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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphorus is the sixth most abundant element in the body after oxygen, hydrogen, carbon, nitrogen, and calcium. It comprises about 1% of the total body weight of humans. Eighty-five percent of it is stored in the bone in the form of hydroxyapatite crystal; 14% is in the soft tissues in the form of energy-storing bonds with nucleotides (ATP, GTP), nucleic acids in chromosomes and ribosomes, 2,3-DPG in the red blood cells, and phospholipids in the cells' membranes. Less than 1% is in the extracellular fluids. Phosphate balance is maintained by multiple systems. The gut is responsible for the absorption of two thirds of the 4-30 mg/kg/day of phosphate intake. Absorption sites are all along the gut; in humans the most active site is the jejunum. The kidney filters 90% of the plasma phosphate and reabsorbs it in the tubuli. In states of hypophosphatemia the kidney can reabsorb the filtered phosphates very efficiently, reducing the amount excreted in the urine virtually to zero. The healthy kidney can excrete high loads of phosphate and rid the body of phosphate overload. Through the vitamin D-PTH axis the endocrine system regulates the phosphate balance by influencing the kidney, gut, and bone. Other hormones, including thyroid, insulin, glucagon, glucocorticosteroid, and thyrocalcitonin, play a lesser role in regulation of phosphate metabolism. Because of the complex control of phosphate homeostasis, various clinical conditions may lead to hypophosphatemia. These include nutritional repletion, gastrointestinal malabsorption, use of phosphate binders, starvation, diabetes mellitus, and increased urinary losses due to tubular dysfunction. The clinical picture of phosphate depletion is manifested in different organs and is due mainly to the fall in intracellular levels of ATP and decreased availability of oxygen to the tissues, secondary to 2,3-DPG depletion. The various manifestations of phosphate depletion are listed in Table 2. The treatment of hypophosphatemia consists of administering enteral or parenteral phosphate salts. An important aspect of dealing with the potentially serious effects of phosphate depletion is to prevent the depletion from happening in the first place. Hyperphosphatemia can occur in renal failure, hemolysis, tumor lysis syndrome, and rhabdomyolysis. The treatment of hyperphosphatemia usually consists of fluid administration (in the absence of kidney failure). In chronic hyperphosphatemia, phosphate binders such as aluminum and magnesium salts can reduce the phosphate load. The use of these phosphate binders is limited by their potential side effects.
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PMID:Consequences of phosphate imbalance. 306 Jan 61

Nuclear magnetic resonance (NMR) spectroscopy has been utilized in the study of the metabolism of intact, functioning rabbit lenses maintained in organ culture. The sorbitol pathway and aldose reductase inhibition have been studied using carbon-13 NMR spectroscopy. Incubation of lenses in high concentration [1-13C] glucose medium with and without added inhibitors allows the sorbitol pathway and glycolysis to be monitored. Various aldose reductase inhibitors have been studied and are ranked based on percentage of inhibition as follows: tolrestat greater than or equal to sorbinil greater than sulindac greater than sulindac sulfide much greater than indomethacin greater than acetylsalicylic acid greater than quercetin greater than tandearil greater than salicylic acid greater than 3,3-Tetramethyleneglutaric acid (TMG). It has been demonstrated that 13C NMR spectroscopy provides an effective method of screening potential inhibitors of aldose reductase. The aspirin substitutes ibuprofen and acetaminophen have been studied and are found to reduce sorbitol accumulation in intact rabbit lenses. The effects of myo-inositol and vitamin E on sorbitol accumulation have also been investigated. Results suggest that the various metabolic pathways within the lens are intricately connected. In a preliminary manner, the effect of diabetes on metabolism in intact lenses has been investigated using 13C NMR spectroscopy. Increased sorbitol production has been observed for diabetic lenses. 31P NMR spectroscopy has also been utilized in the study of lens metabolism and aldose reductase inhibitors. Inclusion of various inhibitors in the high concentration glucose medium results in maintenance of essentially normal phosphorus-containing metabolite levels in the lens. No clear relationship was observed between lens clarity and phosphorus metabolite levels as determined using NMR.
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PMID:The utilization of 13C and 31P nuclear magnetic resonance spectroscopy in the study of the sorbitol pathway and aldose reductase inhibition in intact rabbit lenses. 311 3

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopic analyses of the crystalline lens from the experimental diabetic rat were performed. Qualitative and quantitative alterations in the phosphorus-31 NMR metabolic profile were observed over the course of 3 weeks after the induction of diabetes mellitus. Most striking was the appearance of two new, as yet unidentified, metabolites. These metabolites which resonate at 6.6 and 5.8 ppm were not detected in the normal lens. Compared to the normal lens, glycerol-3-phosphate (G3P) underwent an eightfold increase in concentration and phosphorylcholine decreased to one-third its initial level. The phosphodiesters, glycerophosphorylcholine (GPC) and glycerophosphorylethanolamine (GPE), decreased to barely detectable levels. Oral treatment of the diabetic animal with an aldose reductase inhibitor resulted in the preservation of an essentially normal lens 31P NMR spectrum. Except for the changes observed in glycerol-3-phosphate, these alterations have not been previously reported and raise new questions about the metabolic consequences of diabetes mellitus and the dependence of these alterations on the action of a single enzyme, aldose reductase.
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PMID:31P NMR studies of the diabetic lens. 313 82

