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)

This article reviews evidence for a pivotal role of glucokinase as glucose sensor of the pancreatic beta-cells. Glucokinase explains the capacity, hexose specificity, affinities, sigmoidicity, and anomeric preference of pancreatic islet glycolysis, and because stimulation of glucose metabolism is a prerequisite of glucose stimulation of insulin release, glucokinase also explains many characteristics of this beta-cell function. Glucokinase of the beta-cell is induced or activated by glucose in contrast to liver glucokinase, which is regulated by insulin. Tissue-specific regulation corresponds with observations that liver and pancreatic beta-cell glucokinase are structurally distinct. Glucokinase could play a glucose-sensor role in hepatocytes as well, and certain forms of diabetes mellitus might be due to glucokinase deficiencies in pancreatic beta-cells, hepatocytes, or both.
Diabetes 1990 Jun
PMID:Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes. 218 59

During hyperinsulinemic glucose-clamp studies, intravenous infusion of calcitonin gene-related peptide (CGRP) in rats antagonized the ability of insulin to stimulate peripheral glucose disposal by 52% (196 +/- 7.2 vs. 105 +/- 10.5 mumol.kg-1.min-1, P less than 0.05) and to inhibit hepatic glucose output by 54% (P less than 0.01). CGRP also inhibited the in vitro effects of insulin to stimulate hexose uptake in cultured BC3H1 myocytes at all insulin concentrations studied. Amylin is a peptide isolated from amyloid deposits in pancreatic islets of type II (non-insulin-dependent) diabetic subjects, is present in normal beta-cells, and bears a striking homology to CGRP. When synthetic human amylin was infused during clamp studies, it inhibited the ability of insulin to stimulate glucose disposal by 56% (96.9 +/- 9.4 vs. 42.4 +/- 5.0 mumol.kg-1.min-1, P less than 0.05) and to suppress hepatic glucose output by 64%. Therefore, amylin and CGRP can cause insulin resistance in vivo and may be implicated in insulin-resistant states such as type II diabetes mellitus.
Diabetes 1990 Feb
PMID:Induction of insulin resistance in vivo by amylin and calcitonin gene-related peptide. 222 35

Structure elucidation of a specific fluorophore from the aging extracellular matrix revealed the presence of a protein crosslink formed through nonenzymatic glycosylation of lysine and arginine residues. The unexpected finding that a pentose instead of a hexose is involved in the crosslinking process suggested that the crosslink, named pentosidine, might provide insight into abnormalities of pentose metabolism in aging and disease. This hypothesis was investigated by quantitating pentosidine in hydrolysates of 103 human skin specimens obtained randomly at autopsy. Pentosidine level was found to increase exponentially from 5 to 75 pmol/mg collagen over lifespan (r = 0.86, P less than 0.001). A three- to tenfold increase was noted in insulin-dependent diabetic and nondiabetic subjects with severe end-stage renal disease requiring hemodialysis (P less than 0.001). Moderately elevated levels were also noted in some very old subjects, some subjects with non-insulin dependent diabetes, and two subjects with cystic fibrosis and diabetes. The cause of the abnormal pentose metabolism in these conditions is unknown but may relate to hemolysis, impaired pentose excretion, cellular stress, and accelerated breakdown of ribonucleotides. Thus, pentosidine emerges as a useful tool for assessment of previously unrecognized disorders of pentose metabolism in aging and disease. Its presence in red blood cells and plasma proteins suggests that it might be used as a measure of integrated pentosemia in analogy to glycohemoglobin for the assessment of cumulative glycemia.
 ...
PMID:End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. 229 12

