Circadian rhythms of urinary electrolyte excretion in freely moving rats

In 8 freely moving rats the circadian variation in the eletrolyte excretion was studied. Food was available during either the dark or the light period. The lights were on from 0800–2000 hr. Potassium, phosphate and magnesium showed peak excretion values during the dark period under both feeding conditions, although the maxima occurred 2.5 hr earlier when the rats were fed during the light period; minimum excretion was recorded just prior to feeding. Sodium excretion followed a different pattern; for animals fed during the night, maximum excretion occurred almost at the end of the dark period and minimum excretion at the start of the feeding period. For day-fed animals these values were recorded 5 and 4 hours earlier, respectively. Calcium excretion reached a maximum after the feeding period and a minimum shortly after the onset of feeding. From this study it can be concluded that the peak excretions of potassium, phosphate and magnesium are only slightly influenced by the feeding regimen, indicating that they depend mainly on an endogenous rhythm. In contrast, the minimum excretion of these ions is determined by feeding. For calcium maximum as well as minimum excretion is correlated with the feeding regimen. The excretion pattern of sodium differs from that of calcium, as well as potassium, phosphate and magnesium, indicating that it is controlled by a different mechanism.     

Role of SCN in daily rhythms of plasma glucose, FFA, insulin and glucagon

The daily changes in plasma glucose, FFA, insulin and glucagon concentrations in rats under 12 hr-12 hr light-dark conditions, and the role of the suprachiasmatic nucleus (SCN) of the hypothalamus in these changes were examined. In sham-operated rats, the four parameters showed significant daily rhythms. However, after bilateral lesions of the SCN, daily rhythms could not be detected in these parameters under the present experimental conditions. Furthermore, after the SCN lesions the plasma glucose concentration remained at the minimum level of that in sham-operated rats, while the plasma insulin and glucagon concentrations reduced to approximately the mean level and about half the minimum level of sham-operated rats, respectively, and the FFA concentration lowered to somewhat below the minimum level. Gradual increase in the plasma insulin concentration at the end of the light period was observed in intact rats even after starvation for 24 hr. These findings suggest that the SCN is essential for generation of the daily changes in the plasma glucose, FFA, insulin and glucagon concentrations and also that it plays critical roles in regulation of the secretion of pancreatic hormones. The gradual increase in the plasma insulin level observed at the end of the light period is discussed in connection with initiation of spontaneous feeding behaviour.     

Role of SCN in Daily Rhythms of Plasma Glucose,FFA, Insulin and Glucagon

The daily changes in plasma glucose, FFA, insulin and glucagon concentrations in rats under 12 hr-12 hr light-dark conditions, and the role of the suprachiasmatic nucleus (SCN) of the hypothalamus in these changes were examined. In sham-operated rats, the four parameters showed significant daily rhythms. However, after bilateral lesions of the SCN, daily rhythms could not be detected in these parameters under the present experimental conditions. Furthermore, after the SCN lesions the plasma glucose concentration remained at the minimum level of that in sham-operated rats, while the plasma insulin and glucagon concentrations reduced to approximately the mean level and about half the minimum level of sham-operated rats, respectively, and the FFA concentration lowered to somewhat below the minimum level. Gradual increase in the plasma insulin concentration at the end of the light period was observed in intact rats even after starvation for 24 hr. These findings suggest that the SCN is essential for generation of the daily changes in the plasma glucose, FFA, insulin and glucagon concentrations and also that it plays critical roles in regulation of the secretion of pancreatic hormones. The gradual increase in the plasma insulin level observed at the end of the light period is discussed in connection with initiation of spontaneous feeding behaviour.     

