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)

Renal clearance studies were performed on rats both during the administration of streptozotocin and sequentially during the following 8 days as hyperglycemia progressed. Although GFR was depressed 30 min after the drug administration, GFR steadily rose during the following days to become 52% greater than control levels. Renal size did not change during this short period, and it is suggested that glomerular hemodynamic changes are responsible. A maximal tubular reabsorptive capacity for glucose (TmG) could not be satisfactorily demonstrated in normal rats, although glucose reabsorption was significantly depressed at high-filtered loads. At comparable filtered loads, glucose reabsorption in diabetic rats was almost complete in contrast to normal rats, and the increases in GFR and renal tubular sodium reabsorption are presumed to be the major factors. The administration of insulin to normal and diabetic rats was followed by a significant diuresis as well as an increase of 1% to 4% in the fraction of filtered sodium excreted although GFR was unaltered. This shows that even a 35% to 60% reduction in the filtered load of glucose can significantly depress renal sodium reabsorption. It is concluded that this is a good animal model in which to study the effects of diabetes on renal function as well as the in vivo interrelationships of sodium and glucose reabsorption.
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PMID:Acute effects of streptozotocin diabetes on rat renal function. 15 16

Proteinuria has been analysed in 334 maturity-onset diabetics and 80 matched controls. Proteinuria measured in the recumbent position exceeded 100 mug/min in 53% of the diabetic population. The percentage of excessive proteinuria increased with duration of the disease. Sex and age had no influence. Out of 55 first year diabetics, 49% had abnormal quantitative proteinuria; this is in contrast to 76 longterm diabetics (over 12 years) of whom 38% had proteinuria under 100 mug/min. Electrophoresis and immuno-electrophoresis showed a glomerular pattern in 40%, a tubular pattern in 15% and a mixed pattern in 8% of all the diabetics. 32% of the diabetics with quantitatively normal proteinuria were abnormal qualitatively, and this may be the first manifestation of diabetic nephropathy. Thirty-eight other patients had a normal electrophoretic pattern in spite of increased proteinuria. Proteinuria levels were significantly associated with hematuria, bacteriuria and reduced GFR, but not with leukocyturia, insulin dependence and hypertension. Upright position increased the proteinuria to a greater degree amongst the patients with normal proteinuria. We discuss the role of increased filtration pressure and glomerular permeability in modifying proteinuria in diabetes. Sensitive quantitative and qualitative proteinuria determinations are important tools both in early diagnosis of diabetic nephropathy in clinical practice and in epidemiological studies.
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PMID:[Proteinuria in mature diabetic patients. Quantitative and qualitative analysis]. 121 95

In latent hereditary diabetes mellitus increased protein excretion has been found in male diabetic mice compared to controls. This proteinuria is partly due to an increased excretion of higher molecular weight proteins, which could be identified as deriving from plasma. The suggested glomerular proteinuria has been verified by an increase in the renal excretion of high molecular weight PVP. No changes in GFR occurred in this early stage of diabetic glomerulopathy. No changes in morphology could be detected, suggesting some changes in the biochemical membrane structure that cause the findings of increased permeability of the diabetic basement membrane for plasma proteins.
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PMID:Functional and morphological study on the onset of proteinuria in experimental diabetes mellitus. 123 92

Animal models and humans with glomerular hyperfiltration and hyperperfusion secondary to diabetes or high protein diet show increased renal production of kallikrein and kinins. Acute aminoacid infusion or ingestion also raises GFR, RPF and urinary kinins. Treatment with aprotinin or a kinin receptor antagonist reverses or prevents hyperfiltration in these rat models.
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PMID:Renal hyperfiltration states: relationship to kallikrein and kinins. 128 77

