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)

Content of chemical elements (CE) in washed out erythrocytes was studied by nuclear-absorptive spectroscopy in 26 patients with insulin-dependent diabetes mellitus (IDDM), 26 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 29 healthy subjects. It was established that erythrocytes in IDDM contain significantly less amounts of cuprum, manganese and cobalt than in healthy subjects, content of zinc being increased. Contents of iron, cuprum, manganese and zinc were found to be decreased in patients with NIDDM as compared to the control. During the conventional treatment erythrocytes of patients with IDDM revealed increase of cuprum content while in NIDDM rise in amounts of iron, manganese, cobalt and zinc was observed. Changes of erythrocytes CE content in diabetes mellitus are supposed to be of compensatory-adaptive nature, for decompensation of IDDM and NIDDM is associated with more pronounced CE dysbalance. Increased erythrocyte content of zinc in IDDM may be explained by uptake of prolonged insulin used for substituting treatment.
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PMID:[Disordered trace element content of the erythrocytes in diabetes mellitus]. 806 18

To study the effect of vanadium (V) intake on blood glucose lowering, tissue V concentrations, glutathione reductase (GR) activity, and plasma trace metal concentrations, streptozotocin(STZ)-diabetic rats were treated with vanadyl sulfate (VS) (0.5-1.2 g/l in the drinking water) for up to 12 weeks. Kidney and plasma V concentrations were positively correlated with V intake. Kidney GR activities were not affected by VS treatment nor were plasma cobalt, molybdenum, manganese or lithium concentrations. Individual V intakes were dependent upon severity of diabetes, with more hyperglycemic rats consuming greater quantities of VS solution. A diminished effect on glucose lowering of VS above 1 g/l was noted.
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PMID:Studies of vanadyl sulfate as a glucose-lowering agent in STZ-diabetic rats. 828 Jan 74

The insulin hexamer has two high-affinity metal ion binding sites, each involving three HisB10 residues, one from each dimer. Insulin hexamers containing Co2+ at both these sites were oxidized to form a stable Co(3+)-insulin complex. It is shown that the Co(3+)-coordinated insulin monomers are released extremely slowly in aqueous solution at pH 8.0, and that the hexamer does not spontaneously dissociate into subunits at nanomolar concentrations of insulin. The Co(3+)-insulin hexamer is not recognized by the insulin receptor in vitro but the complex shows a protracted action profile following subcutaneous (s.c.) injection into rabbits. The Co(3+)-insulin hexamer provides a novel prodrug approach to a soluble, prolonged-acting insulin preparation of potential use for basal insulin delivery in the treatment of diabetes.
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PMID:The cobalt(III)-insulin hexamer is a prolonged-acting insulin prodrug. 880 29

Vanadium and its compounds exhibit a wide variety of insulin-like effects. In this review, these effects are discussed with respect to the treatment of type I and type II diabetes in animal models, in vitro actions, antineoplastic role, treatment of IDDM and NIDDM patients, toxicity, and the possible mechanism(s) involved. Newly established CytPTK plays a major role in the bioresponses of vanadium. It has a molecular weight of approximately 53 kDa and is active in the presence of Co2+ rather than Mn2+. Among the protein-tyrosine kinase blockers, staurosporine is found to be a potent inhibitor of CytPTK but a poor inhibitor of InsRTK. Vanadium inhibits PTPase activity, and this in turn enhances the activity of protein tyrosine kinases. Our data show that inhibition of PTPase and protein tyrosine kinase activation has a major role in the therapeutic efficacy of vanadium in treating diabetes mellitus.
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PMID:Vanadium salts as insulin substitutes: mechanisms of action, a scientific and therapeutic tool in diabetes mellitus research. 899 1

