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

The effects of early-stage diabetes on disposition and renal handling of cefazolin (CEZ) were investigated in streptozotocin-induced diabetic rats. Significant increase in renal clearance was found in the diabetic rats (88%) and a strong correlation was obtained between renal and systemic clearance; however, there was no change in the volume of distribution. The results suggest that systemic clearance was increased as the result of enhancement of urinary excretion rate. Unbound fraction of CEZ in plasma was also increased by 60% in the diabetic rats and the increase may be due to the increase in glycosylated protein and plasma-free fatty acids. The filtration clearance for free drug in diabetic rats, which was estimated as glomerular filtration rate, was increased by about 1.9-fold compared to the normal rats, but the secretion clearance did not change in the two groups. Since kidney hypertrophy was observed in the diabetic rats, filtration and secretion clearance for free drug were normalized by means of kidney weight. After normalization for kidney weight, the two parameters were significantly reduced, indicating that the true kidney functions were impaired under the diabetic state. The parameters for CEZ secretion, maximum velocity and Michaelis-Menten constant, were also reduced in diabetic rats, suggesting that proximal tubule cell functions for secretion were altered in the diabetic rats. These results suggest that systemic and renal clearance was apparently increased in early-stage diabetes, whereas true kidney functions were impaired.
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PMID:Effect of diabetes on disposition and renal handling of cefazolin in rats. 198 3

Is increased synthesis of proteins responsible for the hypertrophy of kidney cells in diabetes mellitus? Does the lack of insulin, and/or the effect of insulin-like growth factor I (IGFI) on renal tubule protein synthesis play a role in diabetic renal hypertrophy? To answer these questions, we determined the rates of 3H-valine incorporation into tubule proteins and the valine-tRNA specific activity, in the presence or absence of insulin and/or IGFI, in proximal tubule suspension isolated from kidneys of streptozotocin diabetic and control rats. The rate of protein synthesis increased, while the stimulatory effects of insulin and IGFI on tubule protein synthesis were reduced, early (96 hours) after induction of experimental diabetes. Thus, hypertrophy of the kidneys in experimental diabetes mellitus is associated with increases in protein synthesis, rather than with decreases in protein degradation. Factor(s) other than the lack of insulin, or the effects of IGFI, must be responsible for the high rate of protein synthesis present in the hypertrophying tubules of diabetic rats.
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PMID:Renal protein synthesis in diabetes mellitus: effects of insulin and insulin-like growth factor I. 204 44

Renal tubular acidosis refers to a group of disorders that result from pure tubular damage without concomitant glomerular damage. They could be hereditary (primary) or acquired (secondary to various disease states like sickle cell disease, obstructive uropathy, postrenal transplant, autoimmune disease, or drugs). The hallmark of the disorder is the presence of hyperchloremic metabolic acidosis with, or without, associated defects in potassium homeostasis, a UpH greater than 5.5 in the presence of systemic acidemia, and absence of an easily identifiable cause of the acidemia. There are three physiologic types whose basic defects are impairment of or a decrease in acid excretion, i.e., type 1 (dRTA); a failure in bicarbonate reabsorption, i.e., type 2 (pRTA); and deficiency of buffer or impaired generation of NH4+, i.e., type 4 RTA. Several pathophysiologic mechanisms have been postulated for these various types. pRTA is the least common of all in the adult population. It rarely occurs as an isolated defect. It is frequently accompanied by diffuse proximal tubule transport defects with aminoaciduria, glycosuria, hyperphosphaturia, and so forth (Fanconi syndrome). dRTA is associated with a high incidence of nephrolithiasis, nephrocalcinosis, osteodystrophy, and growth retardation (in children). Osteodystrophy also occurs in pRTA to a lesser degree and is believed to be secondary to hypophosphatemia. Patients with type 4 RTA usually have mild renal insufficiency from either diabetes mellitus or interstitial nephritis. Acute bicarbonate loading will result in a high fractional excretion of bicarbonate greater than 15% (FEHCO3- greater than 15%) in patients with pRTA, but FEHCO3- less than 3% in patients with dRTA. Type I patients will also have a low (U - B) PCO2 with bicarbonate loading. They are also unable to lower their urine pH to less than 5.5 with NH4Cl loading. The treatment of these patients involves avoidance of precipitating factors when possible, treatment of underlying disease, correction of electrolyte imbalance, particularly hypokalemia and hyperkalemia, and most importantly, the use of alkali. This will prevent or reduce all the various complications.
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PMID:Renal tubular acidosis. 208 16

