Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus

1988 ◽  
Vol 74 (6) ◽  
pp. 599-606 ◽  
Author(s):  
C. J. Thompson ◽  
S. N. Davis ◽  
P. C. Butler ◽  
J. A. Charlton ◽  
P. H. Baylis

1. Osmotically stimulated thirst and vasopressin release were studied during infusions of hypertonic sodium chloride and hypertonic d-glucose in euglycaemic clamped diabetic patients and healthy controls. 2. Infusion of hypertonic sodium chloride caused similar elevations of plasma osmolality in diabetic patients (288.0 ± 1.0 to 304.1 ± 1.6 mosmol/kg, mean ± sem, P < 0.001) and controls (288.6 ± 0.9 to 305.7 ± 0.6 mosmol/kg, P < 0.001), accompanied by progressive increases in plasma vasopressin (diabetic patients, 0.9 ± 0.3 to 7.7 ± 1.5 pmol/l, P < 0.001; controls 0.5 ± 0.1 to 6.5 ± 1.0 pmol/l, P < 0.001) and thirst ratings (diabetic patients 1.0 ± 0.2 to 7.1 ± 0.5 cm, P < 0.001; controls 1.8 ± 0.4 to 8.0 ± 0.5 cm, P < 0.001) in both groups. 3. Drinking rapidly abolished thirst and vasopressin secretion before major changes in plasma osmolality occurred in both diabetic patients and healthy controls. 4. There were close and significant correlations between plasma vasopressin and plasma osmolality (diabetic patients, r = + 0.89, controls r = + 0.93) and between thirst and plasma osmolality (diabetic patients r = +0.95, controls r = +0.97) in both diabetic patients and healthy controls during hypertonic saline infusion. 5. Hypertonic d-glucose infusion caused similar elevations in blood glucose in diabetic patients (4.0 ± 0.2 to 20.1 ± 1.2 mmol/l, P < 0.001) and healthy controls (4.3 ± 0.1 to 19.3 ± 1.2 mmol/l, P < 0.001) but did not change plasma vasopressin or thirst ratings. There was no correlation between plasma osmolality and either thirst or plasma vasopressin during hypertonic d-glucose infusion. 6. The characteristics of osmoregulated thirst and vasopressin release are similar in health and diabetes mellitus. As hyperglycaemia was not dipsogenic, however, the thirst of poorly controlled diabetes mellitus may be due to hypovolaemia secondary to polyuria rather than hyperosmolality due to elevated blood glucose concentrations.

1989 ◽  
Vol 256 (3) ◽  
pp. R597-R604 ◽  
Author(s):  
C. J. Thompson ◽  
S. N. Davis ◽  
P. H. Baylis

Poorly controlled insulin-dependent diabetes mellitus is associated with considerable elevations of plasma vasopressin concentrations, although well-controlled diabetics have normal osmoregulated thirst and vasopressin release. We studied the effect of blood glucose concentration on osmoregulated thirst and vasopressin secretion in insulin-dependent diabetes mellitus. Blood glucose was maintained overnight, and for the duration of the study, in either the euglycemic (4-5 mmol/l) or hyperglycemic (10-12 mmol/l) range, and patients underwent infusion of hypertonic (855 mmol/l) sodium chloride solution. Plasma sodium was lower during the hyperglycemic study, but elevation in plasma sodium concentration by infusion of saline caused progressive linear increases in both thirst and plasma vasopressin concentrations in both studies. Linear regression analysis defined lowered plasma sodium thresholds for both thirst appreciation and vasopressin release during the hyperglycemic study, although the sensitivity of the osmoreceptors remained unchanged. Analysis of the data in terms of plasma osmolality, corrected for the increase in blood glucose in the hyperglycemic study, revealed no differences in the osmotic thresholds for thirst or vasopressin release; sensitivity of the osmoreceptors also remained the same. Drinking abolished thirst and lowered plasma vasopressin concentrations before major changes in plasma sodium were observed. These results show that insulin-dependent diabetic patients osmoregulate appropriately when moderately hyperglycemic but that the threshold plasma sodium for vasopressin secretion and thirst appreciation is lowered by an unknown mechanism.