The charts of 319 consecutive patients who underwent total laryngectomy at the Cancer Institute Hospital from 1971 to 1994 were reviewed in order to clarify the relationship between pharyngo-cutaneous fistula formation and age, the dose of pre-operative radiation and radical neck dissection, as well as the need for subsequent surgical repair. The patients did not need to undergo reconstruction by flaps at the time of laryngectomy. Radiation sources were limited to X ray radiotherapy and Cobalt 60. Of the 319 patients 204 (63.9%) underwent neck dissection. Both radical neck dissection and modified radical neck dissection were classified as neck dissection. The chi-square test was used to construct a table of the three parameters age, dose of radiation and neck dissection. With respect to age, the incidence of fistula formation was 13.4% (16 patients of 119) in patients at the age of 59 and below, 5.9% (7/118) in those from 60 to 69, and 8.5% (7/82) in those at 70 years and above. Our analysis reveals that the age at the time of surgery is not a predisposing factor for fistula formation in the three age groups (59 and below, between 60 and 69, and 70 and above). Similarly the need for subsequent surgical repair is also not age-related. With respect to radiation, the incidence of fistula formation was 8.0% (4/50) for patients who received radiotherapy less than 20 Gy, 6.3% (2/32) in those who received between 20 and 40 Gy, 2.6% (2/77) in those who received between 40 and 60 Gy, 13.2% (20/152) in those who received between 60 and 80 Gy and 25.0% (2/8) in those who received over 80 Gy. When the preoperative dose of radiation was divided into three classes, that is, less than 40 Gy, 40 to 60 Gy and over 60 Gy, we observed that the incidence of fistula formation increased significantly in the patients who received over 60 Gy. Surgical repair was also indicated more frequently for those patients who received over 60 Gy than for those who received less than 60 Gy. With respect to neck dissection, the incidence of fistula formation was 12.2% (14/115) for the patients who did not undergo neck dissection or those who underwent only lymphadenectomy, 7.8% (9/115) for the patients who underwent unilateral neck dissection, and 7.9% (7/89) for those who underwent bilateral neck dissection. These data reveal that neck dissection, whether unilateral or bilateral, dose not increase the incidence of fistula formation, nor the need for subsequent surgical repair. Fistulae were present in 30 patients (9.4%) for 24 years, and 14 of these 30 patients did not need subsequent surgery. In these 30 patients with fistulae, we did not find patients with systemic disease such as diabetes mellitus prior to the surgery. When the period of 24 years was divided into 4 periods, the incidence of fistula formation was 19.0% (from 1971 to 1976), 6.9% (from 1977 to 1982), 10.3% (from 1983 to 1989) and 2.6% (from 1989 to 1994), that of the latest period was the lowest with gradual improvement. The average dose of preoperative radiation was 57.7 Gy (from 1971 to 1976), 50.8 Gy (from 1977 to 1982), 39.6 Gy (from 1982 to 1988) and 45.7 Gy (from 1989 to 1994) and reduction in dose of radiation seemed to be one of the reasons for the lower frequency of fistula. Several surgeons performed the operations for different patients, but the procedure of laryngectomy was recently directed by an experienced surgeon. The study also indicates that the risk of fistula formation is reduced not only by the dose of radiation but also by improved surgical skill.
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PMID:[Pharyngo-cutaneous fistula after total laryngectomy]. 907 Nov 21

There is a continuing search for improved insulin formulations in order to imitate as closely as possible the physiological pattern of insulin secretion, and thereby to minimise the complications of diabetes mellitus. The major advances achieved to date are in the area of human insulin analogue synthesis resulting from the introduction of recombinant DNA techniques, and in improved delivery systems that utilise noninvasive or minimally invasive modes of administration. To accommodate postprandial hyperglycaemia, monomeric insulin formulations have been developed, of which insulin lispro (the Lys-Pro analogue) is already approved for clinical use. These formulations have a rapid rate of absorption and, therefore, have to be administered at meal time (unlike the previous short-acting formulations). Their residence time is also about 2-fold shorter than regular human insulin; this minimises the risk of the excessive hypoglycaemic effect that characterises regular human insulin formulations. Certain proinsulin formulations with hepatoselective activity have been developed but were found to be poorly tolerated. The newer proinsulin molecules do not show hepato-selective properties. In order to generate basal insulin levels, peakless long-acting formulations have been developed, including: a soluble formulation (which upon subcutaneous administration, produces a 'depot-like' sustained release mechanism), albumin-bound insulin and cobalt-insulin hexamer formulations. To improve patient compliance the 'pen' device was developed for subcutaneous injections. Programmable infusion pumps were developed to avoid repetitive subcutaneous injections. Great efforts have been made in searching for noninvasive modes of insulin administration that will avoid the need for parenteral administration. These include: oral, colonic, rectal, nasal, ocular, buccal, pulmonary, uterine and transdermal routes of administration. Various enhancers have been tested to increase the bioavailability of each route. At present these alternative routes do not provide clinically relevant substitutes for the subcutaneous mode of administration. In conclusion, although the newer formulations provide certain advantages, there is still much to be done to further facilitate and improve insulin therapy.
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PMID:Pharmacokinetic considerations of new insulin formulations and routes of administration. 934 4

