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)

Insulin resistance is found patients with diabetes mellitus type 2 as well as in obese subject without diabetes. The objective of our investigation was to compare the action of insulin in morbidly obese subject with and without diabetes and in diabetic subject with different degrees of obesity. A total of 36 diabetic were examined, divided according to the BMI into morbidly obese (DMTO: BMI > 40 kg/m-2.n = 6) those with medium severe obesity (DMSO: BMI 31-40 kg.m-2.n = 16), with slight overweight DMLO. BMI 26-91 kg.m-2.n = 9) and non-obese diabetics (DMBO). BMI 21-26 kg.m-2.n = 5). The group of morbidly obese non-diabetic subject (NDTO, BMI > 40 kg.m-2.n = 5) and non-obese healthy subject (C, BMI < 26 kg.m-2, n = 12) served as control. All examined subject were of similar age the diabetic subject had similar values of indicator of diabetic control (HbA1c was 7.1 +/- 0.5%). The examination was made using the method of an isoglycaemic hyperinsulinaemic clamp on a Biostator at an insulin infusion rate of 1mU.kg-1.min-1 for a period of 20 minutes. The results of the index of tissue sensitivity to insulin revealed a markedly deteriorated action of insulin in morbidly obese diabetes and non-diabetics in relation to control group of healthy slim controls (M/I, DMTO: 12.4 +/- 7.3 and NDTO: 9.2 +/- 4.1, p < 0.001, mumol.kg-1.min-1 na mU.l-1 x 100), in midly and medium obese diabetics the insulin resistance was of difference grades (M/I, DMLO: 34.2 +/- 9.3, p < 0.05, and DMSO: 25.9 +/- 18.5 p < 0.001 mumol.kg-1.min-1 na mU.l-1 x 100. Non-obese diabetic and non-diabetic subject had a normal insulin action (M/I, DMBO: 58.3 +/- 29.4 and C: 48.9 +/- 5.0 mumol.kg-1.min-1 per mU.l-1 x 100. The metabolic glucose clearance differed however between diabetic and non-diabetic subject (MCRG, DMTO: 2.0 +/- 0.4, p < 0.001, DMSO: 3.8 +/- 2.4, p < 0.001, DMSO: 5.4 +/- 1.7, p < 0.05 v.s. C: 8.6 +/- 1.1 and NDTO: 3.8 +/- 1.5, p < 0.001 ml.kg-1.min-1). The statistical significance is related to the control group of slim healthy subject. From this ensues that no significant difference was found between slim diabetic and non-diabetic subjects in the majority of parameters expressing the action of insulin with the exception of the metabolic glucose clearance. At the same time the authors found in the whole group of 53 examined subject a statistically significant correlation between the BMI and the index of tissue sensitivity for insulin (M/I) (r = -0.55, p < 0.001). On examination of characteristics of insulin receptors on erythrocytes the authors found a reduced number in diabetic subject as compared with the two control groups (p < 0.05). It may thus be concluded from this investigation that the BMI has a decisive role in the action insulin.
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PMID:[The effect of body weight on insulin activity]. 1095 79

Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Experimental evidence suggests that a defect in vascular endothelial growth factor (VEGF) regulation might be associated with wound-healing disorders. We studied the involvement of lipid peroxidation in the pathogenesis of altered VEGF expression in diabetes-related healing deficit by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ db+/ db+ mice and their normal (db+/+m) littermates. Animals were then randomized to the following treatment: raxofelast (15 mg.kg(-1).day(-1) i.p.), an inhibitor of lipid peroxidation, or its vehicle (DMSO/NaCl 0.9%, 1:1 vol: vol). The animals were killed on different days (3, 6, and 12 days after skin injury), and the wounded skin tissues were used for histological evaluation, for analysis of conjugated dienes (CDs), as an index of lipid peroxidation and wound breaking strength. Furthermore, we studied the time course of VEGF mRNA expression throughout the skin-repair process (3, 6, and 12 days after skin injury), by means of reverse transcriptase-polymerase chain reaction, as well as the mature protein in the wounds. Diabetic mice showed impaired wound healing with delayed angiogenesis, low breaking strength, and increased wound CD content when compared with their normal littermates. In healthy control mice, a strong induction of VEGF mRNA was found between day 3 and day 6 after injury, while no significant VEGF mRNA expression was observed at day 12 after injury. In contrast, VEGF mRNA levels, after an initial increase (day 3), were significantly lower in diabetic mice than in normal littermates, and light induction of VEGF mRNA expression was also present at day 12 after injury. Similarly, the wound content of the angiogenic factor was markedly changed in diabetic mice. Administration of raxofelast did not modify the process of wound repair in normal mice, but significantly improved the impaired wound healing in diabetic mice through the stimulation of angiogenesis, re-epithelization, and synthesis and maturation of extracellular matrix. Moreover, raxofelast treatment significantly reduced wound CD levels and increased the breaking strength of the wound. Lastly, the inhibition of lipid peroxidation restored the defect in VEGF expression during the process of skin repair in diabetic mice and normalized the VEGF wound content. The current study provides evidence that lipid peroxidation inhibition restores wound healing to nearly normal levels in experimental diabetes-impaired wounds and normalizes the defect in VEGF regulation associated with diabetes-induced skin-repair disorders.
Diabetes 2001 Mar
PMID:Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse. 1124 89

This article presents and evaluates the symptoms, presentation, diagnosis, and treatment of men with interstitial cystitis (IC). A retrospective chart review and an interview of all men in our practice diagnosed with IC since 1990 was performed. The patients' presenting symptoms, physical findings, clinical evaluation, and responses to therapy were reviewed. A total of 52 men were identified during the study who met the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria for diagnosis of IC. The most common referral diagnosis was prostatitis with the most common predominant symptoms being suprapubic pain with urinary frequency and dysuria. A significant number of male patients also developed sexual dysfunction. All patients met the NIDDK criteria for a diagnosis of IC. Multiple therapies were used for the treatment of these patients over the study period. Five patients were initially treated with dimethyl sulfoxide (DMSO) as a sole agent; however, all intravesically treated patients eventually failed this form of therapy. A total of 37 of 52 patients were treated with multidrug oral therapy. Findings showed that 80% of patients achieved >75% improvement in their symptomology at 6 months of follow-up with a durable response at 1 year. IC in men is probably underdiagnosed and is most commonly misdiagnosed as prostatitis. The patient's presentation is analogous to that in the female population allowing for gender differences. The patients responded well to multidrug oral therapy.
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PMID:Observations on the presentation, diagnosis, and treatment of interstitial cystitis in men. 1137 46

Because the role of elemental sulfur in human nutrition has not been studied extensively, it is the purpose of this article to emphasize the importance of this element in humans and discuss the therapeutic applications of sulfur compounds in medicine. Sulfur is the sixth most abundant macromineral in breast milk and the third most abundant mineral based on percentage of total body weight. The sulfur-containing amino acids (SAAs) are methionine, cysteine, cystine, homocysteine, homocystine, and taurine. Dietary SAA analysis and protein supplementation may be indicated for vegan athletes, children, or patients with HIV, because of an increased risk for SAA deficiency in these groups. Methylsulfonylmethane (MSM), a volatile component in the sulfur cycle, is another source of sulfur found in the human diet. Increases in serum sulfate may explain some of the therapeutic effects of MSM, DMSO, and glucosamine sulfate. Organic sulfur, as SAAs, can be used to increase synthesis of S-adenosylmethionine (SAMe), glutathione (GSH), taurine, and N-acetylcysteine (NAC). MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders. Other sulfur compounds such as SAMe, dimethylsulfoxide (DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical applications in the treatment of a number of conditions such as depression, fibromyalgia, arthritis, interstitial cystitis, athletic injuries, congestive heart failure, diabetes, cancer, and AIDS. Dosages, mechanisms of action, and rationales for use are discussed. The low toxicological profiles of these sulfur compounds, combined with promising therapeutic effects, warrant continued human clinical trails.
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PMID:Sulfur in human nutrition and applications in medicine. 1189 44

