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)

Inhibition of glucose-stimulated insulin release by exogenous insulin has been demonstrated in pancreatic islets to be associated with a decrease of the NADPH/NADP ratio and the pentose-phosphate cycle activity. Batches of five islets were incubated for 15 and 90 minutes in 1 ml. of KRB buffer with 2 per cent albumin containing 3 mg./ml. glucose and 0, 200, 400, or 800 microU./ml. of rat insulin, and the glucose-6-phosphate (G6P) and 6-phosphogluconate (6PG) contents were determined by enzymatic cycling. In response to a rise in the concentration of insulin, the 6PG/G6P ratio decreased. A close relationship was observed between this decrease of 6PG/G6P ratio and the net insulin release, the absolute rate of glucose oxidation via the pentose phosphate cycle, and the NADPH/NADP ratios measured under similar conditions. The results suggest that exogenous insulin, directly or indirectly, regulates the pentose cycle activity in the pancreatic islets at the G6P dehydrogenase step.
Diabetes 1977 Sep
PMID:6-Phosphogluconate/glucose-6-phosphate ratio in rat pancreatic islets during inhibition of insulin release by exogenous insulin. 1 30

The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, alpah1-acid glycoprotein, alpha2-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 mug.) used was insufficient to induce synthesis of alpha2-acute phase globulin, net syntheses of albumin, fibrogen, alpha1-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and alpha1-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.
Diabetes 1976
PMID:Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins. 6 Nov 40

To study the effects of improved control of blood glucose on markers of renal glomerular and tubular function, we initially determined, by radioimmunoassay technics, urinary excretion rates of albumin and beta2 microglobulin in 17 nondiabetic subjects and in 43 insulin-dependent, clinically nonproteinuric diabetic patients. Duration of diabetes ranged from six months to 39 years, and the patients were studied while receiving conventional therapy. Mean urinary albumin excretion was significantly elevated in the diabetics, but beta2-microglobulin excretion rates were not different from those of the controls, suggesting that the increased albumin excretion was due to increased transglomerular loss of albumin. Seven patients with long-term diabetes (duration of six to 33 years), selected because of elevated albumin excretion, were studied before and during a continuous, subcutaneous insulin infusion for a period of one to three days. Urinary albumin excretion was significantly reduced during the insulin infusion, but mean beta2-microglobulin excretion did not change. Strict control of blood glucose, even in the short term, may reverse a functional renal abnormality in long-duration, insulin-dependent diabetes.
 ...
PMID:Effect of control of blood glucose on urinary excretion of albumin and beta2 microglobulin in insulin-dependent diabetes. 8 36

Glomerular basement membrane (GBM) thickness was measured in diabetic rats prior to and following islet transplantation. Over the course of the experiment (from 7 to 13 months of diabetes) GBM thickness in diabetic animals exceeded that of littermate controls. After 7 months of diabetes a group of animals received successful intraportal transplants of neonatal pancreatic tissue. GBM thickness at 2 and 6 months following islet transplantation matched the thickness in nontransplanted diabetic rats and exceeded that in control animals. Failure to reverse GBM thickening in diabetic rats following islet transplantation may be due to very slow rates of GBM tunover in the rat. Previous work has demonstrated normalization of urinary albumin excretion after islet transplantation, suggesting that GBM thickening, per se, is not a significant factor causing albuminuria in rats with longstanding diabetes.
 ...
PMID:Glomerular basement membrane thickness following islet transplantation in the diabetic rat. 11 Sep 82

Diabetic glomerulopathy continues as a major problem in the management of the patient with diabetes mellitus; however, evidence in man and in animals underlines the fact that good control of diabetes favorably alters the course of this complication. Islet transplantation in the diabetic rat returns plasma glucose and insulin levels to normal. In parallel mesangial matrix thickening, mesangial deposition of immunoglobulin and urinary excretion of albumin markedly improve following islet transplantation. Although amelioration of diabetes affects the course of glomerulopathy, other factors (most notably measures that increase glomerular capillary pressure) enhance the development of the diabetic renal lesions. Following uninephrectomy or clipping of a renal artery, the remaining (in the case of uninephrectomy) or unclipped diabetic kidney develops the morphologic and functional changes of diabetic nephropathy at a rate greater than in kidneys in an intact diabetic rat. The clipped kidney demonstrates diminished diabetic changes, suggesting a protective effect with decreased glomerular capillary pressures. In addition to measures improving the control of diabetes, procedures reducing factors accelerating diabetic complications may improve the prognosis in diabetic glomerulopathy.
 ...
PMID:The development, enhancement, and reversal of the secondary complications of diabetes mellitus. 11 28

The effect of clofibrate (1.5 g/day) on different plasma proteins and on components of the hemostatic system was studied in eight men with either mild diabetes mellitus or cardiosclerosis. Before treatment, the subjects were investigated weekly on five occasions. The means of these determinations were compared with the values observed after 2, 6 and 14 weeks of treatment. During the treatment albumin and transferrin increased significantly while orosomucoid, ceruloplasmin, beta1 E-globulin, IgA, IgM and fibrinogen decreased significantly. The decreases of the last proteins in per cent were found to be associated with each other in single subjects, i.e. a subject who reacted with a certain degree of change in one protein tended to react in a similar way with regard to the other proteins. A correlation was observed between the concentration before the treatment and the decrease in concentration during the treatment for ceruloplasmin, IgG, IgA, IgM and fibrinogen. The fibrinolytic activity increased significantly. Plasminogen decreased after 6 weeks and increased after 14 weeks of treatment. Platelet adhesiveness was not influenced.
 ...
PMID:Effect of clofibrate on plasma proteins including components of the hemostatic mechanism. 13 Oct 8