The pathogenetic determinants of sodium retention in IDDM are not fully understood. The aim of this study was to elucidate the action of ANP in 11 IDDM patients with high GFR (greater than or equal to 135 ml.min-1 x 1.73 m-2), referred to here as HF patients; in 10 IDDM patients with normal GFR (greater than 90 and less than 135 ml.min-1 x 1.73 m-2), referred to here as NF patients; and 12 control subjects, here called C subjects, at baseline and during saline infusion administered on the basis of either body weight (2 mmol.kg-1 x 60 min-1; Saline 1) or of ECV (12 mM.ECVL-1 x 90 min-1; Saline 2) during euglycemic insulin-glucose clamp. C subjects and both HF and NF IDDM patients received a second Saline 1 infusion accompanied by ANP infusion (0.02 microgram.kg-1.min-1) at euglycemic levels. HF and NF patients were studied again after 3 mo of treatment with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor without sulfhydryl group. At baseline, both HF and NF IDDM patients had higher plasma ANP concentrations than C subjects (HF, 36 +/- 4, P less than 0.01 and NF, 34 +/- 3, P less than 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P less than 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had still lower urinary sodium excretion rates. The simultaneous administration of ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF and NF patients. However, urinary sodium excretion rate was significantly lower in HF and NF patients than in C subjects: HF, 267 +/- 64, P less than 0.01 and NF, 281 +/- 42, P less than 0.01 vs. C, 424 +/- 39 mumol.min-1 x 1.73 m-2. During simultaneous administration of ANP and Saline 1, GFR and FF increased in C subjects, but not in HF and NF patients. HF and NF patients had higher urinary vasodilatory prostanoid excretion rates than C subjects at baseline. Saline infusion did not change urinary excretion rate of prostanoids either in C subjects or IDDM patients (both NF and HF).(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1992 Aug
PMID:Role of atrial natriuretic peptide in the pathogenesis of sodium retention in IDDM with and without glomerular hyperfiltration. 138 91

A number of risk factors associated with the development of diabetic nephropathy has been described, such as elevated blood pressure, poor metabolic control, hyperlipidemia, and smoking. Abnormal albuminuria also is associated with progression of renal disease, but has until recently been considered principally a marker of disease activity rather than a risk factor. This article discusses the role of elevated blood pressure versus abnormal albuminuria in a genesis and prediction of renal disease in diabetes. Controversy exists regarding parental disposition to hypertension and early blood pressure elevation in the course of diabetes, but all studies agree that elevated blood pressure--in the presence of abnormal albuminuria--constitutes a risk factor. Because abnormal albuminuria is associated with progression disease, it may itself be a risk factor because increased macromolecular traffic over the glomerular membrane may produce glomerulopathy. Problems related to blood pressure measurement are important, and 24-h recordings of blood pressure may be recommended in some situations. Regarding renal structure, preliminary results suggest that structural lesions precede blood pressure elevation. The solid end point for evaluation of renal disease progression is the fall rate of GFR, with abnormal albuminuria as an intermediate end point, also in drug trials. Abnormal albuminuria may constitute a new indication for antihypertensive treatment, being, as it is, a clear indicator of organ damage, whereas elevated blood pressure with normal AER may not increase risk substantially.
Diabetes Care 1992 Sep
PMID:Blood pressure elevation versus abnormal albuminuria in the genesis and prediction of renal disease in diabetes. 139 16

Not all patients with diabetes develop clinically significant nephropathy and, for this reason, attention has begun to focus on the risk factors for development of this serious complication. These risk factors have not been quantified to the same degree as those factors associated with more common progressive vascular diseases, such as atherosclerosis. However, studies of pathogenesis and clinical and epidemiological surveys of diabetic nephropathy point to numerous risk categories. Glycemic control, genetic and familial predispositions, renal and glomerular enlargement, glomerular hyperfiltration, and capillary and systemic hypertension can be invoked as contributors to this disease process. This review focuses on hemodynamic alterations and their role in the development and progression of diabetic nephropathy. Increases in GFR, largely driven by increases in plasma flow and capillary pressure, appear in early IDDM and NIDDM. This abnormality of renal vascular control probably is derived from alterations in several vasoactive control systems. In addition, the elevations in capillary pressure may be damaging to the glomerular capillaries. Arterial hypertension is not necessarily present before clinical nephropathy appears; however, it is a usual concomitant of progressive diabetic renal disease. The strongest evidences for the roles of altered systemic and renal hemodynamics in the progression of diabetic renal disease are clinical and experimental studies demonstrating attenuation of the disease process by lowering systemic and capillary pressures with antihypertensive agents, and dietary and glycemic modifications. Thus, although multiple factors probably interact to determine risk for the development of diabetic nephropathy, hemodynamic forces are a particularly important contributor and are especially amenable to therapeutic intervention.
Diabetes Care 1992 Sep
PMID:Diabetic nephropathy. Metabolic versus hemodynamic considerations. 139 17