We have shown that myo-inositol in the cultured rat embryo is diminished whenever malformations are induced by hyperglycemia and that the malformations and reductions of tissue myo-inositol content are not corrected by aldose reductase inhibitors. This study was designed to evaluate the kinetics of myo-[3H]inositol uptake in vitro during 1-, 3-, and 24-h intervals in the 10.5-day rat conceptus (10-12 somites). We found that the equilibration between tissue and medium is relatively slow and that the concentration of free myo-inositol in tissue is only approximately threefold greater than in the medium even after 24 h. The integrated uptake of free myo-inositol by the intact 10.5-day conceptus is a saturable process with a Km (246 +/- 16 microM) consistent with a low-affinity system. The net rate of accumulation into the tissue pool of free myo-inositol exceeds the rate of incorporation of the accumulated myo-inositol into lipid components. Ambient glucose inhibits net myo-inositol uptake in a concentration-dependent fashion, and the inhibition is competitive in nature. The glucose-mediated inhibitions of myo-inositol transport also compromise the concurrent incorporation of myo-[3H]inositol into lipid components, although to a lesser extent. These inhibitory effects are relatively specific for D-glucose and not replicated by equimolar additions of D-mannose or D-galactose. myo-Inositol accumulation by the 10.5-day rat conceptus is also impaired by relatively specific inhibitors of D-glucose transport such as phloridzin or ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 May
PMID:Uptake of myo-inositol by early-somite rat conceptus. Transport kinetics and effects of hyperglycemia. 233 18

The glycosylation of albumin in vitro, as judged from the incorporation of D-[U-14C]glucose into trichloroacetic acid (TCA)-precipitable material represents a time-, temperature- and concentration-related process. It is markedly increased by NaCNBH3. A close correlation is observed between the radioactive data and the percentage of glycosylated albumin, as measured by affinity chromatography. The latter method, however, does not give information on the precise stoichiometry of the protein glycosylation. The relative extent of protein glycosylation can also be estimated by a back-titration procedure, the condensation of labelled D-glucose with the protein being inversely related to its prior degree of glycosylation. The back-titration assay was applied to plasma samples from normal and diabetic rats or human subjects and used to compare the glycosylation of albumin by distinct hexoses and hexose-phosphates. L-Glucose was found as efficient as D-glucose in causing albumin glycosylation and, hence, could conceivably be used to investigate in vivo changes in the intrinsic properties of extracellular proteins secondary to their glycosylation.
Diabetes Res Clin Pract 1990 Jan
PMID:Non-enzymatic protein glycosylation: back-titration assay. 240 27

The solubility of skin collagen into acetic acid and by pepsin digestion and the degree of non-enzymatic glycosylation of collagen (ketoamine linkage) in these fractions was determined in skin specimens from 27 insulin-dependent diabetic subjects and from 17 age-matched controls. Glycosylation in acid soluble collagen specimen was significantly increased in the diabetics, 1.9 +/- 1.8 (SD)ng of hexose/micrograms of hydroxyproline in comparison to the controls. 0.9 +/- 0.8 ng of hexose/micrograms of hydroxyproline. No significant difference in this respect was noted in pepsin soluble collagen specimens. The solubility of collagen into acetic acid and by pepsin digestion were significantly reduced in the diabetics. No clear relationships between non-enzymatic glycosylation or collagen solubility and diabetic late complications (nephropathy, retinopathy or limited joint mobility) were noted. We suggest (a) that equilibrium levels of early glycosylation products are different in acid and pepsin soluble collagen specimens. (b) ketoamine linkage glycosylation products by themselves are not directly involved in diabetic late complications and (c) the solubility in acid and digestibility of collagen by pepsin may be an indicator, even though nonspecific, of increased amounts of advanced glycosylation end products.
Diabetes Res 1989 Jul
PMID:Increased non-enzymatic glycosylation and reduced solubility of skin collagen in insulin-dependent diabetic patients. 262 62