1985 ◽  
Vol 249 (3) ◽  
pp. E317-E325 ◽  
Author(s):  
R. L. Zerbe ◽  
F. Vinicor ◽  
G. L. Robertson

Patients with uncontrolled insulin-dependent diabetes mellitus have elevations in plasma vasopressin that cannot be accounted for totally by recognized osmotic or nonosmotic stimuli. To investigate the possibility that regulation of vasopressin secretion is abnormal in this disease, we characterized the vasopressin response to osmotic and hemodynamic stimuli in five uncomplicated, well-controlled insulin-dependent diabetics, and compared the results with those found in nondiabetic volunteers. During osmotic stimulation with hypertonic saline, plasma vasopressin increased in close linear correlation with plasma osmolality or sodium in both groups. However, in the diabetics, the lines describing the relationships between plasma sodium and vasopressin were shifted significantly to the left of normal, suggesting resetting of the osmostat. This shift was not due to abnormal stimulation by hyperglycemia, because increasing plasma glucose and osmolality by intravenous infusion of hypertonic dextrose produced no increase in plasma vasopressin in diabetics or normals. Tilt tests produced a slightly exaggerated increase in plasma vasopressin in diabetics, but their basal and upright pulse rate, blood pressure, plasma renin activity, norepinephrine, and hematocrit were all normal. The results indicate that in diabetic patients the osmoreceptor for osmotic regulation of vasopressin secretion is reset in such a way that higher plasma vasopressin levels are observed at comparable levels of plasma sodium. The exact cause and consequence of this abnormality remain to be determined.


1987 ◽  
Vol 252 (6) ◽  
pp. R1138-R1142 ◽  
Author(s):  
C. J. Thompson ◽  
J. M. Burd ◽  
P. H. Baylis

Drinking rapidly abolishes thirst and vasopressin secretion in dehydrated humans before major changes in plasma osmolality are observed. We studied the effects of drinking on plasma vasopressin and thirst in seven healthy volunteers rendered hypernatremic by the infusion of hypertonic (855 mmol/l) sodium chloride solution. Thirst was measured on a visual analogue scale (0-10 cm). Infusion of hypertonic saline caused linear increases in plasma osmolality (289 +/- 1 to 306 +/- 1 mosmol/kg, mean +/- SE, P less than 0.001), plasma vasopressin (0.6 +/- 0.2 to 6.4 +/- 1.9 pmol/l, P less than 0.001), and thirst (1.4 +/- 0.4 to 7.4 +/- 0.5 cm, P less than 0.001). Water was allowed 15 min after cessation of the infusion, and within 5 min of drinking both plasma vasopressin and thirst were significantly lower than postinfusion. After 20 min of drinking, plasma vasopressin had fallen from 6.5 +/- 0.9 to 1.3 +/- 0.3 pmol/l (P less than 0.001) and thirst from 7.7 +/- 0.5 to 1.0 +/- 0.2 cm (P less than 0.001) despite no significant change in plasma osmolality (306 +/- 0.9 to 304 +/- 0.8 mosmol/kg, P = 0.17), and the drinking of 1,200 +/- 60 ml of water, over 85% of the mean cumulative water intake in the 30-min drinking period. Control studies in the same subjects showed comparable rises in plasma vasopressin, plasma osmolality, and thirst during hypertonic saline infusion but no fall in any of these parameters during an equivalent 30-min period after the infusions, during which water was withheld.(ABSTRACT TRUNCATED AT 250 WORDS)


1987 ◽  
Vol 252 (4) ◽  
pp. E538-E548 ◽  
Author(s):  
T. P. Vokes ◽  
P. R. Aycinena ◽  
G. L. Robertson

Patients with uncontrolled insulin-dependent diabetes mellitus have elevations in plasma vasopressin that cannot be completely accounted for by recognized stimuli. To determine whether insulin deficiency per se increases plasma vasopressin, we investigated the effect of acute insulin depletion on the osmoregulation of plasma vasopressin in insulin-dependent diabetics. When intravenous insulin infusion was stopped, plasma vasopressin, osmolality, and glucose increased over the ensuing 5 h, whereas plasma sodium decreased, and blood volume and pressure did not change. This increase in vasopressin was not due to a loss of osmoregulation, because changes in plasma osmolality and sodium, induced by infusion of hypertonic saline or water loading, induced appropriate vasopressin responses under insulin deplete as well as replete conditions. However, when plasma osmolality and glucose were raised by infusion of hypertonic dextrose, plasma vasopressin increased significantly in diabetic patients under insulin-deplete but not under insulin-replete conditions and actually decreased in healthy controls. These results indicate that acute insulin depletion increases vasopressin secretion by sensitizing the osmoreceptor to stimulation by hyperglycemia. This change in osmoreceptor specificity may be explained by postulating that glucose transport by osmoreceptor neurons as insulin dependent.


