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

In three patients with diabetes and hyporeninemic hypoaldosteronism changes in renin activity, plasma aldosterone and cortisol were examined under various conditions: orthostasis and intravenous furosemide, infusion of synthetic beta1-24 ACTH on two consecutive days and diurnal variations in basal hormone fluctuations. Each patient showed unmeasurably low renin activity unresponsive to orthostasis and intravenous furosemide while plasma aldosterone was below normal range. Under ACTH-infusion only marked increases in aldosterone were observed in one patient whereas cortisol responded normally in all diabetics tested. Analysis of diurnal night day fluctuations (20.00-8.00) in plasma aldosterone and cortisol revealed a close and statistically significant relationship between both hormones in each of the three patients (p less then 0.05-less than 0.001). Variations in plasma aldosterone thus were mediated through changes in endogenous pituitary ACTH. Compared with normal controls however, diurnal aldosterone curves were set at a lower level. Our results demonstrate that a reduced sensitivity of the adrenal gland to ACTH is not responsible for the observed subnormal plasma aldosterone levels in these patients. Therefore, the lack of circulating angiotensin II seems to be the causative reason of hypoaldosteronism. The exact mechanism of undetectable renin activity in these patients remains unknown.
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PMID:Control of plasma aldosterone in diabetic patients with hyporeninemic hypoaldosteronism. 20 28

Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2 x 2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2 x 2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.
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PMID:Inhibition of the renin-angiotensin-system in Brattleboro rats with hereditary hypothalamic diabetes insipidus. 21 21

In alloxan-treated diabetic rats, plasma renin activity (PRA) is decreased. One possible mechanism that may explain the decreased PRA is an increased delivery of sodium to the macula densa produced by the glucose osmotic diuresis, resulting in decreased renin release. To evaluate this possible mechanism, rats with phlorhizin diabetes, which produces a glucose osmotic diuresis without hyperglycemia, were studied and compared with rats with alloxan-induced diabetes. Whereas phlorhizin-treated rats had low blood glucose and alloxan-treated rats had elevated glucose, the glucose osmotic diuresis was similar in the two groups. PRA and plasma renin concentration (PRC) were significantly increased in the phlorhizin group. In the alloxan group, PRA was decreased and angiotensin II sensitivity increased, both significantly. Plasma renin substrate (PRS) remained adequate in each group. These results suggest that the decreased PRA in alloxan-induced diabetes is due neither to factors associated with the glucose osmotic diuresis including changes in renal tubular sodium not to decreased PRS.
Diabetes 1979 Feb
PMID:Renin-angiotensin system in phlorhizin compared with alloxan diabetes in the rat. 42 68

To investigate a possible action of insulin on the glomerulus, the binding 125I-insulin to the isolated glomeruli prepared from rat kidney was examined. When incubated at 22 degrees C, 125I-insulin binding proceeded with time and reached a steady state at 45 min at which time nonspecific binding was less than 25% of total binding. A small fraction of 125I-insulin was degraded during incubation. This binding was specific to insulin in that it was inhibited by unlabeled porcine and beef insulins and to a lesser extent by porcine proinsulin and desalanine-desasparagine insulin, but not by glucagon, parathyroid hormone, vasopressin, calcitonin, and angiotensin II. Increasing concentrations of nonlabeled insulin displaced 125I-insulin binding in a dose-dependent fashion. Scatchard plot of the data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that demonstrate negative cooperativity. The addition of excess nonlabeled insulin to the glomeruli preincubated with 125I-insulin resulted in a rapid dissociation of approximately or equal to 70% of bound 125I-insulin. Insulin decreased the increments in glomerular cyclic AMP levels by epinephrine and by prostaglandin E2, but not those by histamine. These data showed the presence of specific insulin receptors in the glomeruli, and that insulin action may be, at least in part, through modulation of glomerular cyclic AMP concentrations. Such action of insulin may underlie the alteration in glomerular ultrafiltration and the glomerular ultrafiltration and the development of glomerular lesions in diabetes mellitus, a disease in which insulin deficiency or the tissue resistance to insulin exists.
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PMID:Binding of 125I-insulin to the isolated glomeruli of rat kidney. 50 Aug 16

