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)

Calcium re-absorption in the kidney is impaired in streptozotocin (STZ) diabetic rats, thereby causing hypercalciuria. Increased calcium loss starts within 1-2 days after induction of diabetes and reaches a plateau after 2 weeks. The excessive calcium excretion was previously shown to be reduced by treatment with gamma-linolenic acid (GLA) or evening primrose oil rich in GLA. However, in these studies, the animals were pre-treated for several weeks before injection of STZ. In the present study we investigated whether GLA can reduce calcium excretion when treatment starts at the same time as induction of diabetes. Rats were made diabetic with 60 mg/kg STZ and at the same time food was fortified with 0.4% GLA for the treatment group. A control group was treated with vehicle alone and given standard feed only. Urine was collected from animals in metabolism cages every 3rd day for a period of 26 days. The diabetic group increased their food and water consumption, and urine and faeces production as compared to the control group. The urinary loss of Ca, Mg, Zn, Na, K and creatinine was markedly increased in the diabetic group as compared to the control. GLA treatment, however, did not affect any of these variables. Analysis of fatty acids in kidneys of the rats showed an increased concentration of GLA in the treated group as compared to the two non-treated groups. We conclude that GLA treatment must commence before STZ injection in order to attenuate diabetes-induced hypercalciuria.
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PMID:Failure of short-term gamma-linolenic acid treatment to reduce urinary calcium loss of diabetic rats. 1085 Jun 37

Altered divalent cation homeostasis with bone mineral loss, hypercalciuria, and hypomagnesemia have been associated consistently with human diabetes mellitus. This study investigated functional, molecular, and biochemical determinants that accompany this condition in chronically (2 wk) streptozotocin (STZ)-diabetic rats. Catheterized, conscious, diabetic rats on servo-controlled fluid replacement exhibited an increased GFR (+70%) and a substantially raised urinary calcium output (+568%) when compared with control rats. In addition, fractional calcium reabsorption was reduced, indicating that the hypercalciuria was not due solely to an osmotic effect but may involve an actual tubular defect. The expression of proteins involved in renal distal Ca2+ and water transport in STZ-diabetic rats were then studied by Western analysis and immunofluorescence microscopy to investigate the molecular basis of the hypercalciuria. Extracellular Ca2+-sensing receptor abundance was reduced to 52% of control in STZ-diabetes, whereas thiazide-sensitive NaCl cotransporter expression was increased by 192%. Subcutaneous insulin implant rectified both functional and molecular parameters. The levels of calbindin D(28k), plasma membrane Ca2+ ATPase, and aquaporin 1 in whole kidney and of aquaporin 2 in inner medulla were unchanged in diabetic and/or insulin replacement. Blood levels of 1,25(OH)(2)D(3) were reduced in diabetes as were levels of osteocalcin, a marker of bone formation. It is concluded that diabetic hypercalciuria in rats involves elevated GFR with raised urinary output, reduced Ca2+ reabsorption, and impaired bone deposition. Changes in Ca2+-sensing receptor and NaCl cotransporter protein expression could account for the altered divalent cation homeostasis seen during diabetes mellitus.
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PMID:Functional, molecular, and biochemical characterization of streptozotocin-induced diabetes. 1127 39

The pathogenesis of nephrolithiasis in Cushing's syndrome is still not completely clarified. The current study aimed at investigating prevalence of nephrolithiasis and role of different lithogenic factors in Cushing's disease (CD). Forty-six CD patients (24 with active and 22 with cured disease) and 46 sex- and age-matched controls entered the study. Body mass index, blood pressure, fasting glucose and insulin, serum and urinary creatinine, urea, uric acid, electrolytes, and cystine, urinary volume, pH, oxalate, and citrate levels, and renal ultrasonography (US) were performed in all patients and controls. Nephrolithiasis was found in 50% of active patients, 27.3% of cured patients, and 6.5% of controls (P < 0.001). Compared with controls, patients with active disease had a significantly increased prevalence of obesity, arterial hypertension, diabetes mellitus, hypercalciuria, hypocitraturia, and hyperuricosuria, significantly higher levels of serum and urinary cystine, urinary creatinine, urea, uric acid, potassium, calcium, phosphorus, and oxalate, significantly lower levels of urinary citrate levels. Compared with controls, patients cured from CD had a significantly increased prevalence of obesity, systemic arterial hypertension, and diabetes mellitus, whereas urinary citrate was significantly decreased. At multivariate analysis, a significantly increased risk to develop kidney stones was independently associated with urinary excretion of uric acid (odds ratio = 1.6, confidence interval = 1.0-2.5) and systemic arterial blood pressure (odds ratio = 2.6, confidence interval = 1.1-6.6). In conclusion, patients with active CD have an increased prevalence of nephrolithiasis compared with general population, which decreases but not disappears in patients successfully cured from the disease. This complication is likely caused by the synergic effect of different hypercortisolism-dependent metabolic and hemodynamic abnormalities, among which systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role.
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PMID:Nephrolithiasis in Cushing's disease: prevalence, etiopathogenesis, and modification after disease cure. 1272 57