1987 ◽  
Vol 253 (5) ◽  
pp. R671-R678 ◽  
Author(s):  
P. H. Baylis

The functional characteristics of osmoregulated vasopressin secretion can be defined in terms of an osmotic threshold for its release and a sensitivity of the osmoreceptor and vasopressin-secreting unit. Osmotically stimulated thirst has features similar to osmoregulated vasopressin. There are wide individual variations in the functional characteristics of both thirst and vasopressin release in healthy humans, probably genetic in origin. The influence of aging appears to enhance the sensitivity of vasopressin secretion but blunt thirst appreciation. Yet in many physiological situations changes in osmoregulated vasopressin release and thirst occur in parallel. The fall in plasma osmolality associated with human pregnancy is accounted for entirely by a lowering of the osmotic thresholds for thirst and vasopressin release. Similar but less marked alterations accompany the ovulatory luteal phase of the menstrual cycle. A major nonosmotic stimulus to vasopressin secretion is hypotension and/or hypovolemia, mediated by high- (carotid sinus) and low- (left atrial) pressure receptors. Circulating catecholamines influence the release of vasopressin by alpha- and beta-adrenergic pathways. Drinking by hypertonic humans provides immediate reduction in thirst and vasopressin secretion probably mediated by pathways from the oropharynx. The modest but variable rise in plasma vasopressin in response to hypoglycemia appears to be due to cellular neuroglycopenia and is independent of parasympathetic pathways. Although osmotic and hemodynamic stimuli to vasopressin release do not act independently of each other, the precise subtle interactions between them and other nonosmotic stimuli remain to be clarified.


1988 ◽  
Vol 116 (2) ◽  
pp. 217-224 ◽  
Author(s):  
M. L. Forsling ◽  
C. Matziari ◽  
L. Aziz

ABSTRACT The vasopressin response of rats to i.p. injection of hypertonic sodium chloride (1·5 mol/l) was compared with that following i.v. infusion of 1·05 mol sodium chloride/l. The two regimes produced a similar vasopressin response in terms of the osmotic threshold, although the slopes of the plot of plasma vasopressin levels against plasma osmolality were not identical. Pretreatment with naloxone and levallorphan increased the resting vasopressin levels and effectively potentiated vasopressin release in response to hypertonic saline by reducing the osmotic threshold for hormone release. Thus, opioid peptides appear to exert an inhibitory effect on vasopressin release under resting and stimulated conditions. The adrenoreceptor antagonists propanolol, phenyoxybenzamine and phentolamine produced a fall in resting vasopressin concentrations while propanolol and phenoxybenzamine potentiated the osmotic release of vasopressin in association with a fall in the osmotic threshold. This would suggest that noradrenergic pathways are excitatory at rest while having an inhibitory effect on the osmotic response. Metoclopramide also produced a fall in resting plasma vasopressin concentrations while increasing the osmotic response. In contrast haloperidol did not affect the vasopressin response. J. Endocr. (1988) 116, 217–224


1980 ◽  
Vol 73 (4) ◽  
pp. 255-260 ◽  
Author(s):  
P H Baylis ◽  
G L Robertson

Hypertonic saline was infused into 11 volunteers to osmotically stimulate vasopressin secretion. A strong positive correlation between plasma arginine vasopressin (PAVP) and plasma osmolality (Pos) was obtained, defined by the function PAVP = 0.63 (Pos – 284), r = +0.80, P < 0.001. The sensitivity of vasopressin secretion to osmotic stimulation was represented by the slope of the expression and the theoretical threshold of vasopressin release by the abscissal intercept. Plasma osmolality at the onset of thirst was 298.5 ± 1.1 mmol/kg. Application of hypertonic saline infusion to 10 polyuric patients clearly separated those with normal osmoregulation of vasopressin secretion from those with cranial diabetes insipidus.


