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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To compare the long-term effectiveness of whole pancreas transplantation and pancreatic islet transplantation in controlling the metabolic disorders and preventing the kidney lesions of alloxan diabetes, metabolic and morphologic studies were performed in four groups of rats: (1) NC-116 nondiabetic controls; (2) DC-273 untreated alloxan-diabetic controls; (3) PDT-182 rats that received syngeneic pancreaticoduodenal transplants not long after induction of diabetes with alloxan; and (4) IT-92 rats that received an intraportal injection of at least 1500 and usually 2000 syngeneic pancreatic islets soon after induction of diabetes with alloxan. Each month for 24 months after diabetes was well established, body weight and plasma concentrations of glucose and insulin were measured, and five lesions were scored by light microscopy in 50 glomeruli and related tubules in each kidney by a "blind" protocol: glomerular basement membrane thickening, mesangial enlargement, Bowman's capsule thickening, Armanni-Ebstein lesions of the tubules, and tubular protein casts. There were progressive and highly significant increases in the incidence and severity of all five kidney lesions in the diabetic control rats compared with the nondiabetic control rats. No significant differences were found between the kidneys of Group PDT and those of Group NC, demonstrating that whole pancreas transplantation prevented all of the diabetic kidney lesions throughout the 2-year study period. In contrast, within 3-9 months after pancreatic islet transplantation and thereafter, the incidence and severity of the five diabetic kidney lesions were similar in Group IT and Group DC. Whole pancreas transplantation produced precise metabolic control of diabetes throughout the 24 months of study, whereas pancreatic islet transplantation did not accomplish complete metabolic control, particularly beyond the first several months after transplantation. The difference in the completeness of metabolic control achieved by the two types of transplants is the most likely explanation for their sharp difference in effectiveness in preventing diabetic nephropathy.
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PMID:Comparison of whole pancreas and pancreatic islet transplantation in controlling nephropathy and metabolic disorders of diabetes. 311 6

To compare the long-term effectiveness of whole pancreas transplantation and pancreatic islet transplantation in controlling the metabolic disorders of alloxan diabetes, metabolic studies were performed monthly for 2 years in 4 groups of highly inbred rats: (1) NC-116 nondiabetic controls; (2) DC-273 untreated alloxan-diabetic controls; (3) PDT-182 rats that received syngeneic pancreaticoduodenal transplants shortly after induction of diabetes with alloxan; and (4) IT-92 rats that received an intraportal injection of at least 1500, but usually 2000, syngeneic pancreatic islets shortly after induction of diabetes with alloxan. Whole pancreas transplantation maintained strict metabolic control throughout the 2 years of study. In group PDT, hyperglycemia was abolished; plasma glucose concentration was maintained tightly within the normal range; markedly depressed plasma insulin levels were raised to above normal; glucose tolerance tests had insulin levels above normal and glucose levels that increased less and declined more rapidly than normal; and body weight gain and growth approached normal. In contrast, pancreatic islet transplantation failed to maintain precise metabolic control. In group IT, plasma glucose concentration initially fell to normal but then was elevated significantly above normal beginning with the 3rd posttransplant month; plasma insulin level declined progressively after the 6th posttransplant month; glucose tolerance tests had a diabetic glucose tolerance curve as a result of a markedly deficient plasma insulin response; and body weight gain and growth were significantly less than in group PDT. The results of these long-term metabolic studies may explain the effectiveness of whole pancreas transplantation and the ineffectiveness of pancreatic islet transplantation in preventing diabetic nephropathy.
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PMID:Comparison of the metabolic control of diabetes achieved by whole pancreas transplantation and pancreatic islet transplantation in rats. 312 35

To determine whether pancreas transplantation is capable of preventing diabetic somatic neuropathy, metabolic studies and electron microscopic morphometry of the sciatic nerve were performed monthly for 2 years in four groups of highly inbred rats: (1) NC-28 nondiabetic controls; (2) DC-82 untreated alloxan-diabetic controls; (3) WPT-122 diabetic rats that received a syngeneic whole-pancreas transplant; and (4) IT-90 diabetic rats that received intraportal injections of 1500 to 2000 syngeneic pancreatic islets. Five diabetic nerve lesions were quantitated by a "blind" protocol: intra-axonal glycogen deposits, axons with glycogen deposits, demyelinated axons, intact axoglial junctions in paranodal terminal myelin loops, and basal lamina thickness of vasa nervorum. Untreated diabetic control animals had significant and progressive increases in all five nerve lesions compared to nondiabetic controls (p less than 0.01). Whole pancreas transplants produced precise metabolic control of diabetes and prevented development and progression of all five diabetic nerve lesions throughout the 2-year study period. Pancreatic islet transplantation produced strict metabolic control and prevented diabetic neuropathy for the first 6 months, but then diabetes recurred and nerve lesions that were similar in severity to those in untreated diabetic rats developed. The finding that whole pancreas transplantation prevents diabetic somatic neuropathy adds to and extends our previous studies showing that whole-pancreas transplants prevent diabetic nephropathy.
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PMID:Effect of pancreas transplantation on diabetic somatic neuropathy. 313 31

