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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of [Ca2+]i-activated K+-channels in the pancreatic beta-cell membrane is based in two observations: quinine inhibits K+-permeability and, increasing intracellular Ca2+ stimulates it. The changes in K+-permeability of the beta-cell have been monitored electrically by combining measurements of the dependence of the membrane potential on external K+ concentration and input resistance. The changes in the passive 42K and 86Rb efflux from the whole islet have been measured directly. Intracellular Ca2+ has been increased by various means, including increasing extracellular Ca2+, addition of the Ca2+-ionophore A23187 or noradrenaline and application of mitochondrial uncouplers and blockers. In addition to quinine, many other substances have been found to inhibit or modulate the [Ca2+]i-activated K+-channel. The most important of these is the natural stimulus for insulin secretion, glucose. Glucose may inhibit K+-permeability by lowering intracellular Ca2+. Glibenclamide, a hypoglycaemic sulphonylurea, is about 25 times more active than quinine in blocking the K+-channel in beta-cells. The methylxanthines, c-AMP, various calmodulin inhibitors and Ba2+ also inhibit K+-permeability. Genetically diabetic mice have been studied and show an alteration in the [Ca2+]i-activated K+-channel. It is concluded that the [Ca2+]i-activated K+-channel plays a major role in the normal function of the pancreatic beta-cell. The study of its properties should prove valuable for the understanding and treatment of diabetes.
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PMID:Properties of the Ca-activated K+ channel in pancreatic beta-cells. 632 7

Using serum-deprived monolayers of bovine aortic endothelial cells that were disrupted experimentally with a linear wound, we observed, by immunofluorescence microscopy, centrosomal perinuclear movement that is associated closely with cell orientation and locomotion. In the presence of the growth factors fetal bovine serum, insulin, or multiplication-stimulating activity (MSA), the centrosome rapidly (within 10 s) translocated and positioned itself between the nucleus and wound track in greater than or equal to 70% of cells bordering the wound. Random centrosomal orientation was observed in control border cells (50%). This growth factor-stimulated centrosomal orientation response to wounding depended on growth factor concentration, high-energy phosphates, functional microtubules and microfilaments, and calcium-calmodulin interaction. In the absence of fetal bovine serum, insulin, or MSA, the border cells of the wounded endothelial cell monolayer exhibited a significant centrosomal orientation response 5-6 h after wounding.
Diabetes 1984 Nov
PMID:Insulin and multiplication-stimulating activity induce a very rapid centrosomal orientation response to wounding in endothelial cell monolayers. 638 26

Both the calcium ion and calmodulin have been proposed to play a role in producing the intracellular effects of insulin. Abnormalities in calmodulin levels have previously been reported in tissues from diabetic animals. Thus, using a sensitive and specific radioimmunoassay, we measured calmodulin levels in red cells and polymorphonuclear leukocytes from humans with diabetes mellitus. Diabetic patients have significantly lower white cell calmodulin levels than age-matched controls. There were no significant differences in red cell calmodulin levels in diabetics compared with controls. Red cell calmodulin levels in normal subjects were decreased with advancing age. We conclude that the alteration in calmodulin levels in leukocytes from diabetics may be associated with the decreased neutrophil function that has been observed in diabetics.
Diabetes 1984 Jan
PMID:The effects of aging and diabetes mellitus on human red and white cell calmodulin levels (chemotaxis/phagocytosis/calcium). 669 Mar 46