The present studies were undertaken in an effort to determine whether somatomedins (SMs) play a role in the elevation of serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] levels during dietary phosphate deprivation. Serum 1,25-(OH)2D3,SM-C, and phosphate levels were measured in rats fed diets containing adequate or very low levels of dietary phosphorus under circumstances known to affect SM levels, including hypophysectomy with and without GH replacement, normal protein vs. low protein diets, and streptozotocin-induced diabetes with and without insulin replacement. In all circumstances, serum 1,25-(OH)2D3 concentrations were directly related to serum SM-C levels. However, the slope for the relationship was increased 2- to 10-fold in animals fed the low phosphorus diets. As observed previously, serum 1,25-(OH)2D3 levels were inversely related to serum phosphate levels, but the slope for this relationship was deceased in the presence of low SM levels and absent in animals with very low SM levels. These results suggest that SM are required for elevation of serum 1,25-(OH)2D3 levels in response to phosphate deprivation.
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PMID:Evidence that somatomedins mediate the effect of hypophosphatemia to increase serum 1,25-dihydroxyvitamin D3 levels in rats. 329 47

A previous study has shown that oral glucose administration results in a transient fall in urinary acid excretion in humans. The present study was undertaken to determine the effect of physiologic doses of insulin on urinary acidification while maintaining serum glucose concentration constant. This was accomplished by using a euglycemic insulin clamp method. Eight patients with insulin-dependent diabetes and no clinical or laboratory evidence of detectable renal disease were studied. Data obtained during two 2-hour periods of steady state insulin infusion rates of 0.2 and 0.5 mU/kg/min were compared. This resulted in steady state serum free insulin levels of 15 +/- 0.1 and 39 +/- 0.6 uU/ml respectively. Urinary pH and bicarbonate excretion rate rose while the excretion rates of titratable acid, ammonium and net acid fell significantly with increased insulin administration. These changes occurred in the absence of any significant changes in serum glucose, potassium, Ca2+ or phosphorus concentrations or urinary excretion rates of Na+, K+, phosphorus or Ca2+. These data suggest that increased insulin levels within the physiological range can result in a transient fall in the rate of urinary acid excretion. These findings confirm previous observations in animals and suggest that insulin may be the cause of post prandial urinary "alkaline tide".
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PMID:Effect of human insulin administration on urinary acidification in patients with insulin-dependent diabetes. 330 24

Bone mineral content (BMC), mineral homeostasis, and diabetes control were evaluated in 31 Caucasian insulin-dependent diabetic patients (disease duration 18.3 +/- 7.7 yr, mean +/- SD) with normal kidney function. To evaluate bone mass, we performed radiogrammetry and single- and dual-photon absorptiometry. In women, a significantly lower mean BMC was found in the distal radius, at a mixed trabecular-cortical (P less than .01) and a cortical (P less than .05) site, as well as in the lumbar spine (P less than .02). In diabetic men, mean BMC was significantly reduced at the trabecularcortical (P less than .01) and cortical (P less than .05) sites of the radius but not in the lumbar spine. When expressed as densities (i.e., BMC/width or lumbar BMC/area), only the BMC/width at the radius cortical area was significantly reduced in women (P less than .05). The results of the radiogrammetry showed a larger endosteal diameter in the diabetic women, resulting in a significantly lower cortical thickness (P less than .05). Diabetic men did not show abnormalities on radiogrammetry. Diabetic patients had diminished serum calcium and phosphorus concentrations (P less than .001), whereas serum parathyroid, 25-hydroxyvitamin D3, and concentrations of both total and free 1,25-dihydroxyvitamin D3 were normal. No correlation between parameters of diabetes control (HbA1, insulin dose, and triglycerides) or calcium-regulating hormones and BMC were found. These data confirm that, despite large overlap of individual values, mean bone mass at the peripheral skeleton is significantly decreased in diabetic patients. Moreover, we report that the BMC of the lumbar spine is significantly reduced in female diabetic patients.
Diabetes 1988 Jan
PMID:Mineral metabolism and bone mass at peripheral and axial skeleton in diabetes mellitus. 333 79