Exenatide, synthetic exendin-4, is the first member of the incretin mimetic class of potential therapeutic agents. It has been the subject of extensive clinical trials in people with Type 2 diabetes. Results to date indicate that exenatide decreases postmeal blood glucose concentrations and that this effect is associated with weight loss. Prior NMR studies of exendin-4 utilized 30% trifluoroethanol because this medium affords sharp, high-resolution NMR spectra. These studies defined its three-dimensional structure in this medium. The NMR-derived ensemble included a novel tertiary structure motif that has subsequently been optimized, yielding water-soluble Trp-cage miniproteins. Prior to the present study, the structuring propensities (and aggregation/association state) of exendin-4 in strictly aqueous media had not been established. Studies of exendin-4 and N-terminally truncated analogs of exendin have established that the structuring propensities of these species are highly medium dependent. This study extends knowledge of the medium dependence of exendin structure to DMSO-water mixtures and to aqueous media mimicking the formulation conditions for this investigational drug. Exenatide retains a substantial helical propensity from residues 9-27 even in 98% DMSO. The addition of water leads to the appearance of NMR diagnostics of the Trp-cage formation. In strictly aqueous media (pH 4-4.4), exenatide is monomeric only at <10 microM peptide concentrations. Under these conditions the Trp cage is partially formed. NMR and CD data indicate that higher concentrations lead to helix bundle formation and that the helix/helix interactions involve residues 11-26. Both the N- and C-termini of the helix bundle state display rapid segmental motion.
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PMID:Exenatide: NMR/CD evaluation of the medium dependence of conformation and aggregation state. 1538 69

A 40-year-old man presented with hardening of the skin of his hands and upper back, which had slowly worsened with time. His medical history included insulin-dependent diabetes mellitus since childhood. Histopathologic features of a biopsy specimen from the skin of his back showed a thick reticular dermis with collagen bundles in a haphazard array, which were separated by increased deposits of connective-tissue mucin. Scleredema and diabetic sclerodactyly are both well recognized skin findings that may occur in patients with diabetes mellitus. It is important to differentiate this condition from scleroderma. Treatment is difficult, and therefore many modalities have been used. This patient has improved with aminobenzoate, colchicine, and DMSO gel.
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PMID:Scleredema and diabetic sclerodactyly. 1640 75

Oxidative stress is currently hypothesized to be a mechanism underlying diabetes. The present study was designed to evaluate the effect of umbelliferone (UMB), a derivative of coumarin, on erythrocyte lipid peroxidation, antioxidants, and lipid profile in normal and streptozotocin (STZ) diabetic rats. Diabetes was induced in adult male albino rats of Wistar strain, weighing 180 to 200 g, by the administration of STZ (40 mg/kg/b-wt) intraperitonially. The normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) dissolved in water for 45 days. The diabetic rats had elevated levels of blood glucose and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxide (HP) and decreased levels of nonenzymatic antioxidants (Vitamin C and reduced glutathione [GSH]), elevated levels of vitamin E, and elevated levels of enzymatic antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), elevated glucose-6-phosphate dehydrogenase activity, and altered lipid profile (cholesterol and phospholipids) in erythrocytes. These changes were reversed by treatment with UMB. Thus, our results indicate that the administration of UMB shows promising potential for the restoration of normal blood glucose levels, erythrocyte lipid peroxidation, antioxidants, and lipid profile in STZ-diabetic.
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PMID:Impact of umbelliferone on erythrocyte redox status in STZ-diabetic rats. 1646 11