Elevated glomerular filtration rate (GFR) is a frequent finding in patients with early insulin-dependent diabetes mellitus (IDDM). The mechanisms responsible for this glomerular hyperfiltration in IDDM are unclear. Rats made diabetic with alloxan or streptozotocin, and treated daily with supplemental insulin, have moderate hyperglycemia and elevated GFR, and thus have been used to study mechanisms of glomerular hyperfiltration in diabetes. Renal micropuncture techniques have shown that single-nephron GFR (SNGFR) is elevated in moderately hyperglycemic diabetic rats. In some cases, this is because of elevated glomerular capillary pressure (Pgc), but in other cases, Pgc is normal despite elevated SNGFR. Several potential mediators of increased SNGFR have been examined, including hyperglycemia, increased glomerular prostaglandin production, and decreased sensitivity of the tubuloglomerular feedback mechanism. Renal failure is a common complication of human IDDM. Diabetic rats with long-term moderate hyperglycemia have been used to study the mechanism by which glomerular injury develops in diabetes mellitus. It has been postulated that glomerular hyperfiltration or some determinant of elevated GFR in early diabetes may ultimately cause glomerular damage, leading to a progressive loss of renal function (diabetic nephropathy). Diabetic rats with long-term moderate hyperglycemia, however, do not develop characteristic glomerular lesions of human diabetic nephropathy and, in fact, develop only minimal glomerular injury even after 1 year of diabetes. Thus, although the diabetic rat with moderate hyperglycemia may be useful to study the mechanisms of glomerular hyperfiltration in early diabetes, it may not be an appropriate model of renal failure in IDDM.
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PMID:Glomerular hemodynamic and structural alterations in experimental diabetes mellitus. 328 59

To evaluate the role of hyperglycemia in the pathogenesis of diabetic nephropathy, the kidneys from dogs experimentally galactosemic for 5 yr have been compared with the kidneys from age-matched normal dogs and dogs with alloxan-induced diabetes for 5 yr. The width of glomerular capillary basement membrane and the quantity of plasma protein immunohistochemically demonstrable in the basement membrane were supranormal in the galactosemics, as they were in the diabetics. In contrast, kidney weight, mesangial volume, and the prevalence of obliterated glomeruli, glomerular exudates, and mesangial nodules in the galactosemic animals were comparable to those of normal animals and clearly were less than observed in the insulin-deficient diabetic animals. These galactosemic dogs are known to have developed a retinopathy morphologically indistinguishable from that of diabetic patients and dogs. Thus, galactosemia sufficient to produce diabetic-like lesions in the glomerular basement membrane and retina was found to be nevertheless insufficient to elicit several renal abnormalities that are typical of diabetes. The polyol concentration in erythrocytes was greater than normal in the galactosemics and the diabetics and was greatest in the galactosemics. The absence of mesangial expansion, glomerular obliteration, and nephromegaly in galactose-fed dogs raises the possibility that these abnormalities in diabetes are not a result of excessive polyol pathway activity.
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PMID:Kidney morphology in experimental hyperglycemia. 380 34

After mentioning insulin deficiency diabetes in animals produced by drugs such as Alloxan, Diazoxide or Streptozotocin only drugs are discussed, which are used in elderly patients and may either provoke diabetes mellitus (or temporary hyperglycemia) or may change the clinical course of diabetes. In the first group endocrine products such as corticosteroids, estrogens, somatotrophic hormone, thyroid hormone, glucagon, somatostatin, catecholamines and hormones with anabolic effects are listed. The second group comprises saluretics, salicylates, amphetamines, pentamidine, nicotinic acid and its derivatives, beta-receptor blockers and finally laxatives. Hypopotassemia alone can also be the cause of hyperglycemia. Speaking of the sulfonylureapreparations, their interaction with alcohol, with phenylbutazone, with some sulfonamides and the effect of the sulfonylureas on peripheric insulin-receptors is discussed. In case of severe diabetic vascular disease the use of anticoagulants may lead to hemorrhages. If such an hemorrhage occurs in the eyes, it may lead to blindness. In diabetic nephropathy the use of phenacetine and its derivatives should be substituted by another medication. This review is not at all complete but should only show some of the problems in the treatment of elderly diabetic patients.
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PMID:[Iatrogenic diabetes mellitus (side effects and interactions of drugs during clinical diabetes mellitus (author's transl)]. 612 38

