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)

Using prepubertal male New Zealand White rabbits, continuous subcutaneous insulin infusion (CSII), delivered by either an external or an implantable infusion device, resulted in significantly higher insulin antibody (I-Ab) production than bolus injection (BII). We tested the influence during CSII of (1) the insulin species, (2) the insulin diluent, (3) the materials of which the infusion devices were made and (4) the incubation of insulin in a syringe on the backs of rabbits ('sham-infusion'), with the following results: (1) beef and sulphated beef insulins produced high levels of I-Abs, while porcine and human insulins produced moderate levels; (2) with all insulins used, 0.9% NaCl and 0.9% NaCl with 24-26 mmol NaHCO3 added, produced high levels of I-Ab. A buffer containing 0.7% NaCl, 0.136% sodium acetate trihydrate and 0.1% methyl-p-hydroxybenzoate and a buffer containing 16 mg/ml glycerol and 2 mg/ml phenol, produced highly significantly lower I-Abs (P less than 0.001); (3) insulin glass syringes produced much lower I-Ab levels than in standard polypropylene syringes and (4) polypropylene syringes in a 'sham-infusion' technique, resulted in intermediate levels of insulin antibodies [(P less than 0.02) vs CSII; (P less than 0.005) vs BII]. Our data suggest that insulin immunogenicity is influenced by all four factors tested. We suggest that benefits of CSII therapy may be attenuated unless a best possible control of these factors is achieved.
Diabetes Res Clin Pract 1991 Apr
PMID:Continuous subcutaneous insulin infusion (CSII) and insulin antibodies in rabbits. 185 40

If ACE-inhibitors are considered for therapy in patients with heart failure, the actual renal function has to be taken into account. In patients with reduced intravascular volume, e.g. during therapy with diuretics, the renin-angiotensin system is activated. In this situation, the renin-angiotensin-system contributes to the maintenance of arterial blood pressure and glomerular filtration rate by angiotensin II mediated vasoconstriction in vas efferens and systemic circulation. A sudden complete inhibition of the renin-angiotensin system therefore may cause a pronounced decrease in blood pressure and a reduction in glomerular filtration rate (impaired renal excretory function). In patients with heart failure concomitant chronic renal failure, the use of ACE-inhibitors is without major risk; however, the clinical efficacy may be limited. This does not apply to patients with diabetes, where the risk for impairment of renal function is increased. The potential advantage of short acting ACE-inhibitors such as captopril may clinically be relevant only in patients with very advanced severe heart failure and low arterial pressure. In any case, it is recommended to start ACE-inhibitors with a low dose and withdraw diuretics one or two days before in order to restore the intravascular volume.
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PMID:[ACE inhibition in heart failure and compromised kidney function]. 186 34

Glucose metabolism in splenocytes from the BB rat was studied for the presence of abnormalities in [14C] 2-deoxy-D-glucose (2-dGlc) uptake, [U-14C]glucose conversion to 14CO2, and the production of lactate and pyruvate. Cells were studied freshly isolated ("resting"), and following culture both unstimulated (control) and stimulated with concanavalin A (ConA) or phorbol myristate acetate (PMA) + ionomycin. Both resting and control cells from diabetic (BBd) and diabetes-prone (BBdp) rats transported more (p less than 0.05) 2-dGlc than did cells from nondiabetes-prone (BBn) rats. Consistent with prior in vivo activation, sustained in vitro, lactate production was higher (p less than 0.05) under control conditions in BBd and BBdp than in BBn cells. Lactate production increased less with ConA and PMA + ionomycin in both BBd and BBdp than in BBn cells. PMA + ionomycin increased 2-dGlc uptake as much in BBd and BBdp cells as in BBn cells. Elevated rates of pyruvate production were observed in BBd cells under resting, control, and (especially) ConA conditions, suggesting an abnormality in pyruvate conversion to lactate. Few changes were observed in 14CO2 production. The presence of similar abnormalities in BBdp cells to those of the BBd cells suggests that the diabetic state is not causal, and the absence of an in vitro effect of 15 mmol/liter glucose in BBn cells further tends to exclude hyperglycemia as a cause of these alterations.
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PMID:Enhanced 2-deoxy-D-glucose uptake and metabolism in splenocytes from diabetic and diabetes-prone BB rats. Further evidence to support prior in vivo activation. 189 65

Captopril (CAS 62571-86-2) may be beneficial for the treatment of diabetes because of its activating effect on peripheral glucose consumption besides its well known blood pressure degradation. The glucose oxidation has been found to be activated by captopril in thrombocytes and mononuclear leucocytes, cell types which are usually considered to be independent from insulin. Because the oxidation of pyruvate labelled in position C-1 but not of 2-14C-pyruvate and of 1-14C-acetate was enhanced, captopril most probably stimulated the pyruvate decarboxylation reaction. The metabolism of glucose labelled in positions 1 and 6 was equally activated by captopril indicating another step which may be affected by captopril.
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PMID:Influence of captopril on glucose and fatty acid oxidation in human thrombocytes and mononuclear leucocytes. 190 26