Red blood cell (RBC) and polymorphonuclear white blood cell (WBC) calmodulin levels were measured in 25 uremic patients on regular hemodialysis. Uremic patients had significantly higher RBC [11.45 +/- 0.66 (+/-SE) fg/cell] and WBC (590.5 +/- 110 fg/cell) calmodulin levels than normal subjects (8.62 +/- 0.37 and 130 +/- 30 fg/cell; P less than 0.05). An extremely high RBC calmodulin level (20.58 fg/cell) was found in a patient with sickle cell anemia. Uremic patients on dialysis for 2 yr or more had lower RBC (10.99 +/- 0.58 fg/cell) and WBC (390 +/- 50 fg/cell) calmodulin levels than those who were on dialysis for less than 2 yr (RBC, 12.30 +/- 1.56 fg/cell; WBC, 943 +/- 256 fg/cell; P less than 0.05). There were no statistically significant differences in calmodulin levels when different subgroups of uremic patients were compared, e.g. patients with diabetes mellitus or those receiving supplemental vitamin D, anabolic steroids, or antihypertensive medications. We conclude that calmodulin levels are elevated in uremic patients on regular hemodialysis.
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PMID:The effects of chronic renal failure and hemodialysis on human red and white cell calmodulin levels. 672 5

The effects of Ca2+-calmodulin on adenylate cyclase activity in EGTA-washed, 27000 g particulate fractions of mouse and rat pancreatic islets were studied. Ca2+ (10 microM)-calmodulin (1 microM) stimulated adenylate cyclase activity 53.1 +/- 5.2 (N = 6)% in the particulate fraction of rat islets. Trifluoperazine (50 microM), a specific inhibitor of calmodulin, inhibited the Ca2+-calmodulin activation of the adenylate cyclase activity of this fraction of rat islets. These results confirm previous reports dealing with Ca2+-Calmodulin and rat islet adenylate cyclase [Valverde, Vandermeers. Anjaneyulu & Malaisse (1979) Science 206, 225-227; Sharp, Wiedenkeller, Kaelin, Siegel & Wollheim (1980) Diabetes 29, 74-77]. In contrast, however, Ca2+ (1-100 microM)-calmodulin (1-10 microM) did not stimulate the adenylate cyclase activity in the EGTA-washed particulate fraction of mouse islets, and trifluoperazine (50 microM) did not inhibit the adenylate cyclase activity of this fraction of mouse islets, although some remaining calmodulin [0.18 +/- 0.05 (n = 3) microgram/mg of protein] could be demonstrated. GTP (10 microM) enhanced islet adenylate cyclase activity considerably, but did not confer any sensitivity towards Ca2+-calmodulin on mouse islet adenylate cyclase. The results question the role of calmodulin in the Ca2+-dependent rise in cyclic AMP evoked by glucose in pancreatic islets.
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PMID:Differential effects of Ca2+-calmodulin on adenylate cyclase activity cyclase activity in mouse and rat pancreatic islets. 675 27

Basal adenylate cyclase activity in rat lung alveolar tissue particulate fraction was depressed during streptozotocin-induced diabetes. However, the activation of the particulate adenylate cyclase by the cytoplasmic factor(s) was markedly increased in lungs from the diabetic rats. The increased activation of basal adenylate cyclase in the diabetic tissue appeared to be due to an increase in the activity of the cytoplasmic factor(s) and not due to an increase in the sensitivity of the particulate enzyme to the cytoplasmic factor(s). Insulin treatment of the diabetic animals restored the activation of adenylate cyclase by the supernatant activator to the control values. The cytoplasmic factor(s) did not appear to be related to the ubiquitous calcium-dependent regulator protein, calmodulin.
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PMID:Influence of streptozotocin-induced diabetes on the cytoplasmic factors modulating adenylate cyclase activity in rat lungs. 702 48

The effects of several calmodulin antagonists on the antilipolytic activity of insulin were studied in isolated rat adipocytes. N-(6-aminohexyl)-5-Chloro-1-naphthalenesulfonamide (W-7) antagonized the inhibitory effect of insulin on lipolysis due to dibutyryl cyclic AMP (Bt2cAMP) (0.5 mM), but not due to adrenaline (1 microM) or 3-isobutyryl-1-methylxanthine (IBMX) (0.1 mM). The concentration of W-7 required for half-maximal suppression of antilipolytic effect of insulin (25 microU/ml) was 12 microM. High concentrations (up to 1000 microU/ml) of insulin could not overcome this suppression by W-7. W-7 did not affect the insulin binding to its receptor on fat cells. Other types of calmodulin antagonists such as trifluoperazine or calmidazolium did not antagonize the inhibitory effect of insulin. These findings show that the insulin receptor or calmodulin may not be involved in this suppressive effect of W-7.
Diabetes Res Clin Pract 1993 Mar
PMID:N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a calmodulin antagonist, reverses the inhibitory effect of insulin on lipolysis due to dibutyryl cyclic AMP. 768 56