The study of diabetic nephropathy in experimental animals generally relies on the chemical induction of the diabetic state. Streptozotocin is commonly employed to that end; however, streptozotocin has an inherent nephrotoxic potential. We studied the effects of both streptozotocin, and diabetes on the kidneys of rats given streptozotocin 60 mg/kg, which was sufficient to induce severe diabetes. Our studies, which utilized both transmission and scanning electron microscopy, considered the pharmacokinetics of streptozotocin in renal tissue, as well as the effect of insulin treatment. Renal tissue kinetics were altered by occluding the renal hilum of one kidney during, and for 5 min after, the administration of streptozotocin. We found that, in contrast to alloxan, streptozotocin caused no detectable renal injury at the dose employed. Previously described renal epithelial papillomas were identified, and were not influenced by altering the renal tissue kinetics of the drug. We conclude that no 'protection' procedure is necessary for the kidney when the streptozotocin model of diabetes is employed. In this regard streptozotocin may have greater utility than alloxan.
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PMID:The effect of streptozotocin and streptozotocin-induced diabetes on the kidney. 623 4

It is now known that insulin has marked acute effects on plasma noradrenaline and the cardiovascular system. These effects of insulin are not due to hypoglycemia and occur without changes in plasma adrenaline. Intravenous injection of insulin in juvenile diabetics increased plasma noradrenaline and heart rate and decreased glomerular filtration rate, renal and peripheral blood flow, and plasma volume. Urinary excretion rates of beta-2-microglobulin and urinary volume decreased after insulin, whereas urinary albumin excretion increased. When blood glucose was maintained by glucose infusion after insulin, glomerular filtration rate and renal blood flow remained unaltered whereas plasma noradrenaline, heart rate, and urinary albumin excretion increased and beta-2-microglobulin excretion decreased. Decreases in glomerular filtration rate and renal blood flow after insulin are thus due to the fall in blood glucose. Rise in albumin excretion after insulin is probably of glomerular origin and not caused by the fall in blood glucose or by changes in renal hemodynamics. In patients with long-term diabetic nephropathy and albuminuria, insulin decreased albumin excretion (probably due to renal vasoconstriction) and plasma noradrenaline did not increase. In alloxan-diabetic rabbits the increase in heart rate after insulin was not abolished by autonomic blockade. In short-term streptozotocin-diabetic rats, muscle capillary endothelial cells showed a reduced number of free micropinocytotic vesicles. The number was nearly normalized 1 hr after intramuscular injection of insulin. The mechanism of action of insulin on plasma noradrenaline, heart rate, plasma volume, and urinary albumin excretion is not known. The rise in plasma noradrenaline after insulin may be compensatory to hypovolemia or to antagonizing effects of insulin on some actions of noradrenaline. The findings in streptozotocin-diabetic rats suggest that insulin may be essential for the normal function of capillary endothelial cells.
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PMID:Acute effects of insulin on plasma noradrenaline and the cardiovascular system. 700 Nov 80

The uptake of magnesium-28 was measured in slices of kidney cortex from rats with alloxan-diabetes and from rats with streptozotocin-diabetes of increasing durations. In both forms of chemically-induced diabetes, magnesium-28 uptake by kidney cortex slices was significantly increased over uptake measured in kidney cortex slices from control rats. Immediate institution of daily insulin therapy to the diabetic rats prevented the diabetes-induced elevated uptake of magnesium without controlling blood glucose levels. Late institution of daily insulin therapy was ineffective in restoring the magnesium uptake to control values. These alterations in magnesium uptake occurred prior to any evidence of nephropathy (via the classic indices of proteinuria and increased BUN levels). The implications of these findings, together with our earlier demonstrations of altered calcium transport by kidney cortex slices from chemically-induced diabetic rats, are discussed in terms of disordered divalent cation transport being at least part of the basic pathogenesis underlying diabetic nephropathy.
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PMID:Altered magnesium transport in slices of kidney cortex from chemically-induced diabetic rats. 703 10

Carefully age-matched, purebred male beagle dogs that underwent uninephrectomy one month after they were made diabetic with alloxan were used to establish a model of rapidly developing diabetic nephropathy in a large animal. The diabetic animals, all requiring insulin, were divided into two groups: one group with control by insulin injections permitting elevated fasting and postprandial serum glucose values and substantial glycosuria; the other with better control and with near-normal serum glucose levels and less glycosuria. By 1 year of diabetes both diabetic groups had renal lesions different from the uninephrectomized control animals but differing only slightly from one another. With light microscopy, diabetic dogs had increased mesangial thickening. With electron microscopic morphometry, glomeruli of diabetic subjects demonstrated increased fractional volumes of the total mesangium and of its cellular and matrix components and increased width of the GBM. These quantitative measures of diabetic nephropathy in the dog within 1 year of onset of the disease describe a model potentially useful in evaluating the efficacy of improved diabetic control in preventing or ameliorating diabetic nephropathy.
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PMID:Diabetic nephropathy in the uninephrectomized dog: microscopic lesions after one year. 705 May 10


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