Both diabetes and fractures affect a large proportion of older adults. Recent cohort studies indicate that diabetes itself is associated with increased risk of fracture of the hip, proximal humerus, and foot. Observational studies and animal models suggest that decreased bone strength in diabetes may contribute to fracture risk but this remains a controversial issue. Type 1 diabetes is associated with modest reductions in bone mineral density (BMD) but type 2 diabetes is often characterized by elevated BMD. This paradox of higher BMD but increased fracture risk in type 2 diabetes may be explained by a combination of more frequent falls and poorer bone quality. Diabetes can impact bone through multiple pathways, some with contradictory effects, including obesity, changes in insulin levels, higher concentrations of advanced glycation end products in collagen, hypercalciuria associated with glycosuria, reduced renal function, lower insulin-like growth factor-I, microangiopathy, and inflammation. A better understanding of how diabetes metabolism and treatments affect bone would improve fracture prevention efforts in older diabetic adults.
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PMID:Diabetes Mellitus: Does it Affect Bone? 1451 15

Diabetes mellitus and osteoporosis are chronic diseases with an elevated and growing incidence in the elderly. Recent epidemiological studies have demonstrated an elevated risk of hip, humerus and foot fractures in elder diabetic subjects. While type 1 diabetes is generally associated with a mild reduction in bone mineral density (BMD), type 2 diabetes, more prevalent in old subjects, is frequently linked to a normal or high BMD. Studies on experimental models of diabetes have suggested an altered bone structure that may help to explain the elevated risk of fractures observed in these animals and may as well help to explain the paradox of an incremented risk of fractures in type 2 diabetic elderly in the presence of normal or elevated BMD. In addition, diabetic elderly have an increased risk of falls, consequent at least in part to a poor vision, peripheral neuropathy, and weaken muscular performance. Diabetes may affect bone tissue by different mechanisms including obesity, hyperinsulinemia, deposit of advanced glycosilation end products in collagen fibre, reduced circulating levels of IGF-1, hypercalciuria, renal function impairment, microangiopathy and chronic inflammation. A better understanding of these mechanisms may help implement the prevention of fractures in the growing population of mature diabetics.
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PMID:[Osteoporosis and diabetes]. 1564 75

The polyol isomalt (Palatinit) is a well established sugar replacer. The impact of regular isomalt consumption on metabolism and parameters of gut function in nineteen healthy volunteers was examined in a randomised, double-blind, cross-over trial with two 4-week test periods. Volunteers received 30 g isomalt or 30 g sucrose daily as part of a controlled diet. In addition to clinical standard diagnostics, biomarkers and parameters currently discussed as risk factors for CHD, diabetes or obesity were analysed. Urine and stool Ca and phosphate excretions were measured. In addition, mean transit time, defecation frequency, stool consistency and weight were determined. Consumption of test products was affirmed by the urinary excretion of mannitol. Blood lipids were comparable in both phases, especially in volunteers with hyperlipidaemia, apart from lower apo A-1 (P=0.03) for all subjects. Remnant-like particles, oxidised LDL, NEFA, fructosamine and leptin were comparable and not influenced by isomalt. Ca and phosphate homeostasis was not affected. Stool frequency was moderately increased in the isomalt phase (P=0.006) without changes in stool consistency and stool water. This suggests that isomalt is well tolerated and that consumption of isomalt does not impair metabolic function or induce hypercalciuria. In addition, the study data indicate that isomalt could be useful in improving bowel function.
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PMID:Effects of isomalt consumption on gastrointestinal and metabolic parameters in healthy volunteers. 1619 83

The kidney function can be assessed by a number of methods. The urinary excretion of enzymes, in particular N-acetyl-beta-D-glucosaminidase (NAG), is considered a relatively simple, cheap, fast and non-invasive method in the detection and follow-up of renal tubular function under various conditions. The determination of urinary NAG provides a very sensitive and reliable indicator of renal damage, such as injury or dysfunction due to diabetes mellitus, nephrotic syndrome, inflammation, vesicoureteral reflux, urinary tract infection, hypercalciuria, urolithiasis, nephrocalcinosis, perinatal asphyxia, hypoxia, hypertension, heavy metals poisoning, treatment with aminoglycosides, valproate, or other nephrotoxic drugs. This paper gives an overview of the current use of urinary NAG in the detection of renal injury.
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PMID:The diagnostic role of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in the detection of renal tubular impairment. 1625 16

