) the integrated output of insulin only was impaired when considering the so-called entero-insulin axis, while integrated VIP, somatostatin were unaltered. It was concluded (a) the Occ procedure in the dog has the capacity to subtotal destruction of the pancreatic acinar tissue, and of the entero-insular axis of insulin, the latter through yet unknown pathways, (b) the Occ technique may be a useful tool for investigation of the nature of "incretin," (c) VIP and somatostatin do not respond to elevated blood glucose and may have no role in the "incretin" concept of enteric modulation of the B-cell.
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PMID:Long-term pancreatic duct occlusion impairs the entero-insular axis in the dog--failure of plasma VIP to respond as "incretin". 614 19

The risk for healthy sibs to develop type I diabetes is 3-5%. HLA Dr 3 und Dr 4 plus islet-cell antibodies predispose for the disease. Polyuria, polydipsia etc. plus a blood sugar greater than 200 mg/dl establish the diagnosis in symptomatic-and an OGT in asymptomatic patients. Initially non-ketoacidotic patients can be effectively treated with an insulin mixture of 1/3 regular + 2/3 NPH in a dose of 1 U/kg bw per day with 2/3 in the morning and 1/3 in the evening. Manifestation and duration of remission (= no glucose excretion, insulin less than 0.5 U/kg/day, measurable C-peptide) are related to initial decompensation. At present no therapy is available to prolong remission. The "tailored" therapy for diabetics of long duration is favoured: individual insulin mixtures of less than 1 U/kg/day in 2 divided doses, with 6 of more meals. Metabolic control should achieve a glucose excretion of less than 5% of the consumed carbohydrates, a 2-h postprandial blood sugar of less than 200 mg/dl (140-200 mg/dl) and a HbAlc-concentration below 8% (= less than + 3 SD).
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PMID:[Insulin-dependent diabetes: clinical aspects and therapy]. 639 62

Glutamine:fructose 6-phosphate amidotransferase (GFA) is rate-limiting for hexosamine biosynthesis, while a UDP-GlcNAc beta-N-acetylglucosaminyltransferase (O-GlcNAc transferase) catalyses final O-linked attachment of GlcNAc to serine and threonine residues on intracellular proteins. Increased activity of the hexosamine pathway is a putative mediator of glucose-induced insulin resistance but the mechanisms are unclear. We determined whether O-GlcNAc transferase is found in insulin-sensitive tissues and compared its activity to that of GFA in rat tissues. We also determined whether non-insulin-dependent diabetes mellitus (NIDDM) or acute hyperinsulinaemia alters O-GlcNAc transferase activity in human skeletal muscle. O-GlcNAc transferase was measured using 3H-UDP-GlcNAc and a synthetic cationic peptide substrate containing serine and threonine residues, and GFA was determined by measuring a fluorescent derivative of GlcN6P by HPLC. O-GlcNAc transferase activities were 2-4 fold higher in skeletal muscles and the heart than in the liver, which had the lowest activity, while GFA activity was 14-36-fold higher in submandibular gland and 5-18 fold higher in the liver than in skeletal muscles or the heart. In patients with NIDDM (n = 11), basal O-GlcNAc transferase in skeletal muscle averaged 3.8 +/- 0.3 nmol/mg.min, which was not different from that in normal subjects (3.3 +/- 0.4 nmol/mg.min). A 180-min intravenous insulin infusion (40 mU/m2.min) did not change muscle O-GlcNAc transferase activity in either group. We conclude that O-GlcNAc transferase is widely distributed in insulin-sensitive tissues in the rat and is also found in human skeletal muscle. These findings suggest the possibility that O-linked glycosylation of intracellular proteins is involved in mediating glucose toxicity. O-GlcNAc transferase does not, however, appear to be regulated by either NIDDM or acute hyperinsulinaemia, suggesting that mass action effects determine the extent of O-linked glycosylation under hyperglycaemic conditions.
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PMID:UDP-N-acetylglucosamine transferase and glutamine: fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. 902 21

O-Linked GlcNAc addition and phosphorylation may compete for sites on nuclear pore proteins and transcription factors. We sequenced O-linked GlcNAc transferase from rabbit blood and identified the homologous Caenorhabditis elegans transferase gene on chromosome III. We then isolated C. elegans and human cDNAs encoding the transferase. The enzymes from the two species appear to be highly conserved; both contain multiple tetratricopeptide repeats and nuclear localization sequences. The C. elegans transferase accumulated in the nucleus and in perinuclear aggregates in overexpressing transgenic lines. O-Linked GlcNAc transferase activity was also elevated in HeLa cells transfected with the human cDNA. At least four human transcripts were observed in the tissues examined ranging in size from 4.4 to 9.3 kilobase pairs. The two largest transcripts (7.9 and 9.3 kilobase pairs) were enriched at least 12-fold in the pancreas. Based on its substrate specificity and molecular features, we propose that O-linked GlcNAc transferase is part of a glucose-responsive pathway previously implicated in the pathogenesis of diabetes mellitus.
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PMID:O-Linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats. 908 68