Vascular responsiveness to infused angiotensin II and to norepinephrine was determined in 14 normal subjects and two groups of diabetic subjects, 16 with no clinically detectable diabetic complications and 14 with diabetic retinopathy but no clinical evidence of nephropathy. All were maintained on a 100-mEq. -Na- 100-mEq. -K diet. Serum electrolytes, 24-hour urinary sodium, creatinine clearance, and plasma renin activity did not differ significantly among the groups. Group mean baseline diastolic pressure in those with retinopathy was higher than in normal subjects but no significantly different from that of uncomplicated diabetics. The pressor dose of angiotensin II (ng./kg./min. to increase diastolic blood pressure 20 mm. Hg) for each group respectively was 11.5 +/-0.9, 12.9+/- 1.3, and 8.3 +/- 1.3, and the slope of the dose-response curve (mm. Hg rise in blood pressure resulting from the infusion of 1 ng./kg./min. following the initial increment in blood pressure) was 2.0 +/-0.2, 1.6+/-0.2, 3.3+/- 0.6. For norepinephrine, the pressor doses were 163 +/- 24, 212+/-21, and123 +/- 11 and slopes were 0.17 +/- 0.03, 0.13 +/- 0.02, and 0.20 +/-0.02. Neither diabetic group differed significantly from normal subjects. Diabetics with retinopathy were more sensitive to angiotensin II, pressor dose (P less than 0.059) and slope (P less than 0.02), and to norepinephrine, pressor dose (P less than 0.006) and slope (P =0.05) than those without complications. These data suggest that vascular reactivity is enhanced in diabetics with retinopathy.
Diabetes 1976 Apr
PMID:Vascular reactivity to angiotensin II and to norepinephrine in diabetic subjects. 77 23

In the streptozotocin (STZ)-treated diabetic rat, reduced glomerular arteriolar resistance leads to raised intraglomerular pressure. Because vasoconstrictor hormones, such as angiotensin II, stimulate arteriolar smooth muscle and mesangial cell contraction via the D-myo-inositol (MI)-dependent transmembrane signaling pathway, in diabetes extracellular D-glucose may inhibit MI transport causing MI depletion, reduced signaling, and hypocontractility. Therefore we studied the regulation of Na-dependent MI transport in the intact cells (mesangial and endothelial) of isolated glomeruli from STZ rats after 2 wk of diabetes, with and without insulin, compared with controls. Specific [3H]MI uptake per milligram glomerular protein (10-150 min, 37 degrees C) was observed in the presence of 0, 5.5, and 30 mM D-glucose using L-[14C]glucose as a marker of nonspecific uptake. D-Glucose competitively inhibited Na-dependent MI transport (maximum velocity) into diabetic and normal glomerular cells. At 5.5 mM D-glucose, MI uptake by diabetic non-insulin-treated glomeruli was increased to 191 +/- 14% (SE) above normal glomeruli. Insulin treatment resulted in less upregulation (116 +/- 11%) of normal MI transport. High glucose concentration did not alter the rate of [3H]MI efflux from preloaded glomerular cells. To determine whether diabetes alters available substrate for transmembrane signaling, after incubation for 120 min, the incorporation of [3H]MI into cellular membrane phosphoinositides and soluble D-myo-inositol phosphates of isolated diabetic and control glomerular cells was compared. Diabetic glomerular cells displayed a significant increase (P less than 0.005) in [3H]MI incorporation into these fractions compared with controls.
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PMID:Upregulation of D-myo-inositol transport in diabetic rat glomerular cells. 131 87

Though long standing diabetes mellitus is frequently accompanied by hypoaldosteronism, the role of insulin in this setting has never been clearly established. In the present study we have examined the direct effects of insulin on aldosterone production in rat zona glomerulosa cells in vitro. Insulin is shown to directly stimulate aldosterone production in a dose dependent manner, and to attenuate angiotensin II mediated aldosterone production, without affecting angiotensin II receptor binding kinetics. Insulin had no effect on aldosterone production mediated by the other physiological stimuli (K+ and ACTH). These data suggest a possible interaction between insulin and angiotensin II in the regulation of aldosterone secretion.
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PMID:In vitro effects of insulin on aldosterone production in rat zona glomerulosa cells. 131 36