Since gender can influence the renal toxicity of a drug in a given species, the present study was undertaken to evaluate the role of sex in the protection against gentamicin (G)-induced nephrotoxicity afforded by diabetes mellitus (DM) in the rat. We have compared the effects of administration of G (40 mg/kg/day, for 14 days) on male and female DM Sprague-Dawley rats. Non-diabetic animals of both sexes receiving identical doses of G served as controls. At the end of the experiment on day 14, both female (F) and male (M) control groups had similar and marked evidence of nephrotoxicity: elevation of plasma creatinine (F 1.7 +/- 0.7; M 2.8 +/- 0.6 mg/dl), decrease in endogenous 24-h creatinine clearance (Ccr) (F0.3 +/- 0.1; M 0.2 +/- 0.1 ml/min/100 g BW), and histological evidence of severe acute tubular necrosis. In marked contrast, the DM rats showed no functional or morphological evidence of renal damage throughout the study regardless of their gender (day 14: plasma creatinine: F 0.2 +/- 0.03; M 0.2 +/- 0.02; Ccr: F 1.2 +/- 0.1; M 1.6 +/- 0.1 ml/min/100 g BW), and they also accumulated less G in their kidney cortex than the C rats. The male controls exhibited higher renal cortex accumulation of G than the female controls (p < 0.05), whereas the opposite occurred in the DM groups (p < 0.01). Because the validity of using Ccr for the evaluation of GFR changes in experimental nephrotoxicity has been questioned, we have compared, in a separate experiment, three different methods of estimation of GFR (simultaneous short clearances of inulin and Ccr, and 24-h Ccr) in conscious female Sprague-Dawley rats undergoing the same treatment with G described above. At no time during the study did the method used for estimation of the GFR influence the results. We conclude that male and female Sprague-Dawley rats with diabetes are functionally and morphologically equally protected against G. Furthermore, no gender-related differences in the magnitude of G-induced nephrotoxicity was demonstrated in the non-diabetic control animals.
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PMID:The protection against gentamicin nephrotoxicity in the streptozotocin-induced diabetic rat is not related to gender. 143 83

The effects of early glycosylation products (Amadori Products, AP) were investigated in male Munich-Wistar rats to establish whether AP play a role in the pathogenesis of glomerular hyperfiltration of early diabetic nephropathy. To mimic such a condition, normal rats were transfused with blood containing in vitro glycated serum (Group GLYC) to achieve plasma levels of Amadori products similar to those measured in rats with streptozotocin-induced diabetes. Rats transfused with normal blood were used as control (Group CON). Glomerular hemodynamics was evaluated in basal condition (B) and during acute hyperglycemia (HG). Blood transfusion did not alter basal hemodynamics. In Group CON, HG determined a rise of single nephron GFR (41.4 +/- 3.2 vs. 32.1 +/- 1.8 nl/min, P less than 0.005), secondary to the increase of afferent effective filtration pressure (EFPa, +19% vs. B, P less than 0.01). Rats of Group GLYC, in B, had values of SNGFR higher than those of Group CON B (46.8 +/- 3 nl/min, P less than 0.05, ANOVA). This increase was mediated by a significant reduction of glomerular afferent arteriole (Ra, -38% vs. Group CON B, P less than 0.05), a rise in hydrostatic gradient pressure in glomerular capillaries (delta P, +17%, P less than 0.05) and of EFPa (+31%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early glycosylation products induce glomerular hyperfiltration in normal rats. 145 82

The offspring of essential hypertensive parents have been found to exhibit abnormalities in renal hemodynamics and sodium handling before the eventual occurrence of hypertension. The reported abnormalities represent a wide spectrum of changes including increased GFR, normal or decreased RPF, slight increase in blood pressure (although within the normal range), and an exaggerated natriuresis response to a sodium load. The heterogeneity of these abnormalities may reflect the specific conditions of the studies, the lability of the changes, or different subgroups of subjects with genetic predisposition to essential hypertension. Several lines of evidence have suggested a relationship between hypertension and the development of diabetic nephropathy in insulin-dependent diabetics. This laboratory has found that recent-onset insulin-dependent diabetics can exhibit renal hemodynamics abnormalities very early in the course of diabetes according to a positive or negative family history of essential hypertension. These changes include increased GFR and mean arterial pressure, but no differences in renal sodium and lithium handling in diabetics with a genetic predisposition to essential hypertension. In addition, diabetics with a positive family history of essential hypertension exhibited a more-marked vasodilative response to an acute interruption of the renin-angiotensin system, further suggesting inadequate angiotensin modulation of renal vascular tone. The significance of these abnormalities in relation to the development of diabetic nephropathy requires further investigation.
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PMID:Predisposition to essential hypertension and renal hemodynamics in recent-onset insulin-dependent diabetic patients. 145 59


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