It is expected that microvascular blood flow might be affected by blood glucose, blood insulin and C-peptide levels. In our investigation skin microvascular blood flow (LDF) was measured using laser doppler fluxometry at skin temperatures of 37 degrees C and 44 degrees C during a 75 g oral glucose load (OGT) or water in ten healthy volunteers (6 male, 4 female, age: 28.1+/-4.0) who had fasted overnight. The transcutaneous oxygen tension (tcPO2) was measured using a transcutaneous oxygen electrode at a temperature of 44 degrees C. The microvascular response to acetylcholine was investigated before the start of the ingestion period and after 30 minutes. In addition, the capillary blood cell velocity (CBV) was measured using dynamic capillaroscopy. During OGT an increase in LDF could be observed at 37 degrees C (180%, p < 0.005) but only a slight increase was observed at 44 degrees C (86%, n.s.). The microvascular response to acetylcholine increased by 164% (p < 0.05) and the TcPO2 values increased by 30% (p < 0.01) during the OGT investigation. No significant changes in the microvascular measurements could be observed during the water experiment. No significant changes could be observed in the CBV measurements in any phase of the investigation. Plasma C-peptide and insulin levels exhibited an association with the LDF measurements at 37 degrees C (r = 0.22, p < 0.05; r = 0.30, p < 0.05; respectively), whereas blood sugar values showed an association with the TcPO2 measurements (r = 0.39, p < 0.01). After the ingestion of glucose a sophisticated modulation of microvascular blood flow was found in healthy volunteers. Further studies are necessary to investigate the role of a disturbed postprandial blood sugar control, insulin and C-peptide secretion in the development of microvascular dysfunction, especially in IDDM.
Exp Clin Endocrinol Diabetes 1998
PMID:Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals. 1007 23

To explore potential cellular mechanisms by which activation of the hexosamine pathway induces insulin resistance, we have evaluated insulin signaling in conscious fasted rats infused for 2-6 h with saline, insulin (18 mU x kg(-1) x min(-1)), or insulin and glucosamine (30 micromol x kg(-1) x min(-1)) under euglycemic conditions. Glucosamine infusion increased muscle UDP-N-acetylglucosamine concentrations 3.9- and 4.3-fold over saline- or insulin-infused animals, respectively (P < 0.001). Glucosamine induced significant insulin resistance to glucose uptake both at the level of the whole body and in rectus abdominis muscle, and it blunted the insulin-induced increase in muscle glycogen content. At a cellular level, these metabolic effects were paralleled by inhibition of postreceptor insulin signaling critical for glucose transport and glycogen storage, including a 45% reduction in insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation (P = 0.02), a 44% decrease in IRS-1 association with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase (P = 0.03), a 34% reduction in IRS-1-associated PI 3-kinase activity (P = 0.03), and a 51% reduction in insulin-stimulated glycogen synthase activity (P = 0.03). These alterations in postreceptor insulin signaling were time-dependent and paralleled closely the progressive inhibition of systemic glucose disposal from 2 to 6 h of glucosamine infusion. We also demonstrated that glucosamine infusion results in O-linked N-acetylglucosamine modification of IRS-1 and IRS-2. These data indicate that activation of the hexosamine pathway may directly modulate early postreceptor insulin signal transduction, perhaps via posttranslation modification of IRS proteins, and thus contribute to the insulin resistance induced by chronic hyperglycemia.
Diabetes 1999 Aug
PMID:Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle. 1042 74

O-linked N-acetylglucosamine transferase (OGT) catalyzes the attachment ofN-acetylglucosamine (GlcNAc) monosaccharides to the hydroxyl group of serine or threonine residues of intracellular proteins and may play an important role in the hexosamine pathway. Glucose-induced insulin resistance is mediated by increased activity of the hexosamine pathway. In the present study, we examined the localization of OGT mRNA and OGT protein in the rat pancreas. The sites of OGT mRNA expression were determined by in situ hybridization histochemistry with a digoxigenin (DIG)-labeled antisense cRNA probe. Intense hybridization signals were present in the exocrine acinar cells, while weaker ones were detected in the islets of Langerhans. This distribution was confirmed using additional antisense cRNA or oligo-cDNA probes complementary to different regions of OGT mRNA. In addition, immunofluorescence staining with antibody raised against OGT stained both the exocrine acinar cells and endocrine islet cells. In the acinar cell nucleus, the zymogen granule region and contour of the cell were intensely stained. In the islets of Langerhans, especially in the alpha-cells, intense staining with anti-OGT antibody was observed. These staining patterns were almost identical to those seen when staining for the O-linked GlcNAc (O-GlcNAc) modification. Immuno-electron microscopy showed that OGT is localized to the euchromatin of the nucleus and around the secretory granules of exocrine acinar cells and endocrine islet cells. These results suggest that OGT is involved in the regulation of transcription and of granular secretion. Thus, one or more O-GlcNAcylated proteins may be important components of the glucose-sensing mechanism in the pancreas.
Diabetes 1999 Dec
PMID:Localization of the O-linked N-acetylglucosamine transferase in rat pancreas. 1058 Apr 30


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