Growth or altered metabolism of nonmyocyte cells (cardiac fibroblasts, vascular smooth muscle and endothelial cells) alters myocardial and vascular structure (remodeling) and function. However, the precise roles of circulating and locally generated factors such as angiotensin II, aldosterone and endothelin that regulate growth and metabolism of nonmyocyte cells have yet to be fully elucidated. Trials of pharmacologic therapy aimed at preventing structural remodeling and repairing altered myocardial structure to or toward normal in the setting of hypertension, heart failure and diabetes are reviewed. It is proposed that these are therapeutic goals that may reduce cardiovascular morbidity and mortality. Although this hypothesis remains unproved the primary goal of therapy should be to preserve or restore tissue structure and function.
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PMID:Remodeling and reparation of the cardiovascular system. 131 86

1. Diabetes mellitus was induced by streptozotocin in male Wistar rats, and angiotensin-converting enzyme measured in plasma and mesenteric vessels 3 weeks later. 2. Diabetes was associated with increased mesenteric wet weight/bodyweight ratio (control 0.2 s.e.m. 0.02 mg/g, n = 21, vs diabetes 1.0 s.e.m. 0.3 mg/g, n = 27, P less than 0.01, ANOVA). 3. Plasma angiotensin-converting enzyme activity was increased in diabetic rats (98 s.e.m. 3 nmol HL/mL per min) compared with controls (64 s.e.m. 6 nmol HL/mL per min, P less than 0.01, ANOVA). 4. Mesenteric vessel angiotensin-converting enzyme was increased in diabetes mellitus estimated by radioligand binding site density (fmol/mg protein; 1407 s.e.m. 166 fmol/mg protein) compared with controls (890 s.e.m. 56 fmol/mg protein, P less than 0.05, ANOVA) and by enzyme kinetic assay (diabetes, 15.5 s.e.m. 1.5 nmol HL/mg protein per min, controls, 8.3 s.e.m. 0.7 nmol HL/mg protein per min, P less than 0.01, ANOVA). The equilibrium dissociation constant of ligand-angiotensin-converting enzyme interaction was unchanged. 5. Increased vascular angiotensin-converting enzyme concentration may contribute to vascular hypertrophy and diabetic vasculopathy by increased local synthesis of angiotensin II.
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PMID:Mesenteric vascular angiotensin-converting enzyme is increased in experimental diabetes mellitus. 132 83

1. In order to investigate the modulation of kidney function in insulin-dependent diabetes mellitus, intraindividual variation in glomerular filtration rate, renal plasma flow, urinary albumin excretion rate and mean arterial blood pressure was assessed in 22 normoalbuminuric patients [age 31 +/- 8 years, duration of diabetes 9 +/- 5 years, mean arterial blood pressure 90 +/- 5 mmHg (means +/- SD), urinary albumin excretion rate 5.4 x/divided by 1.6 micrograms/min]. The variation in these parameters was calculated from the results of two clearance studies (continuous infusion of [125I]-iothalamate and 131I-hippuran as markers for glomerular filtration rate and renal plasma flow, respectively) and was subsequently analysed in relation to individual variation in plasma concentrations of atrial natriuretic peptide, arginine vasopressin, angiotensin II and aldosterone and measures of glycaemic control. 2. Simple correlation analysis showed a significant association between intra-individual variation in glomerular filtration rate and atrial natriuretic peptide (sigma = 0.66, P = 0.003). Besides variation in atrial natriuretic peptide, multiple regression analysis identified variation in glycated haemoglobin (P = 0.026) and arginine vasopressin (P = 0.057) as variables having independent association with variation in glomerular filtration rate [R2 with the three variables included (adjusted for degrees of freedom) = 0.50, analysis of variance: P = 0.002]. 3. With respect to variation in renal plasma flow, differences in fasting blood glucose concentration and mean arterial blood pressure were suggested as determinants (R2 = 0.36, analysis of variance: P = 0.009). 4. Variation in urinary albumin excretion rate (after log transformation) was statistically associated with variation in glycated haemoglobin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determinants of intra-individual variation in kidney function in normoalbuminuric insulin-dependent diabetic patients: importance of atrial natriuretic peptide and glycaemic control. 133 Apr 7


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