The human proximal tubule (HPT) is the characteristic site within the kidney that mediates absorption of glucose. This study was designed to determine whether cultured HPT cells would respond to a hyperglycemic environment through activation of the polyol pathway. The results of this study clearly indicate that exposure of the HPT cells to an extracellular glucose concentration greater than or equal to 11 mM results in substantial intracellular accumulation of sorbitol. This accumulation is inhibited by approximately 70% by treatment with 100 microM sorbinil. When cells growing 24 h on 27.5 mM glucose were changed to medium containing 5.5 mM glucose, sorbitol concentration returned to the control level within 12 h. The activity of aldose reductase was increased by a factor of 1.6 by exposure to elevated glucose concentrations, and the relative reactivity of the enzyme with glucose as substrate was approximately 0.1 compared with that of glyceraldehyde as substrate. Together, these results indicate that cultured cells derived from the HPT undergo activation of the polyol pathway when exposed to a hyperglycemic environment.
Diabetes 1990 Aug
PMID:Elicitation of sorbitol accumulation in cultured human proximal tubule cells by elevated glucose concentrations. 211 81

Because insulin shows an antinatriuretic effect in healthy humans, insulin therapy resulting in circulating hyperinsulinemia may lead to sodium retention and in turn to hypertension in individuals with insulin-dependent diabetes mellitus (IDDM). Moreover, it has been proved that atrial natriuretic peptide (ANP) plays a major role in modulating natriuresis in humans. This study investigated the relationship between insulin and ANP in modulating sodium metabolism in normotensive and hypertensive IDDM subjects compared with control groups of normotensive and hypertensive nondiabetic subjects. IDDM normotensive and hypertensive subjects had mean +/- SE duration of IDDM of 7 +/- 2 and 8 +/- 2 yr, respectively, and had no clinical features of diabetic nephropathy. All subjects received a saline infusion (2 mmol.kg-1.90 min-1) during euglycemia. IDDM normotensive and hypertensive subjects received a subcutaneous insulin infusion (15 mU.kg-1.h-1), resulting in twofold higher plasma free-insulin levels (16 +/- 2 and 19 +/- 3 microU/ml, respectively) than in nondiabetic normotensive and hypertensive subjects (7 +/- 2 and 8 +/- 2 microU/ml, respectively). During saline challenge, sodium excretion increased by 22 +/- 4% in normotensive and 49 +/- 9% in hypertensive nondiabetic subjects but by only 11 +/- 0.4% in normotensive (P less than 0.01) and 8 +/- 2% in hypertensive (P less than 0.01) IDDM subjects. The impaired natriuretic response to saline challenge was mainly due to greater rates of sodium reabsorption by kidney proximal tubules in IDDM than nondiabetic subjects. At baseline, plasma ANP concentrations were significantly higher in both IDDM groups than in control groups (normotensive IDDM and control subjects: 38 +/- 4 and 19 +/- 2 pg/ml, respectively, P less than 0.01; hypertensive IDDM and control subjects: 45 +/- 6 and 27 +/- 4 pg/ml, respectively, P less than 0.05). After saline challenge, ANP concentrations rose to 39 +/- 4 pg/ml in normotensive and 49 +/- 5 pg/ml in hypertensive control subjects, whereas no significant change above baseline value was seen in IDDM subjects. Both IDDM groups showed a 10-12% greater exchangeable Na+ pool than control subjects regardless of the presence of hypertension. Subcutaneous insulin infusion, resulting in circulating plasma free-insulin levels in normotensive control subjects comparable to those in IDDM patients, inhibited natriuresis, increased proximal tubule sodium reabsorption at the level of the kidney, and inhibited an adequate ANP stimulation by saline challenge. We conclude that hyperinsulinemia leads to increased proximal tubule sodium reabsorption and impaired ANP response during saline administration. Both mechanisms account for sodium retention in normotensive and hypertensive IDDM patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1990 Mar
PMID:Role of insulin and atrial natriuretic peptide in sodium retention in insulin-treated IDDM patients during isotonic volume expansion. 213 1

The protein A-gold immunocytochemical technique was applied to reveal the monomeric elements M1, M2* and M3 from the non-collagenous globular domain (NC1) of type IV collagen over various renal basement membranes from control and long-term streptozotocin-induced diabetic rats. This study includes the basement membranes of the proximal tubule, the Bowman's capsule and the glomerulus as well as the extracellular matrix of the mesangium. The labellings obtained were confined to basement membrane material. The quantitative analysis demonstrated changes in labelling intensities and distribution between tissues from normal and diabetic animals. Increased labelling intensities were observed for M1 and M2* monomers in all the basement membranes studied except for the mesangial matrix which remained unchanged. In addition, the labelling for M1 monomers, present on the endothelial side of the glomerular basement membrane of control animals, was found to be distributed throughout the entire thickness of the basement membrane of diabetic animals. In contrast, neither the intensity of the labelling, nor the distribution of M3 monomers were altered in diabetic animals. Since M1 monomers are markers of the alpha 1(IV) and alpha 2(IV) chains of type IV collagen while M2* and M3 mark alpha 3(IV) and alpha 4(IV) chains respectively, the present results demonstrate changes in the nature of the collagenous elements of basement membranes during diabetes. Furthermore, the results indicate that the alpha 3(IV) and the alpha 4(IV) chains are not necessarily present in the same molecule. The modifications of the collagenous elements of the basement membranes during diabetes must alter the structural characteristics of these matrices which in turn might influence their functional properties.
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PMID:Immunogold studies of monomeric elements from the globular domain (NC1) of type IV collagen in renal basement membranes during experimental diabetes in the rat. 215 Jan 95