Absence of Feeding-Induced Variations in Plasma Insulin in Hypoglycaemic-Ketonaemic Cows

The effects of food intake on plasma insulin levels were studied in 38 cows with plasma sugar ranging from 41 to 86 mg/100 ml and acetoacetate (Acac) ranging from 0.2 to 18 mg/100 ml, measured before morning feeding. The animals were fed concentrates, silage and hay. Blood samples were taken immediately before feeding in the morning and at intervals of % to 1 hr. during the following 4 hrs. In animals with low blood Acac, plasma insulin concentrations began to increase as early as 1/2 hr. after the start of feeding and reached maxima after 2 hrs. Simultaneously Acac increased and sugar decreased markedly. Animals with Acac levels > 1 mg/100 ml had low pre-feeding insulin concentrations, and the level of the hormone did not increase after feeding. They did not show systematic changes in Acac. But plasma sugar tended to decrease when food was given, even in the absence of insulin increments in peripheral blood. Glucose was infused at a low rate (0.9 g/min.) for 18 hrs. into a hypoglycaemic, ketonaemic cow. As her glucose and ketone levels became normalized, she also responded to feeding with insulin increments. But throughout the experiment her plasma insulin remained considerably lower than in an identically treated control animal which had low Acac levels before the infusion. It appears that the endocrine adjustments during ketonaemia in cows include, beside low basal (pre-feeding) insulin levels, an inhibition of the normally occurring elevation of plasma insulin after feeding.     

Cholecystokinins but not gastrin-17 release calcitonin from thyroid C-cells in the rat

Subcutaneous injections of gastrin-17, cholecystokinin-39, cholecystokinin-8 (sulfated and non-sulfated forms), cholecystokinin-4 or pentagastrin induced hypocalcemia in rats. The hypocalcemia was associated with calcitonin release for pentagastrin and the cholecystokinins but not for gastrin-17, even at very high doses. Permanent hypergastrinemia, induced by surgical removal of the acid-producing part of the stomach (fundectomy) or by treatment with high doses of omeprazole, a blocker of acid secretion, was not accompanied by elevated plasma calcitonin. Long-lasting hypergastrinemia is known to cause hyperplasia of gastrin-sensitive endocrine cells in the rat stomach while hypogastrinemia does the reverse. In antrectomized rats, having low serum gastrin, and in fundectomized rats, having high serum gastrin, the serum calcitonin concentration, the thyroid calcitonin content and the number of C-cells remained as in sham-operated controls two months after the operations. We conclude that neither exogenous nor endogenous gastrin stimulates calcitonin secretion in the rat and that long-standing hypo- or hypergastrinemia is without effect on the number of thyroid C-cells. Our results, however, do not exclude the possibility that the cholecystokinins might act as calcitonin secretagogues in the rat although such a role remains to be established.     

Adaptation of rainbow trout (Salmo gairdnerii) to sea water: Changes in calcitonin levels

• 1.1. The calcitonin content of the ultimobranchial body (UBB) and plasma levels of calcitonin, calcium and phosphate were measured in rainbow trout (Salmo gairdnerii) following their transfer from fresh to sea water.
• 2.2. The plasma calcium level remained unchanged throughout the experiment while the UBB calcitonin content, plasma calcitonin and plasma phosphate rose significantly during the hours immediately following transfer.
• 3.3. The levels of all three subsequently fall so that, 8–15 days later, a new equilibrium was established with lower than control (fresh water) levels of UBB calcitonin, plasma calcitonin and plasma phosphate.
• 4.4. It would appear, from these data, that calcitonin plays some part in the endocrine regulation of sea water transfer.

     

Time course changes in glycogen accretion, 6-phosphogluconate, fructose-2,6-bisphosphate, and lipogenesis upon refeeding a high sucrose diet to starved rats

1. Starved rats refed 60% sucrose diets were used to determine in vivo lipogenesis and levels of hepatic metabolites. 2. Fatty acid synthesis increased 11-fold 4 hr after refeeding. 3. Glycogen rose from 3 to 100 mg/g liver after 8 hr. 4. Fructose-2,6-bisphosphate rose to 6 nmol/g at 1 hr and remained constant. 5. 6-Phosphogluconate increased from 10 to 45 nmol/g liver after 2 hr and remained constant.     

