Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gliclazide is the most commonly used sulfonylurea derivative for NIDDM therapy. Due to its prolonged therapy, there is always a likelihood of its use with other drugs. On the other hand antacids are commonly prescribed to encounter gastric acidity etc. Present paper deals with the in vitro availability studies of gliclazide in presence of antacids. These studies were carried out in simulated gastric juice and in buffer of pH 7.4 at body and accelerated temperature. The antacids used in these studies were aluminum hydroxide, aluminum trisilicate, magnesium oxide, magnesium trisilicate, sodium bicarbonate, calcium carbonate, magaldrate and simethicone (2,4-dimethoxypoly-siloxane). It has been found that in case of magnesium oxide, magnesium trisilicate and sodium bicarbonate, availability of gliclazide was enhanced while in rest of the antacids retarded the availability of gliclazide.
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PMID:In vitro availability of gliclazide in presence of antacids. 1641 65

The metabolic syndrome describes a cluster of metabolic features that increases the risk for type 2 diabetes mellitus and cardiovascular disease. The prevalence of uric acid nephrolithiasis is higher among stone-forming patients with features of the metabolic syndrome such as obesity and/or type 2 diabetes mellitus. The major determinant in the development of idiopathic uric acid stones is an abnormally low urinary pH. The unduly urinary acidity in uric acid stone formers increasingly is recognized to be one of the features observed in the metabolic syndrome. Two major abnormalities have been implicated to explain this overly acidic urine: (1) increased net acid excretion, and (2) impaired buffering caused by defective urinary ammonium excretion, with the combination resulting in abnormally acidic urine. New information is emerging linking these defects to changes in insulin signaling in the kidney. This article reviews the epidemiologic and metabolic studies linking uric acid nephrolithiasis with the metabolic syndrome, and examines the potential mechanisms underlying the unduly acidic urine in these conditions.
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PMID:Metabolic syndrome and uric acid nephrolithiasis. 1835 98

Catalytic drugs based on target-selective artificial proteases have been proposed as a new paradigm in drug design. Peptide-cleavage agents selective for pathogenic proteins of Alzheimer's disease, type 2 diabetes mellitus or Parkinson's disease have been prepared using the Co(III) aqua complex (Co(III)cyclen) of 1,4,7,10-tetraazacyclododecane as the catalytic center. In the present study, the Co(III) aqua complex (Co(III)oxacyclen) of 1-oxa-4,7,10-triazacyclododecane was examined in search of an improved catalytic center for peptide-cleavage agents. An X-ray crystallographic study of [Co(oxacyclen)(CO(3))](ClO(4)), titration of Co(III)oxacyclen, and kinetic studies on the cleavage of albumin, gamma-globulin, lysozyme, and myoglobin by Co(III)oxacyclen were carried out. Considerably higher proteolytic activity was observed for Co(III)oxacyclen in comparison with Co(III)cyclen, indicating that better target-selective artificial metalloproteases would be obtained using Co(III)oxacyclen as the catalytic center. The improved proteolytic activity was attributed to either steric effects or the increased Lewis acidity of the Co(III) center. The kinetic data also predicted that side effects due to the cleavage of nontarget proteins by a catalytic drug based on Co(III)oxacyclen would be insignificant.
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PMID:Proteolytic activity of Co(III) complex of 1-oxa-4,7,10-triazacyclododecane: a new catalytic center for peptide-cleavage agents. 1883 52

The incidence of both type 1 and type 2 diabetes is increasing and although environmental pollutants are believed to be potential culprits, the extent to which they can be held responsible remains uncertain. Some bacterial strains of the Bacillus cereus produce a toxin, cereulide, which is frequently found in starchy meals and which is difficult to eradicate from the food chain as it is highly resistant to heat, acidity and proteolysis. While cereulide is well known to cause acute emetic toxicity when ingested at high doses, several in vitro studies have shown that also extremely low doses of cereulide can be toxic, with beta cells being particularly sensitive. Mechanistically, such low doses impair the mitochondrial activity of the beta cells thereby leading to hampered insulin secretion and cell death, both key traits in the pathophysiology of diabetes. In vivo studies of chronic or repeated low dose exposure to cereulide are currently lacking, but should be performed to further clarify the true relevance of cereulide as a potential environmental contributor to the ongoing diabetes epidemic.
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PMID:Cereulide food toxin, beta cell function and diabetes: Facts and hypotheses. 2599 18

The article analyzes Russian and international literature examining specific features of the pathogenesis of renal stones in the setting of carbohydrate metabolism disorders. The authors outline the renal effects of the main pharmacological groups of oral hypoglycemic drugs regarding metaphylaxis of nephrolithiasis. An increased risk of nephrolithiasis in type 2 diabetes mellitus is realized through hyperuricemia with concurrent urine acidification. Current literature is lacking studies on the effects of oral hypoglycemic drugs on urine properties. There are reports about the tendency of biguanides (metformin) to shift the urine reaction to the acid side. Derivatives of sulfonylureas, incretins and inhibitors of dipeptidyl peptidase-4, do not significantly affect the urinary acidity and urinary salt excretion. Inhibitors of sodium-glucose cotransporter type 2 (gliflozins) tend to reduce the blood level of urate, but the mechanism of this effect and the safety of these drugs in the setting of urolithiasis have not yet been investigated.
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PMID:[Nephrolithiasis coexisting with type 2 diabetes: current concept of the features of stone formation and the effects of hypoglycemic therapy on lithogenesis]. 2884 46

Multiple myeloma (MM) is a hematological malignancy with a poor prognosis while with a long and progressive outcome. To date, the therapeutic options are restricted to few drugs, including thalidomide or its derivates and autologous transplantation including stem-cell transplantation. More recently, the use of both proteasome inhibitors and monoclonal antibodies have been included in MM therapy, but the clinical results are still under evaluation. Unfortunately, death rates (within the 5-year overall survival rates) are still very high (45%), with no relevant improvement over the past 10 years. Here, we discuss data supporting a new therapeutic approach against MM, based on a common phenotype of tumor malignancies, which is the acidic microenvironment. Extracellular acidity drastically reduces the efficacy of both anti-tumor drugs and the immune reaction against tumors. Pre-clinical data have shown that anti-acidic drugs, such as proton pump inhibitors (PPIs), have a potent cytotoxic effect against human MM cells, thus supporting their use in the treatment of this malignancy. Here, we discuss also similarities between MM and type II diabetes mellitus (DM) with high risk of developing MM, suggesting that both anti-diabetic drugs and a hypocaloric diet may help in curing MM patients.
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PMID:The Acidic Microenvironment: Is It a Phenotype of All Cancers? A Focus on Multiple Myeloma and Some Analogies with Diabetes Mellitus. 3314 95