In an earlier study, we described the presence of a retroendocytotic pathway for insulin in a cultured kidney epithelial cell line. Derived from the opossum kidney (OK), these cells possess many features of proximal tubule epithelium, which is the major site of kidney insulin metabolism. We studied the interaction between the retroendocytotic and the degradative pathways with bacitracin as a pharmacological probe. Monolayers of OK cells were loaded with 125I-labeled insulin over 30 min, acid washed to remove membrane-bound insulin, then incubated in fresh medium for 60 min while the release of intracellular radioactivity was monitored. In experiments carried out in the presence of bacitracin (2 mM), there was a two-thirds increase in intracellular radioactivity at the end of the loading phase. Measurements made during the subsequent release phase showed that bacitracin reduced the release of degradation products. Thus, although controls released 72.1 +/- 8.1% of the internalized radioactivity as trichloroacetic acid (TCA)-soluble products, bacitracin-treated cells released 59.2 +/- 9.4% (P less than 0.02). In contrast, release of TCA-precipitable insulin increased from 15.2 +/- 4.6% in controls to 25.8 +/- 3.7% in bacitracin-treated cells (P less than 0.01). In separate experiments analyzed by gel-exclusion chromatography, 6.4 +/- 0.6% of radioactivity released from preloaded control cells into medium over 60 min was insulin sized compared to 29.7 +/- 1.4% in bacitracin-treated cells. High-performance liquid chromatography revealed that 61.5 +/- 3.5% of this insulin-sized material released from control cells preloaded with A14-insulin eluted as intact insulin and the remainder as unidentified intermediate degradation products.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Nov
PMID:Effect of bacitracin on retroendocytosis and degradation of insulin in cultured kidney epithelial cell line. 222 8

In 68 type I diabetics without permanent proteinuria, mean age 28 +/- 9 years, where diabetes was detected at the age of 14 +/- 7 years and persists for 14 +/- 8 years the urinary excretion of albumin and beta-2-microglobulin was assessed. The results were evaluated in relation to the persistence of diabetes, the blood pressure reading, family-history of diabetes and type of insulin therapy. In addition to microalbuminuria in 29% of the subjects which is a manifestation of glomerular damage, the authors detected in 58% elevated beta-2-microglobulin excretion indicating early changes of the proximal tubule. There was a relationship between microalbuminuria and "relative hypertension" which enhances albumin excretion and increases the risk of diabetic nephropathy. The relationship between microalbuminuria and a positive family-history of diabetes supports the hypothesis of a genetic background for the possible development of nephropathy. There was also a relationship with the duration of diabetes and the favourable effect of prolonged intensive insulin treatment. The clinical impact of beta-2-microglobulinuria in the diagnosis of the incipient stage of diabetic nephropathy must be tested in future investigations.
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PMID:[Early diagnosis of nephropathy in type I diabetics]. 224 68

A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal beta-N-acetyl-glucosaminidase (beta-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, gamma-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein 'SGP-240' and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cis-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both 'soluble' and high-molecular-weight membrane particles (vacuolar blebs, greater than 10(6) dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular 'histuria' which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a very early phase.
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PMID:Urinary proteins of tubular origin: basic immunochemical and clinical aspects. 225 76

The effect of progressive increases in intraluminal glucose concentration on proximal tubule sodium absorption was studied in normal and streptozotocin diabetic rats by microperfusion. Each tubule was perfused twice, with and without glucose added to the perfusion fluid. Net sodium and water absorption were markedly enhanced by 300-500 mg% intraluminal glucose in both normal and diabetic rats. Substituting the transported but nonmetabolized glucose analogue, alpha-methyl D-glucoside for glucose also resulted in marked stimulation of sodium absorption, whereas substituting bicarbonate and acetate for chloride in the perfusion solution inhibited the effect of glucose. These observations suggest that the stimulation of sodium absorption by glucose was mediated by the brush border Na/glucose cotransporter. Sodium concentration and osmolality were found to fall markedly to hypotonic levels when high glucose concentrations were in the perfusion fluid. This luminal hypotonicity may be an important driving force for proximal fluid absorption. In poorly controlled diabetes, high filtered glucose concentrations may lead to enhanced proximal sodium and water absorption, which could in turn contribute to volume expansion, hypertension, and renal hypertrophy.
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PMID:Progressive increases in luminal glucose stimulate proximal sodium absorption in normal and diabetic rats. 236 20


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