The objective of the study was to investigate the role of Umbelliferone (UMB) on lipid peroxidation, nonenzymic and enzymic antioxidants in the plasma and liver of streptozotocin (STZ)-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180-200 g, were induced diabetes by administration of STZ (40 mg/kg b.wt.) intraperitoneally. The normal and diabetic rats were treated with UMB (30 mg/kg b.wt.) dissolved in 10% dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had an elevation in the levels of lipid peroxidation markers (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD)), and a reduction in nonenzymic antioxidants (vitamin C and reduced glutathione (GSH) except vitamin E in the plasma and liver, and enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the liver. Decreased level of beta-carotene and increased level of ceruloplasmin (Cp) were observed in the plasma of diabetic rats. Treatment with UMB and glibenclamide brought back lipid peroxidation markers, nonenzymic and enzymic antioxidants to near normalcy. Since UMB treatment decreases lipid peroxidation markers and enhances antioxidants' status it can be considered as a potent antioxidant.
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PMID:Antioxidant role of Umbelliferone in STZ-diabetic rats. 1646 72

The aim of the study was to evaluate blood glucose and lipid lowering effects of Umbelliferone (UMB) in streptozotocin (STZ) diabetic rats. Male albino Wistar rats (180 to 200 g) were induced diabetes by administration of STZ (40 mg/kg) intraperitonially. Normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) for 45 days. Diabetic rats had increased plasma glucose and decreased insulin, total proteins (TP), and albumin in addition to decreased food intake and body weight. Elevation in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL), and reduction in high density lipoprotein cholesterol (HDL-C) in the plasma were observed. Liver and kidney tissues of diabetic rats had elevation in the levels of TC, TG, FFA, and PL. Treatment with UMB decreased plasma glucose and increased insulin, TP, and albumin apart from food intake and body weight. In UMB-treated diabetic rats, plasma and tissue TC, TG, PL and FFA, and plasma LDL-C, VLDL-C, and HDL-C reversed to near normal. Thus, reduction of blood glucose and lipid profiles indicates that UMB has antidiabetic and antihyperlipidemic effects in diabetic rats.
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PMID:Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats. 1672 13

Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced insulin secretion. Antidiabetic therapy based on GIP holds great promise because of the fact that its insulinotropic action is highly dependent on the level of glucose, overcoming the sideeffects of hypoglycemia associated with the current therapy of Type 2 diabetes. The truncated peptide, GIP(1-30)NH2, has the same activity as the full length native peptide. We have studied the structure of GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR). The structure of GIP(1-30)NH2 in DMSO-d6 and H2O has been studied using 2D NMR (total correlation spectroscopy (TOCSY), nuclear overhauser effect spectroscopy (NOESY), double quantum filtered-COSY (DQF-COSY), 13C-heteronuclear single quantum correlation (HSQC) experiments, and its conformation built by MD simulations with the NMR data as constraints. The peptide in DMSO-d6 exhibits an alpha-helix between residues Ile12 and Lys30 with a discontinuity at residues Gln19 and Gln20. In H2O, the alpha-helix starts at Ile7, breaks off at Gln19, and then continues right through to Lys30. GIP(1-30)NH2 has all the structural features of peptides belonging to family B1 GPCRs, which are characterized by a coil at the N-terminal and a long C-terminal alpha-helix with or without a break. A model of the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on the principles of comparative protein modeling, using the crystal structure of bovine rhodopsin as a template. The N-terminal domain of GIPR has been constructed from the NMR structure of the N-terminal of corticoptropin releasing factor receptor (CRFR), a family B1 GCPR. The intra and extra cellular loops and the C-terminal have been modeled from fragments retrieved from the PDB. On the basis of the experimental data available for some members of family B1 GPCRs, four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex. The model can rationalize the various experimental observations including the potency of the truncated GIP peptide. This work is the first complete model at the atomic level of GIP(1-30)NH2 and of the complex with its GPCR.
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PMID:Understanding interactions of gastric inhibitory polypeptide (GIP) with its G-protein coupled receptor through NMR and molecular modeling. 1743 46


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