Glycosylated haemoglobin (HbA1C) and serum protein bound hexose (SPBH) levels were estimated in 35 healthy control subjects and 35 diabetic subjects. The mean levels of SPBH in control subjects was 161.69 +/- 3.84 mg/dl. The SPBH levels in diabetic subjects were found to be increased (P less than 0.001). It was not influenced by age and sex of the patients, complications, type of diabetes and treatment received. HbA1C levels in control subjects were 5.33 +/- 0.38/dl. The HbA1C levels in diabetic subjects was found to be markedly elevated (11.95 +/- 0.46/dl) and was found to be highly significant (P less than 0.001). The levels were found to be on higher side in juvenile diabetics. A progressive linear correlation was observed between fasting blood sugar levels and concentration of SPBH and glycosylated haemoglobin concentration. A significant correlation was also observed between the levels of glycosylated haemoglobin and SPBH levels (P less than 0.05).
 ...
PMID:Glycosylated haemoglobin(HbA1C) and serum protein bound hexose in diabetes mellitus. 207 32

We have examined polyol pathway kinetics in the lenses of rats made diabetic with streptozotocin. At up to 11 days after diabetes induction, the lenses were isolated and subjected to 'pulse-chase' studies: the lenses were incubated with [13C]glucose and lens metabolism followed by [13C]nuclear magnetic resonance (NMR) spectroscopy. Proton NMR spectroscopy was also performed to measure the hexose monophosphate shunt (HMPS) activity. The results showed that (1) the activity of aldose reductase increased initially and decreased after 11 days of diabetes; (2) the fructose pool increased initially but started to decline after 3 days; (3) the HMPS activity increased nearly 40% immediately after diabetes induction; and (4) the turnover rates of glucose, alpha-glycerophosphate (GP), lactate, sorbitol, and fructose were 80.8 +/- 2.6, 10.1 +/- 1.4, 47.7 +/- 3.7, 7.9 +/- 0.9 and 5.2 +/- 2.2 nmol hr-1 lens-1 (34 mg wet weight lens-1), respectively. Up to 35% of lactate appeared to derive from the polyol pathway. Further, GP was rapidly metabolized, although its fate is currently unknown. These results reveal a far more complex pattern of glucose metabolism in the diabetic lens than that in lenses incubated in high glucose.
 ...
PMID:Polyol pathway activity in streptozotocin-diabetic rat lens. 275 93

1. Short term (1-2 hr) and long-term (2 days) effects of experimental alloxan induced diabetes on the kinetics of the renal hexose monophosphate shunt dehydrogenases are reported. 2. Alloxan diabetes for 2 days significantly increased kidney weight (16%) adding about 80 mg/day per g of kidney. No significant changes were found in renal growth 1-2 hr after alloxan injection. 3. Under these experimental conditions, the activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase significantly increased (103 and 33% respectively) at all substrate concentrations, without affecting the KmS of either enzyme. 4. There was no effect of alloxan on the activity of these enzymes at 1-2 hr. Saturation curves show that all enzymes exhibited a M-M kinetic without evidence of sigmoidicity. 5. The results suggest that increased renal hexose monophosphate dehydrogenases activities are due to increased concentrations of the rate limiting proteins. 6. The relationship between these changes and renal hypertrophy is also discussed.
 ...
PMID:Influence of experimental diabetes on the kinetic behaviour of renal cortex hexose monophosphate dehydrogenases. 279 53

Transport of the non-metabolizable hexose analogue 3-O-methyl-D-glucose (3OMG) was measured at 37 degrees C, pH 7.4, in human polymorphonuclear leukocytes (PMNLs) obtained from 15 ml of fresh venous blood. In the study, 0.05 mM of 3OMG was equilibrated with a half-time of about 10 s, and the rate constant was 0.074/s in PMNLs from a healthy subject (male, 38 years). The coefficient of variation of values assayed on different days was about 7% and the intra-assay variation was about 2%. The transport rate did not differ between the two sexes or between subjects of different ages (23-63 years), but was significantly higher in 23 patients with non-insulin-dependent diabetes than in 29 normal controls (13.3 +/- 3.7 vs. 10.4 +/- 2.5 fl/cell.s, mean +/- SD). In conclusion, the measurement of transport of 3OMG in PMNLs may be useful for the study of glucose transport in clinical investigations.
Diabetes Res Clin Pract 1989
PMID:Clinical application of measurement of glucose transport in human polymorphonuclear leukocytes. 280 56


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