The effect of diabetes on maternal bone mineral metabolism and fetal mineralization was studied in nonpregnant and pregnant BB rats fed two diets (0.85% calcium-0.7% phosphorus and 0.2% calcium-phosphorus). Non-pregnant female diabetic rats had normal total bone mineral content (BMC), despite decreased trabecular bone volume density (TBVD). Nondiabetic rats on the low calcium-phosphorus diet showed decreased TBVD, signs of increased bone turnover, and decreased BMC; plasma 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3] was increased and urinary calcium excretion was decreased. A similar response was observed in diabetic rats with a further decrease in TBVD. Nondiabetic 21-day pregnant rats on high and low calcium-phosphorus diets had higher 1,25(OH)2D3 than nonpregnant rats (98 vs. 58 and 328 vs. 147 pg/ml, respectively). Maternal BMC did not change during pregnancy but was decreased by the low calcium-phosphorus diet; fetal mineral content was not influenced by the low calcium-phosphorus regime. No increase in 1,25(OH)2D3 was observed in pregnant diabetic rats (57 vs. 52 and 112 vs. 128 pg/ml in high and low calcium-phosphorus diet groups). Fetal mineralization was severely impaired in diabetes but was not further decreased by the low calcium-phosphorus diet. Thus nonpregnant diabetic rats respond normally to a low calcium-phosphorus diet, but pregnant diabetic rats do not show increased 1,25(OH)2D3 levels due to impairment of fetal mineralization.
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PMID:Diabetes and low Ca-P diet have opposite effects on adult and fetal bone mineral metabolism. 335 64

The autonomy and functional role of fetal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH)2D3 were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH)2D3 levels were correlated (r = 0.80; P less than 0.001). The vitamin D-dependent calcium-binding proteins (CaBP9K and CaBP28K) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP9K and CaBP28K in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH)2D3 levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP9K and renal CaBPs, but placental CaBP9K was not different. In diabetic pregnant rats, duodenal CaBP9K tended to be lower, while renal CaBPs were normal; placental CaBP9K was decreased. No significant changes in CaBP levels were observed in fetuses of low calcium-phosphorus diet rats or fetuses of diabetic rats. The results indicate that in the rat fetal 1,25(OH)2D3 depends on maternal 1,25(OH)2D3 or on factors regulating maternal 1,25(OH)2D3. The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH)2D3 levels confirms earlier data showing that 1,25(OH)2D3 has a limited hormonal function during perinatal development in the rat.
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PMID:1,25(OH)2D3 and Ca-binding protein in fetal rats: relationship to the maternal vitamin D status. 335 65

The substrate specificities of calcium/phospholipid-dependent kinase-C (PKC) were examined in rat kidney cortex, and localization of the protein was studied after the induction of diabetes. The cytosolic kinase was eluted from an anion exchange resin using a linear gradient of 0-0.15 M NaCl. A sharp peak of activity was demonstrated at approximately 80 mM using histone as a substrate. The kinase demonstrated a broad pH optimum of 6.5-8.0. ATP was the preferred phosphorus donor. The Ka for ATP averaged 2.6 +/- 0.1 microM (n = 4) and was not different in diabetic animals. Lysine-rich histones, but not arginine-rich or mixed histones, were the most suitable phosphorus acceptors. Phosphatidylserine stimulated kinase activity with Ka of 4.5 +/- 0.7 microM in the presence of 20 microM diolein (n = 3). Twenty micromolar diolein in the presence of 25 microM phosphatidylserine lowered the apparent Ka for calcium from 17.2 +/- 1.4 to 3.3 +/- 1.5 microM (n = 3; P less than 0.01). Similar data were evident in diabetic animals. Diabetic renal growth was induced by the injection of streptozotocin (35 mg/kg, iv). At the end of 4 weeks, blood glucose averaged 119.6 +/- 7.4 mg/dl in vehicle-injected controls and 548.7 +/- 21.6 mg/dl in diabetic animals (n = 5; P less than 0.001). Despite reduced weight gains in diabetic animals, renal protein content was increased in this group compared to the control value. Neither cytosolic nor proximal tubule basolateral membrane PKC activity changed after the induction of diabetes; however, luminal brush border PKC activity increased from 83.8 +/- 4.6 pmol/mg.min in control animals to 107.3 +/- 55 pmol/mg.min in diabetic animals (n = 5; P less than 0.02). The increased activity in the brush border membrane may have important consequences for the growth response of the kidney in diabetes.
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PMID:Characterization and localization of calcium/phospholipid-dependent protein kinase-C during diabetic renal growth. 340 97

Double photon absorptiometry comparison was done of lumbar bone mineral content (BMC) values in 40 women with well-compensated non-insulin-dependent diabetes mellitus (type II) and on dietary and/or oral hypoglycemic treatment, and 35 age-matched non-diabetic women, to determine the presence and degree of osteoporosis in this type of diabetes by means of a highly precise and sensitive method. No difference between the two groups was noted as regards blood calcium, phosphorus, PTH and thyrocalcitonin, and urinary calcium and phosphorus. BMC, on the other hand, was significantly lower in the diabetics, both in L2,L3,L4 and in L4 alone. No significant difference could be discerned between patients on diet and those on drugs. It can thus be maintained that osteoporosis is a possible complication of type II diabetes and may appear even in the absence of its classical complications.
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PMID:Osteoporosis in type II diabetes. 343 1


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