Diabetes mellitus and osteoporosis affect a large proportion of older adults. In this context, diabetes may influence the bone in multiple pathways, some with contradictory effects. These mechanisms include changes in insulin and insulin-like growth factors levels, hypercalciuria associated with glycosuria, reduced renal function, obesity, higher concentrations of advanced glycation end products in collagen, angiopathies, neuropathies and inflammation. Although it is assumed that the decreased bone strength in diabetes may contribute to fracture risk, a very high number of available clinical and/or epidemiological studies as well as animal model studies brought about heterogeneous or even contradictory results on the skeletal involvement in patients with diabetes mellitus. In addition, bone mineral density (BMD) is a convenient predictor for fracture and the type 1 diabetes is associated with modest reductions in BMD. However, type 2 diabetes can be related to the elevated BMD. The immediate improvement in these discrepancies is to consider the complex pathophysiology of diabetes as well as influences of gender, age, treatment and duration of the disease. It is important also to improve further the choice of investigated biochemical markers and the standardization of the bone mass measurements. Along these lines, several recent cohort studies undeniably indicated that diabetes itself is associated with increased risk of osteoporosis.
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PMID:The impact of diabetes mellitus on skeletal health: an established phenomenon with inestablished causes? 1631 62

The frequency of hypercalciuria is increasing in western countries with an incidence of nephrolithiasis which can reach 13%. Hypercalciuria appears as an alteration of the calcium transport system (kidney, bowel, bone) which is regulated by calcitriol and parathormone. The aim of this review was to screen etiologies of hypercalciuria taking into account recent genetic advances (calcium epithelial channel and calcium sensing receptor). Hypercalciuria may be favored by nutritional causes (diet rich in calcium, sodium, carbohydrates, proteins, poor in phosphates and potassium). It may also be related to an increase in calcium absorption (vitamin D excess, primary hyperparathyroidism, sarcoidosis, lymphoma, estrogens, and certain genetic causes), an increase in osteoresorption (bone metastasis, myeloma, Paget, hyperthyroidism, immobilization, hypercortisolism and corticosteroid therapy), or a decrease of kidney tubular resorption (diuretics, Cacci and Ricci, acromegally, Bartter, familial dominant hypocalcemia, Fanconi, Dent, familial hypomagnesemia-hypercalciuria syndrome, type 1 distal tubular acidosis, pseudohypoaldosteronism, diabetes). If no cause is identified, persistence of hypercalciuria after instituting a correct diet is defined as idiopathic hypercalciuria. Treatment of the cause is essential in secondary hypercalciuria, in addition to diet (low sodium intake, normocalcic diet, hydration), associated with thiazide diuretics and biphosphonates if necessary.
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PMID:[Hypercalciuria]. 1635 16

Diabetes is associated with renal calcium and magnesium wasting, but the molecular mechanisms of these defects are unknown. We measured renal calcium and magnesium handling and investigated the effects of diabetes on calcium and magnesium transporters in the thick ascending limb and distal convoluted tubule in streptozotocin (STZ)-induced diabetic rats. Rats were killed 2 weeks after inducing diabetes, gene expression of calcium and magnesium transporters in the kidney was determined by real-time polymerase chain reaction, and the abundance of protein was assessed by immunoblotting. Our results showed that diabetic rats had significant increase in the fractional excretion for calcium and magnesium (both P < 0.01), but not for sodium. Reverse transcriptase-polymerase chain reaction revealed significant increases in messenger RNA abundance of transient potential receptor (TRP) V5 (223 +/- 10%), TRPV6 (177 +/- 9%), calbindin-D28k (231 +/- 8%), and TRPM6 (165 +/- 8%) in diabetic rats. Sodium chloride cotransporter was also increased (207 +/- 10%). No change was found in paracellin-1 (cortex: 108 +/- 8%; medulla: 110 +/- 10%). Immunofluorescent studies of renal sections showed significant increase in calbindin-D28k (238 +/- 10%) and TRPV5 (211 +/- 10%), but no changes in paracellin-1 in Western blotting (cortex: 110 +/- 7%; medulla: 99 +/- 7%). Insulin administration completely corrected the hyperglycemia-associated hypercalciuria and hypermagnesiuria, and reversed the increase of calcium and magnesium transporter abundance. In conclusion, our results demonstrated increased renal calcium and magnesium transporter abundance in STZ-induced diabetic rats, which may represent a compensatory adaptation for the increased load of calcium and magnesium to the distal tubule.
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PMID:Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. 1655 23


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