Intestine, bone, and mammary gland contributions to maternal plasma calcium increase after abrupt weaning.

The response of maternal plasma calcium concentration to the abrupt and permanent removal of the suckling pups on Day 13 of lactation was investigated. Maternal plasma calcium did not change at 6 hr or 12 hr following pup removal. At 18 hr and 24 hr after weaning, the maternal plasma calcium concentration increased in mothers consuming either 0.47% calcium or 0.02% calcium diets. At 24 hr after weaning, the plasma calcium increase in mothers consuming low dietary calcium was 55% that of mothers consuming adequate dietary calcium. The contribution of the mammary gland to the plasma calcium increase in rats consuming the low dietary calcium was investigated by removing the mammary glands. Following mammary gland removal, plasma calcium increased 50% compared with mothers that had intact mammary glands. The data suggest that intestinal absorption of calcium and bone calcium mobilization remain stimulated by the lactation process for at least 24 hr after removal of the nursing pups.     

Neonatal chemical sympathectomy attenuates fructose-induced hypertriglyceridemia and hypertension in rats

Experiments were performed to determine the pathogenic contribution of the peripheral sympathetic nervous system to fructose-induced hypertriglyceridemia, hyperinsulinemia and hypertension in rats. Neonatal chemical sympathectomy was performed in neonatal Sprague-Dawley rats (1-week old) by administration of guanethidine (50 microg/g, i.p.) 5 times per week for consecutive 3 weeks and nerve-intact rats were served as controls. Both groups of rats were fed a fructose-enriched diet for 9 weeks. The systolic blood pressure (SBP) and body weight were measured weekly and arterial blood samples were taken weekly for determinations of plasma insulin, glucose and triglyceride levels. The results showed that fructose feeding for one week significantly increased SBP in intact rats and sympathectomized rats (116+/-1 to 119+/-1 mmHg and 116+/-1 to 120+/-1 mmHg, respectively). SBP further increased thereafter in both groups. However, the increased SBP levels were significantly higher in intact group than in sympathectomized group after 5 weeks of fructose feeding. Fructose feeding for one week concurrently produced hypertriglyceridemia that preceded the appearance of hyperinsulinemia in both groups. The elevated plasma triglyceride levels were significantly lower in sympathectomized rats than in intact rats after 3 weeks of fructose feeding, whereas the elevated plasma insulin concentrations were not different between groups throughout fructose feeding period. Plasma glucose concentrations of both groups were comparable and remained unchanged throughout the study. These data indicate that neonatal chemical sympathectomy attenuated, but did not prevent, fructose-induced elevations in blood pressure and plasma triglyceride levels, suggesting a partial dependency of fructose-induced hypertriglyceridemia and hypertension on the integrity of the peripheral sympathetic nervous system (SNS) in rats.     

Effect of infusion of salmon calcitonin on the secretion of somatostatin and gastrin in man

In vitro and animal studies have pointed out complex interrelations between gastrointestinal hormones and calcitonin. To analyse the acute effects of calcitonin in more detail, patients undergoing surgery were infused intravenously with synthetic salmon calcitonin, a potent analog of the human hormone. Samples were taken after 0, 30 and 60 minutes from the hepatic, portal and a peripheral vein. Somatostatin and gastrin were determined by radioimmunoassay. The mean basal levels of somatostatin in peripheral and hepatic venous plasma (14.2 and 15.6 pg/ml) were significantly lower than in portal plasma (45.6 pg/ml), indicating effective removal by the liver. After infusion of calcitonin there was a general rise in somatostatin levels and an increase in the gradient between hepatic and portal blood. Basal gastrin levels were highest in the portal vein when compared intraindividually. The differences disappeared after calcitonin infusion with a concomitant systemic reduction of gastrin levels. Thus, calcitonin is able to stimulate the secretion of somatostatin from the gastrointestinal tract and does reduce gastrin secretion, possibly via the stimulation of somatostatin secretion.     