The effect of Ca2+ and calmodulin on phosphorylation of islet secretory granule proteins was studied. Secretory granules were incubated in a phosphorylation reaction mixture containing [32P]ATP and test reagents. The 32P-labeled proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the 32P content was visualized by autoradiography, and the relative intensities of specific bands were quantitated. When the reaction mixture contained EGTA and no added Ca2+, 32P was incorporated into two proteins with molecular weights of 45,000 and 13,000. When 10(-4) M Ca2+ was added without EGTA, two additional proteins (58,000 and 48,000 Mr) were phosphorylated, and the 13,000-Mr protein was absent. The addition of 2.4 microM calmodulin markedly enhanced the phosphorylation of the 58,000- and 48,000-Mr proteins and resulted in the phosphorylation of a major protein whose molecular weight (64,000 Mr) is identical to that of one of the calmodulin binding proteins located on the granule surface. Calmodulin had no effect on phosphorylation in the absence of Ca2+ but was effective in the presence of calcium between 10 nM and 50 microM. Trifluoperazine and calmidazolium, calmodulin antagonists, produced a dose-dependent inhibition of the calmodulin effect. 12-O-tetradecanoylphorbol 13-acetate, a phorbol ester that activates protein kinase C, produced no increase in phosphorylation, and 1-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride, an inhibitor of protein kinase C, had no effect. These results indicate that Ca(2+)-calmodulin-dependent protein kinases and endogenous substrates are present in islet secretory granules.
Diabetes 1991 Aug
PMID:Ca(2+)-calmodulin-dependent phosphorylation of islet secretory granule proteins. 190 48

Carbonic anhydrase (CA) is a well characterized pH regulatory enzyme in most of the tissues in the body. Changes in activities of CA have been associated with altered metabolism, especially in diabetes mellitus. Insulin resistance and hyperinsulinemia are common in hypertension. To investigate the possible role of CA, we measured the CA activity spectrophotometrically using p-nitrophenyl acetate as a substrate and acetazolamide, the specific inhibitor, in erythrocytes from normotensive and essential hypertensive subjects. Further, to evaluate the insulin action on CA, we used two different hemolysates; (i) insulin applied into hemolysate and (ii) hemolysate from insulin treated erythrocytes in vitro before the determination of CA activity. Two different levels of CA activities were obtained in these patients. CA activities were much lower (mean +/- SD, 0.88 +/- 0.19 U/min/mL) and higher (mean +/- SD, 1.77 +/- 0.23 U/min/mL) in patients than the normotensive controls (mean +/- 1 SD, 1.41 +/- 0.1 U/min/mL). These differences in both the groups were statistically significant (p less than 0.001). Similarly, total esterase activities in patients were (1.41 +/- 0.27 U/min/mL) that was 30% less in low activity group and (2.47 +/- 0.25 U/min/mL) that was 22% more in higher activity group in comparison with those from normotensives (2.02 +/- 0.17 U/min/mL). The relative percent of CA activities of insulin treated erythrocytes from normotensives and hypertensives were 11% and 18% higher than without insulin (p less than 0.05). No difference was observed when insulin was applied in the hemolysate. We conclude that essential hypertensive patients are associated with altered CA activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in carbonic anhydrase may be the initial step of altered metabolism in hypertension. 190 43

To study platelet activation as a phenomenon that may precede development of angiopathy in diabetes mellitus, we compared platelet adhesion and thrombus formation in a flow system with blood from insulin-dependent (type I) diabetic subjects with and without macroangiopathy and age- and sex-matched control subjects. Adhesion and thrombus formation on matrix of cultured human endothelial cells (ECM) and adhesion on matrix of human fibroblasts (FBM) were studied after exposure to flowing blood at shear rates of 300 and 1300 s-1 and exposure times of 1, 3, 5, and 10 min (and 20 min in adhesion experiments). Blood was anticoagulated with trisodium citrate (1:10 vol/vol, 110 mM) or low-molecular-weight heparin ([LMWH] 20 U/ml). Endothelial cell cultures were either unstimulated or stimulated with 4 beta-phorbol 12-myristate 13-acetate (PMA) 16 h before isolating their matrix. Platelet adhesion on ECM and FBM in citrated and LMWH-anticoagulated blood was identical in diabetic patients and control subjects, with comparable increases of adhesion with increasing perfusion times. Platelet aggregate formation on ECM of PMA-stimulated cells with LMWH-anticoagulated blood was similar in diabetic patients, whether macroangiopathy was present, compared with control subjects. Fibrin deposition and fibrinopeptide A generation during perfusion were comparable in diabetic and control subjects. Platelet thromboxane B2 formation after stimulation with arachidonic acid was increased in diabetic patients without macroangiopathy compared with age- and sex-matched control subjects. In the perfusion system, the patterns of platelet adhesion and aggregate formation on extracellular matrix in flowing blood of diabetic patients (with or without macroangiopathy), and healthy age- and sex-matched control subjects followed a similar pattern.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Nov
PMID:Platelet adhesion and aggregate formation in type I diabetes under flow conditions. 193 2