1991 ◽  
Vol 260 (3) ◽  
pp. R533-R539 ◽  
Author(s):  
C. J. Thompson ◽  
P. Selby ◽  
P. H. Baylis

We have studied the reproducibility of the thirst and arginine vasopressin (AVP) responses to osmotic and hypoglycemic stimulation in healthy volunteers undergoing repeat hypertonic (855 mmol/l) saline infusion and insulin tolerance tests (ITTs). Hypertonic saline infusion caused similar mean rises in plasma osmolality, AVP, and thirst on each occasion. Linear-regression analysis defined close relationships between the slopes (r = +0.72, P less than 0.05) and the abscissal intercepts (r = +0.89, P less than 0.001) of the regression lines relating plasma osmolality (Posmol) and plasma AVP (PAVP), and the group intraindividual component of the variance for the slopes and intercepts was 7 and 0.6%, respectively. There were close correlations between the slopes (r = +0.79, P less than 0.02) and the intercepts (r = +0.84, P less than 0.01) of the regression lines relating Posmol and thirst, and group intraindividual component of the variance was 14 and 0.7%, respectively. Hypertonic saline infusion was infused on four occasions in four subjects, and the results showed that the linear regression lines relating PAVP and Posmol and thirst and Posmol were reproducible within an individual. There were similar falls in blood glucose and elevations in PAVP in both ITTs. No relationship was defined between the fall in blood glucose and either the rise in PAVP or the area under the AVP curve (AUC). The intraindividual component of the variance for the rise in AVP and the AUC was 77 and 22.5%, respectively. The AVP and thirst responses to osmotic stimulation are highly reproducible, but there is considerable intraindividual variation in the AVP response to hypoglycemia.


1988 ◽  
Vol 254 (4) ◽  
pp. R641-R647 ◽  
Author(s):  
T. J. Vokes ◽  
N. M. Weiss ◽  
J. Schreiber ◽  
M. B. Gaskill ◽  
G. L. Robertson

Changes in osmoregulation during normal menstrual cycle were examined in 15 healthy women. In 10 women, studied repetitively during two consecutive menstrual cycles, basal plasma osmolality, sodium, and urea decreased by 4 mosmol/kg, 2 meq/l, and 0.5 mM, respectively (all P less than 0.02) from the follicular to luteal phase. Plasma vasopressin, protein, hematocrit, mean arterial pressure, and body weight did not change. In five other women, diluting capacity and osmotic control of thirst and vasopressin release were assessed in follicular, ovulatory, and luteal phases. Responses of thirst and/or plasma vasopressin, urine osmolality, osmolal and free water clearance to water loading, and infusion of hypertonic saline were normal and similar in the three phases. However, the plasma osmolality at which plasma vasopressin and urine osmolality were maximally suppressed as well as calculated osmotic thresholds for thirst and vasopressin release were lower by 5 mosmol/kg in the luteal than in the follicular phase. This lowering of osmotic thresholds for thirst and vasopressin release, which occurs in the luteal phase, is qualitatively similar to that observed in pregnancy and should be taken into account when studying water balance and regulation of vasopressin secretion in healthy cycling women.


2020 ◽  
Vol 7 (4) ◽  
pp. 586
Author(s):  
Janak G. Chokshi ◽  
Apal P. Gandhi ◽  
Ishvarlal M. Parmar ◽  
Dipen R. Damor

Background: Diabetes mellitus (DM) is a syndrome consisting of metabolic, vascular and neuropathic components that are interrelated. Diabetes mellitus is associated with a considerably increased risk of premature atherosclerosis, particularly coronary heart disease (CHD) and peripheral arterial disease. Dyslipidemia is a common feature of diabetes. There is an association between atherosclerotic cardiovascular disease and serum cholesterol and triglyceride levels in both type 1 and type 2 diabetes.Methods: The study was done on 50 adult diabetes mellitus (T2) patients from IPD of General Medicine wards at SMS Hospital, Ahmedabad, Gujarat. 50 healthy age and sex matched healthy volunteers were taken as control. They were evaluated for lipid profile i.e., Total Cholesterol (TC),Triglyceride (TG), Low-density lipoprotein (LDL), High density lipoprotein (HDL), Very low density lipoprotein (VLDL) and glycemic status i.e., Fasting blood glucose (FBS), Postprandial 2 hours blood glucose (PP2BS) & Glycosylated haemoglobin(HbA1C).Results: Diabetic cases had statistically highly significant (p<0.001) elevated levels of total Cholesterol, Triglycerides and VLDL as compared to controls. Serum TG, serum TC, LDL-C and VLDL-C had positive correlation with the postprandial plasma glucose, fasting plasma glucose and HbA1c.Conclusions: Significant correlations between HbA1c levels and lipid levels point towards the usefulness of HbA1c for screening high-risk diabetic patients. High TC, TG, LDL-C and HbA1c with normal or low HDL-C is seen in almost all diabetic patients either alone or in combinations.


Sign in / Sign up

Export Citation Format

Share Document