Impaired sodium excretion in response to volume expansion induced by water immersion in insulin-dependent diabetes mellitus

1986 ◽  
Vol 71 (4) ◽  
pp. 403-409 ◽  
Author(s):  
J. P. O'Hare ◽  
J. M. Roland ◽  
G. Walters ◽  
R. J. M. Corrall

1. The renal response to volume expansion produced by water immersion to the neck at 35°C was examined in eight young normotensive uncomplicated insulin-dependent diabetic subjects and in eight matched normal control subjects. 2. Both the diabetic and normal subjects manifested a renal response of natriuresis and kaliuresis on immersion, but the natriuretic response was reduced in the diabetic group. Thus the induced excretion of sodium over the 4 h of immersion was 40 ± 5 mmol (mean ± sem) in the normal group compared with 22 ± 4 mmol in the diabetic group (P < 0.02). 3. In the normal subjects creatinine clearance did not change during immersion compared with pre-immersion control values while in the diabetic group it rose from pre-immersion control values of 112 ± 11 ml/min to a mean value of 127 ± 11 ml/min during immersion (P < 0.01). 4. The diabetic subjects thus excreted less sodium despite an increased filtered load during water immersion. Fractional excretion of sodium was significantly reduced in the diabetic subjects compared with the normal control subjects (P < 0.05). 5. The suppression of plasma renin and aldosterone was similar in normal and diabetic groups. 6. Tubular sodium retention could be an early functional change in the diabetic kidney, and be implicated in the development of diabetic nephropathy.

2020 ◽  
Vol 21 (3) ◽  
pp. 919 ◽  
Author(s):  
Maria Schindler ◽  
Sophia Mareike Pendzialek ◽  
Katarzyna Grybel ◽  
Tom Seeling ◽  
Anne Navarrete Santos

Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan treatment in female rabbits 10 days before mating. On day 6 post-coitum, plasma and blastocoel fluid (BF) were analysed by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) (Metabolon Inc. Durham, NC, USA). Metabolic datasets comprised a total of 284 and 597 compounds of known identity in BF and plasma, respectively. Diabetes mellitus had profound effects on maternal and embryonic metabolic profiles, with almost half of the metabolites changed. As predicted, we observed an increase in glucose and a decrease in 1,5-anhydroglucitol in diabetic plasma samples. In plasma, fructose, mannose, and sorbitol were elevated in the diabetic group, which may be a way of dealing with excess glucose. In BF, metabolites of the pentose metabolism were especially increased, indicating the need for ribose-based compounds relevant to DNA and RNA metabolism at this very early stage of embryo development. Other changes were more consistent between BF and plasma. Both displayed elevated acylcarnitines, body3-hydroxybutyrate, and multiple compounds within the branched chain amino acid metabolism pathway, suggesting that lipid beta-oxidation is occurring at elevated levels in the diabetic group. This study demonstrates that maternal and embryonic metabolism are closely related. Maternal diabetes mellitus profoundly alters the metabolic profile of the preimplantation embryo with changes in all subclasses of metabolites.


1983 ◽  
Vol 104 (4) ◽  
pp. 468-474 ◽  
Author(s):  
Mitsuyasu Itoh ◽  
Yoshifumi Hirooka ◽  
Noriyuki Nihei

Abstract. To study the role of somatostatin in the pathophysiology of glucose intolerance in man, plasma somatostatin-like immunoreactivity (SLI) was measured in 8 normal subjects, 6 patients with insulin dependent diabetes mellitus (IDDM), 13 with non-insulin dependent diabetes mellitus (NIDDM), and 9 with hyperthyroidism, by extraction of plasma SLI and radioimmunoassay. The extraction method gave a recovery rate for synthetic somatostatin-14 and somatostatin-28 of 72 ± 6 and 55 ± 7%, respectively. No SLI corresponding to somatostatin-28 in human peripheral blood was observed. Incubation of somatostatin-28 in plasma gave a rapid decrease of immunoreactivity, and no conversion to somatostatin-14 was observed. It is speculated that SLI extracted with acid-acetone mainly represents a molecular weight similar to somatostatin-14. After oral administration of glucose (75 g), a clear and sustained rise in plasma SLI was seen in normal subjects from an initial value (± sem) of 29.9 ± 5.4 pg/ml to a peak value, at 60 min of 93.4 ± 15.5 pg/ml. The increase of plasma SLI after 75 g glucose was also observed in IDDM and NIDDM. The peak level of SLI was significantly less than that for normal subjects. The extraction of plasma SLI with acetic acid and acetone gave reproducible results and showed a fluctuation of SLI with glucose concentration.