Acromegaly was diagnosed in 3 cats with insulin-resistant diabetes mellitus (DM) on the basis of history and physical examination findings, which ruled out other causes of insulin-resistant DM, and by documenting high plasma concentrations of growth hormone. Computed tomography revealed a mass in the area of the pituitary gland in each cat. Pituitary gland tumors were irradiated with cobalt 60, and none of the cats developed complications to radiotherapy. Each cat received a total dose of 48 Gy of cobalt 60 during 12 treatments. After completion of radiotherapy, insulin requirements were less for all cats, although in 1 cat, this improvement was transient. Diabetes mellitus resolved in 2 of 3 cats. After treatment, decreases in insulin requirements correlated with decreases in plasma growth hormone concentrations in 2 of 3 cats in which DM resolved. On the basis of these findings, irradiation of pituitary gland tumors appears to be a treatment option for cats with acromegaly.
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PMID:Cobalt 60 irradiation of pituitary gland tumors in three cats with acromegaly. 970 26

Orbital radiotherapy is a well-established method of treatment for severe Graves' ophthalmopathy, because of its anti-inflammatory and locally immunosuppressive effects. It has been used for 60 years. Conventional external x-ray and cobalt therapy have been abandoned, and most groups now use supervoltage linear accelerators (4-6 MeV). Cumulative doses may vary, but in most studies a cumulative dose of 20 Gy delivered over 2 weeks was utilized. Successful outcome depends on the selection of patients, because recent onset, active ophthalmopathy is much more favorably affected than longstanding, inactive disease. Inflammatory signs, recent onset eye muscle dysfunction, and optic neuropathy respond well to orbital radiotherapy, while proptosis and longstanding eye muscle restriction respond poorly. Overall, favorable responses have been reported, with few exceptions, in approximately 60% of cases. Combination of irradiation with high-dose systemic glucocorticoids provides better results than either treatment alone. Orbital radiotherapy is well tolerated and safe. Preexisting retinopathy (e.g., in patients with diabetes) is a contraindication to this treatment for the risk of further retinal damage. No case of radiation-induced tumors has so far been described after orbital radiotherapy for Graves' ophthalmopathy.
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PMID:Orbital radiotherapy for Graves' ophthalmopathy. 1195 48

The synthesis and characterization of Co(II) and Co(III) 2,6-pyridinedicarboxylate (dipic(2-)) complexes are reported. Solid-state X-ray characterizations were performed on [Co(H(2)dipic)(dipic)].3H(2)O and [Co(dipic)(mu-dipic)Co(H(2)O)(5)].2H(2)O. Two coordination modes not previously observed in dipicolinate transition metal complexes were observed in these complexes; one involves metal coordination to the short C-O (C=O) bond, and the other involves metal coordination to a protonated oxygen atom. Solution studies, including paramagnetic NMR and UV-vis spectroscopy, were done showing the high stability and low lability of the Co(III) complex, whereas the Co(II) complexes exhibited ligand exchange in the presence of excess ligand. The [Co(dipic)(2)](2-) complex has pH dependent lability and in this regard is most similar to the [VO(2)dipic](-) complex. The [Co(dipic)(2)](2-) was found to be effective in reducing the hyperlipidemia of diabetes using oral administration in drinking water in rats with STZ-induced diabetes. Oral administration of VOSO(4) was used as a positive control for metal efficacy against diabetes. In addition to providing a framework to evaluate structure-function relationships of various transition metal complexes in alleviating the symptoms of diabetes, this work describes novel aspects of structural and solution cobalt chemistry.
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PMID:Cobalt(II) and cobalt(III) dipicolinate complexes: solid state, solution, and in vivo insulin-like properties. 1223 Mar 90

Effects of cobalt on the antioxidant status of control and streptozotocin diabetic rat heart and aorta were examined at the second, fourth and sixth week of treatment. Rats were divided into four groups: control, diabetic, control treated with cobalt chloride and diabetic treated with cobalt chloride. Diabetes was induced by tail vein injection of streptozotocin (STZ). Cobalt treatment groups were given 0.5 mM of CoCl(2) in drinking water. The rats in both groups were further subdivided into three groups of six rats each. Rats in these subgroups were studied at 2-week intervals up to 6 weeks. At the end of the experiment, all animals were sacrificed by decapitation, heart and aorta samples were removed for determination of thiobarbituric acid reactive substance (TBARS) level and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. It was found that lipid peroxidation levels and antioxidant enzyme activities were increased in the streptozotocin-induced diabetic rats at all times studied. Cobalt treatment of diabetic rats (0.5 mM in drinking water) resulted in attenuation of the increased levels of TBARS and antioxidant enzyme activities in heart and aorta. Thus, the effect of oral administration of cobalt at this dose during the early stage of experimental diabetes can be considered as a consequence of altered endogenous defence mechanisms in heart and aorta.
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PMID:Effect of cobalt on the oxidative status in heart and aorta of streptozotocin-induced diabetic rats. 1257 18


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