The rapid i.v. injection of 60 mg streptozotocin/kg body weight 8 days after an initial dose of 30 mg/kg was the best method to produce a distinct insulin-deficient diabetes in minipigs. Even in the absence of any therapy the further course of this diabetes remained stable without tending to exhibit ketoacidosis. Besides hyperglycaemia and the loss of insulin response to glucose there was significant increase of triglycerides and a decrease of plasma albumin. In the oldest animals this diabetes has so far been observed for more than 3 years. Because of some special advantages this experimental diabetes could provide a useful model for studying diabetic angiopathies.
 ...
PMID:Induction of chronic diabetes by streptozotocin in the miniature pig. 15 15

Insulin has been shown to lower cyclic AMP (cAMP) levels in hormonally sensitive tissue. The mechanism by which this lowering occurs has not yet been fully defined. We studied the effects of insulin on rat adipose tissue cyclic nucleotide phosphodiestrase (PDE) in an incubation system. The adipose tissue used was from both normal animals and animals rendered diabetic by intravenous injections of streptozotocin. Rat epididymal fat pads were incubated in a Krebs-Ringer bicarbonate-4% albumin system with O, 100, 1,000 or 10,000 PU/ml insulin (INS); epinephrine (EPI) or glucagon (GLU) at several different concentrations. After 15 min of incubation, each tissue was homogenized, centrifugated, and the supernatant assayed for cAMP PDE activity using the breakdown of (3-H)cAMP. The data was used to characterize cAMP PDE into apparent high and low K-m PDE components. In the normal animals, INS increased Vmax of the low Km PDE components; 100 pU/ml INS, 30%, 1000 p1/ML INS, 40; and 10,000 pU/ml INS, 20%. In contrast, streptoxotocin diabetes lowered this Vmax by 30%. In the diabetic animals, INS also increased Vmax by 30%. In the diabetic animals, INS also increased Vmax of the low Km PDE component; 100 pU/ml INS, 30%; 1000 pU/ml INS, 50% and 10,000 pU/ml INS, 100%. Epinephrine at 1, 10, and 100 pg/ml stimulated low Km cAMP PDE activity by 67%, 73% and 44% respectively. The stimulatory effect of EPI on both the low and high Km cAMP PDE activity was neutralized by propranolol or adenosine. In comparison to EPI, GLU at very low concentrations, 10-9M, stimulated low Km cAMP PDE. These studies suggest that some of the biologic actions of insulin, an antilipolytic substance, are mediated through activation of low Km PDE. Furthermore, this enzymatic activity is lower in experimental diabetes. The stimulation of low Km PDE by lipolytic hormones may reflect a long-range protective action of these agents.
 ...
PMID:Effect of insulin and lipolytic hormones on cyclic AMP phosphodieterase activity in normal and diabetic rat adipose tissue. 16 58

We have studied the effects of alloxan-induced diabetes and subsequent insulin replacement on albumin and total hepatic protein synthesis. Diabetes resulted in a reduction to approximately 20% of normal in albumin synthesis relative to the rate of total protein synthesis in vivo and a reduction to 10% in the absolute rate of albumin secretion by perfused livers. In contrast, the synthesis of total secretory protein and retained hepatic protein was affected to a lesser extent by diabetes. Treatment of diabetic rats with insulin restored rates of albumin and total hepatic protein synthesis to normal levels. The molecular basis of these alterations in albumin synthesis was investigated by examining albumin mRNA levels in livers of normal, diabetic, and insulin-treated diabetic animals. The level of albumin mRNA, whether assayed by cell-free translation or by hybridization to a specific complementary DNA probe, was markedly decreased in livers of diabetic animals and was restored to normal by insulin treatment. These changes occurred in parallel with changes in the rates of albumin secretion observed in perfused liver, suggesting that albumin mRNA content is the primary factor responsible for altering rates of albumin synthesis under these conditions.
 ...
PMID:Correlation of albumin production rates and albumin mRNA levels in livers of normal, diabetic, and insulin-treated diabetic rats. 28 8

Use of an ion exchange chromatographic method and a colorimetric method with thiobarbituric acid showed that levels of nonenzymatically glucosylated serum albumin were increased in patients with poorly controlled diabetes mellitus compared to controls. The two methods correlated well (r = 0.99) and clearly discriminated between normal and poorly controlled diabetic populations. The levels of glycosylated hemoglobin were also measured in both populations. Several patients apparently in good control based on glycosylated hemoglobin measurements were found to have increased levels of glycosylated albumin. Because albumin has a shorter circulating half-life than does the human erythrocyte, the plasma concentration of glucosylated albumin should be expected to reflect short-term control of hyperglycemia in diabetes. The studies reported here suggest that the level of glucosylated albumin may indeed be a sensitive indicator of moderate hyperglycemia and of early glucose intolerance.
 ...
PMID:Enhanced nonenzymatic glucosylation of human serum albumin in diabetes mellitus. 29 61


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