1983 ◽  
Vol 244 (4) ◽  
pp. R481-R486 ◽  
Author(s):  
G. G. Krishna ◽  
G. M. Danovitch

The renal response to central volume expansion induced by head-out water immersion was examined in 10 normal, salt-replete subjects studied during the day (0900–1300) and during the night (0000–0400). Sodium excretion in the hour preceding the study was 155 +/- 21 mueq/min and 120 +/- 14 mueq/min, respectively. During the day, immersion was followed by a natriuresis, which reached a mean peak level of 293 +/- 46 mueq/min during the 2nd h of immersion and which was maintained for the remainder of the immersion. During the night, there was no significant increase in sodium excretion from prestudy values during the first 3 h of immersion. Values rose significantly in the 4th h and reached a mean peak level of 211 +/- 20 mueq/min. Potassium excretion rose during the day (from 61 +/- 12 mueq/min to 126 +/- 16 mueq/min) but was unaltered at night. Neither glomerular filtration rate nor plasma levels of aldosterone differed between day and night. To exclude the possibility that the blunted nocturnal natriuresis could be explained by a lesser degree of central fluid translocation induced by immersion at night six normal salt-replete subjects received a 2-liter infusion of normal saline administered over 4 h during the day and during the night. The blunting of the nocturnal natriuresis was again observed. We conclude that, in addition to well-described diurnal variations in electrolyte excretion, there are diurnal variations in the responsivity of volume regulatory mechanisms.


1980 ◽  
Vol 59 (1) ◽  
pp. 55-62 ◽  
Author(s):  
M. Epstein ◽  
M. D. Lifschitz ◽  
R. Re ◽  
E. Haber

1. The relationship of the renin-angiotensin-aldosterone axis with renal prostaglandin E is complex. Although studies have suggested that these two hormonal systems respond to experimental manipulations in a parallel manner, their interdependence has not been assessed fully during volume expansion. Since studies have demonstrated that in normal man the central hypervolaemia induced by water immersion to the neck produces a prompt and profound suppression of plasma renin activity and plasma aldosterone concentration without concomitant alteration of plasma composition, immersion afforded a unique opportunity to assess simultaneously the effects of central hypervolaemia on plasma renin activity, plasma aldosterone concentration and prostaglandin E excretion. 2. Seven normal subjects were studied twice while in balance on a diet containing 10 mmol of sodium/day, 100 mmol of potassium/day: with indomethacin administration (50 mg given every 6 h for five doses) and without indomethacin. Urinary prostaglandin E excretion was measured hourly and plasma renin activity and plasma aldosterone concentration at 30 min intervals. 3. Immersion was associated with a marked suppression of plasma renin activity (59 ± 7%) and plasma aldosterone concentration (55 ± 3%) with a return to pre-study values during the recovery hour. Concomitantly, urinary prostaglandin E excretion increased from 4.7 to a peak of 10.9 ng/min. Although administration of indomethacin lowered the basal rate of urinary prostaglandin E excretion and plasma renin activity, it did not prevent the subsequent augmentation of urinary prostaglandin E or the suppression of plasma renin activity and plasma aldosterone during the subsequent 4 h of immersion. 4. These results demonstrate a dissociation of renin-aldosterone and prostaglandin E during hypervolaemia and suggest that whereas prostaglandin E may constitute one of the major determinants of renin release clinically and experimentally, these two hormonal systems can be dissociated from each other in response to central volume expansion in man.


1996 ◽  
Vol 91 (5) ◽  
pp. 567-573 ◽  
Author(s):  
G. F. Watts ◽  
S. F. O'brien ◽  
W. Silvester ◽  
J. A. Millar