Reduced expression of calmodulin (CaM) and decreased activity of low Km cyclic AMP (cAMP) phosphodiesterase (PDE) are associated with uncontrolled diabetes. This condition can be readily mimicked in hepatocytes cultivated in insulin-depleted medium (Solomon, et al J. Lab. Clin. Med. in press, 1994). To investigate the relationship between CaM and low Km cAMP PDE gene expression in response to insulin, we specifically blocked expression of the three CaM genes by antisense oligonucleotides under insulin-deficient and -sufficient conditions in a rat hepatoma cell line, H-411E. We observed that both the low Km cAMP PDE activity and the steady state levels of CaM mRNA were increased in response to insulin by 50 and 100%, respectively. When antisense oligonucleotide to CaM I, II or III was added to the cultures, only CaM I antisense oligonucleotide blocked insulin stimulation of both CaM I mRNA and protein with concommittant marked inhibition of insulin's expected stimulation of low Km cAMP PDE. Furthermore, in another experiment utilizing both antisense and oligonucleotide probes specific for CaM I, II, or III together, only CaM I mRNA expression was blocked. We conclude that H-411E cells respond to insulin by appropriate increases in CaM transcripts. Furthermore, the stimulatory effect of insulin on both CaM synthesis and activation of low Km cAMP PDE could be blocked by antisense to CaM I, but not II or III genes. Therefore, in addition to the above conclusions, H-411E hepatoma cells appear to be an excellent in vitro system to explore the molecular mechanisms by which CaM and low Km cAMP PDE genes are regulated in the diabetic state.
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PMID:Insulin-stimulated calmodulin gene expression in rat H-411E cells can be selectively blocked by antisense oligonucleotides. 776 64

Vanadate and vanadyl have been reported to have insulin-like properties and have recently been demonstrated to be beneficial in the treatment of diabetic animals. In this study, we determined whether vanadium ions mimic the effect of insulin on calmodulin activity of liver and adipose tissues in streptozotocin-induced diabetic rats and examined their effect with respect to concentration and time. Calmodulin activities in the hormone-sensitive tissues decreased in diabetes and returned to normal after sodium metavanadate or vanadyl sulfate treatment for 3 weeks (0.2, 0.4, and 0.8 mg/mL in drinking water). These results demonstrate that V5+ and V4+ forms of vanadium can restore the activity of calmodulin in experimental diabetes induced by streptozotocin.
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PMID:Effect of vanadium compounds on calmodulin activity in experimental diabetes in rats. 782 83

Red cell membrane cholesterol, 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[(4-trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) anisotropies and basal and calmodulin-stimulated calcium pump activities were compared in 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients and 20 normolipidaemic control subjects using the Mann-Whitney U-test. Serum cholesterol, membrane cholesterol, and membrane DPH and TMA-DPH anisotropies were similar in the two groups but both basal and calmodulin-stimulated calcium pump activities were reduced in the diabetic group: basal activity (median (inter-quartile range), mumol mg-1 h-1) 1.66 (1.18-1.97) vs 2.09 (1.90-2.50), p < 0.005 and calmodulin-stimulated activity 4.19 (3.07-5.48) vs 5.53 (4.70-6.88), p < 0.006. Although there were no correlations between glycaemic control and membrane anisotropy and between glycaemic control and calcium pump activity, the reduction in calcium pump activity is most likely due to a direct effect of diabetes on the calcium pump protein itself.
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PMID:Human red cell membrane fluidity and calcium pump activity in normolipidaemic type II diabetic subjects. 785 Oct 70


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