To study the mechanism of action of sulfonylurea agents on peripheral tissues without the potentially confounding influences of insulin, the direct effect of glyburide (i.e., in the absence of insulin) was evaluated in the L6 cultured myogenic cell line. Glyburide approximately doubled the incorporation of [14C]-glucose into glycogen. The rate-determining enzymes of glycogen metabolism, glycogen synthase and glycogen phosphorylase, were unaffected by the drug. Glucose transport (2-deoxyglucose uptake) was also approximately doubled. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) also doubled glucose transport and showed the same lag period (4-6 h) as glyburide before an effect occurred. Blockade of protein kinase C activity by either 1-(5-isoquinolinesulfonyl)-2 methyl piperazine (H7) or chronic exposure to TPA completely abolished the stimulation by glyburide. Cycloheximide, a protein synthesis inhibitor, also completely eliminated the effect of glyburide. The presence of ATP-sensitive K+ channels was assessed by measuring 86Rb efflux in ATP-depleted L6 muscle cells and RINm5F cells (which served as a positive control). Such channels were present and responded appropriately to glyburide and diazoxide in pancreatic beta-cells but were not present in muscle cells. Glyburide stimulation of glucose transport was completely eliminated by both Quin 2, an intracellular chelator of Ca2+, and verapamil, a Ca2+ channel blocker. However, glyburide did not raise intracellular Ca2+ levels. We conclude that glyburide stimulates glucose transport in cultured L6 muscle cells by a protein kinase C-mediated pathway that requires new protein synthesis. Although intracellular Ca2+ metabolism may also be involved, the initial step in the mechanism of action is probably different between pancreatic beta-cells and muscle cells.
Diabetes 1991 Nov
PMID:Glyburide-stimulated glucose transport in cultured muscle cells via protein kinase C-mediated pathway requiring new protein synthesis. 193 11

Hemoglobin A1c was studied by means of isoelectric focusing in borate-polyol system and modified albumin--using electrophoresis of blood serum on acetate-cellulose films with subsequent TCA-ethanol sedimentation in healthy volunteers and patients with diabetes mellitus. These parameters were increased in the patients, whereas content of the albumin was decreased and the content of hemoglobin A1c was altered only slightly during treatment of diabetes. Content of hemoglobin A1c and modified albumin was shown to depend on the compensation state of diabetes mellitus.
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PMID:[Level of hemoglobin A1c and modified blood serum albumin in patients with diabetes mellitus]. 194 83

Unseparated splenocytes (SPCs) or purified SPC subsets from diabetes-prone BB (BBdp) or diabetic BB (BBd) rats were activated in vitro with either phorbol myristate acetate (PMA) and ionomycin (I) or concanavalin A (ConA). Such activated SPCs were then injected intravenously into 30-day-old BBdp rats, and their capacity to induce adoptive transfer (AT) of diabetes was studied. The proliferative response in vitro of BBd unseparated SPCs or purified W3/13+ SPCs (i.e., T lymphocytes + large granular lymphocytes) to PMA + I far exceeded that of ConA, resulting in mean stimulation indices of 68 and 112 (PMA + I) and 1.9 and 30 (ConA). The incidence of AT was similar when equal numbers of unseparated SPCs from the same BBd donor were injected after activation by either PMA + I + interleukin 2 (PII) or ConA (57 vs. 50%, respectively); however, injection of PII-activated and macrophage-depleted W3/13+ SPCs from BBd animals resulted in a significantly higher incidence of AT (90%, P less than 0.05). As few as 0.5 x 10(6) PII-activated W3/13+ SPCs were sufficient to induce AT. Sixteen percent of recipients developed diabetes after injection of activated W3/13+ cells from 40-day-old BBdp donors. To determine which W3/13+ cells might mediate such transfer, purified and PII-preactivated CD4 T lymphocytes from BBd rats were injected, and they succeeded in AT in 44% of the recipients. Preactivated BBd B lymphocytes were unable to induce AT. Although a possible role for large granular lymphocytes cannot be excluded, the results demonstrate that in the BB rat, the beta-cell destruction can be induced by CD4 T lymphocytes.
Diabetes 1990 Aug
PMID:Adoptive transfer of diabetes in BB rats induced by CD4 T lymphocytes. 197 71


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