1. We measured endothelium-dependent and independent dilatation of forearm resistance arteries in 29 men with diet-treated non-insulin-dependent diabetes mellitus and 18 age- and sex-matched control subjects. None of the diabetic patients had hypercholesterolaemia, overt hypertension or microproteinuria. 2. We examined endogenous and exogenous nitric oxide-mediated vasodilatation by measuring forearm blood flow with venous occlusive plethysmography after administration of acetylcholine (7.5 and 15 μg/min) and sodium nitroprusside (3 and 10 μg/min), respectively, into the brachial artery. NG-monomethyl-l-arginine was also infused to study the inhibition of basal and stimulated release of nitric oxide. 3. The vasodilatory response to acetylcholine, expressed as area under curve, was significantly decreased in the diabetic patients compared with the control subjects (P = 0.019). NG-monomethyl-l-arginine significantly reduced basal (P < 0.001) and acetylcholine-stimulated blood flow (P < 0.02) in both groups. The vasodilatory response (also expressed as area under curve) to sodium nitroprusside was significantly less (P = 0.044) in the diabetic patients than in the control subjects. 4. In the diabetic patients, impaired vasodilatory responses to acetylcholine were significantly correlated with higher serum triacylglycerols (P = 0.048) and lower high-density lipoprotein-cholesterol concentrations (P = 0.007); the association with high-density lipoprotein was independent of age, glycated haemoglobin and blood pressure. Sodium nitroprusside responses were not correlated with lipid and lipoprotein concentrations. 5. We conclude that there is impaired endothelial and smooth muscle cell function in men with diet-treated non-insulin-dependent diabetes mellitus uncomplicated by overt hypertension or microproteinuria. Endothelial dysfunction may be related to diabetic dyslipidaemia and associated metabolic disturbances.


1993 ◽  
Vol 75 (5) ◽  
pp. 2217-2223 ◽  
Author(s):  
J. A. Arrowood ◽  
J. Kline ◽  
P. M. Simpson ◽  
R. J. Quigg ◽  
J. J. Pippin ◽  
...  

During exercise, as heart rate (HR) increases, the QT interval of the electrocardiogram shortens. The mechanism(s) involved in this QT shortening has not been clearly defined. To distinguish the influence of increased circulating catecholamines from myocardial efferent stimulation, the relationship between HR and QT interval was investigated during exercise and cardiovascular reflex stimulation in cardiac transplant patients and normal control subjects. Because of cardiac denervation, increases in HR in these patients are solely due to circulating catecholamines and thus allow isolation of their effect on the QT interval. Twenty-one cardiac transplant patients were studied and compared with 16 normal control subjects. The QT-HR relationship was determined according to an exponential model during treadmill exercise in both groups [QT = 0.12 + 0.492e(-0.008.HR) and QT = 0.12 + 0.459e(-0.007.HR) in normal subjects and transplant patients, respectively] and was statistically similar between groups, suggesting similar QT interval shortening in both groups. During cold pressor and Valsalva maneuvers, HR increased significantly in normal subjects only, whereas QT interval changed minimally in both groups. These results suggest that during exercise the QT interval is influenced predominantly by increases in circulating catecholamines rather than by neurally mediated reflex autonomic changes.


2004 ◽  
Vol 286 (4) ◽  
pp. R751-R755 ◽  
Author(s):  
Daiyi Tang ◽  
Tianzheng Yu ◽  
Ali A. Khraibi

Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown to play a critical role in mediating sodium and water excretion under various conditions. The objective of this study was to determine the effects of immediate and delayed initiation of insulin treatment on the restoration of the relationship between RIHP, natriuretic, and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups of female Sprague-Dawley rats were studied: normal control group (C), untreated diabetic group (D), immediate insulin-treated diabetic group (DI; treatment with insulin for 2 wk was initiated immediately when diabetes was confirmed, which was 2 days after STZ injection), and delayed insulin-treated diabetic group (DDI; treatment with insulin for 2 wk was initiated 2 wk after STZ injection). RIHP and sodium and water excretions were measured before and during VE (5% body wt/30 min) in the four groups of anesthetized rats. VE significantly increased RIHP, fractional excretion of sodium (FENa), and urine flow rate (V) in all groups of rats. Basal RIHP, RIHP response to VE (ΔRIHP), and FENa and V responses to VE (ΔFENa and ΔV) were significantly lower in the D group compared with the C group of rats. ΔRIHP was significantly higher in both DI and DDI groups compared with D group but was similar to that of the C group of rats. While in the DI group the ΔFENa response to VE was restored, ΔFENa was significantly increased in DDI compared with D group, but it remained lower than that of the C group. In conclusion, insulin treatment initiated immediately after the onset of diabetes restores basal RIHP and RIHP, natriuretic, and diuretic responses to VE; however, delayed insulin treatment restores the basal RIHP and RIHP response to VE but does not fully restore the natriuretic response to VE.


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