Long-term effect of HCG on plasma testosterone in bulls.

The spontaneous diurnal variation of peripheral plasma testosterone concentrations in four bulls was established and then the long-term effect of a single intravenous or intramuscular injection of HCG on testosterone levels was studied. Intravenous and intramuscular HCG injections produced, within 1/2 hr and 3 hr, respectively, a rapid rise of testosterone to levels equivalent to the highest values seen in the diurnal pattern. A second increase of up to x2 to x3 the highest values of the diurnal cycle was observed 2 days after the injection of HCG, and the testosterone level remained high for at least 3 to 4 days after plasma levels of HCG were no longer detectable. The pattern of diurnal variation after HCG revealed an attenuation of the extensive spontaneous variation and high levels with only slight fluctuations were maintained.     

Plasma catecholamine and serum gastrin concentrations during sham feeding

Plasma adrenaline, plasma noradrenaline and serum gastrin concentrations were measured before and after sham feeding in eight patients with duodenal ulcer and in four normal subjects. No significant change in the concentrations was observed after sham feeding. In three patients with duodenal ulcer an insulin test resulted in a 25-fold rise in plasma adrenaline. The ulcer patients showed significantly higher levels of plasma adrenaline and plasma noradrenaline than the normal subjects both before and after sham feeding, and this difference was probably not caused only by age difference in the two groups. It is concluded that sympathetic nervous activity and serum gastrin concentrations are not influenced by sham feeding in contrast to the influence of insulin hypoglycemia.     

Dynamics of plasma Ca and calcitonin levels in stonefish (Inimicus japonicus) administered a high-Ca solution into the stomach

In stonefish, changes in plasma total Ca and calcitonin levels were examined after administration of a high-Ca solution into the stomach. Blood was taken successively at 0, 1, 3, 9, 33, and 81 hr from a fine tube cannulated into the aortic bulb. Plasma Ca levels increased acutely at 1 hr and attained the peak after 3-9 hr of the administration. Although plasma calcitonin levels did not exhibit conspicuous changes for 1-3 hr, they began to rise significantly at 33 hr. The plasma Ca level began to decline significantly at 33 hr, although the level was still significantly higher than the initial level. At 33 hr, however, the plasma calcitonin level still continued to increase. At 81 hr, the plasma Ca level had returned to the initial level. At that time, the plasma calcitonin level was also significantly lower than that at 33 hr. These results suggest that, in stonefish, the ultimobranchial gland has the ability to respond physiologically to rises in plasma Ca levels, to secrete calcitonin, and to cease the secretion when the plasma Ca levels return to the initial level.     

Circadian Assessment of Lipids in the Hyperphagic Obese Rat Compared with Lean Litter-Mates

Time and feeding influences on cholesterol, triglyceride, glucose and insulin levels, and serum cholinesterase activity were assessed in a genetically-hyperlipidemic hyperphagic obese rat model, and compared with its lean litter-mate. Following a 28-day acclimation to a 12-hr light/dark cycle, blood samples were obtained every 2 hr from rats via tail bleed for a 24-hr period. Synchronization with other animal studies was established by endogenous serum Cortisol levels [acrophase 18-20 hr after light onset (HALO) in both groups]. Triglycerides cholesterol, insulin and glucose levels were significantly elevated in obese versus lean rats. Obese rats were observed to feed throughout the 24-hr cycle, whereas lean litter-mates ate only during the dark cycle. No circadian rhythmicity was found in glucose levels with either rat group. Insulin levels were not correlated. Although triglyceride levels peaks at 13 HALO in lean rats, no pattern was observed in obese rats. Cholesterol levels were unchanged with time in either group. Cholinesterase activity followed a circadian rhythm in the lean, but not obese, rats with an acrophase estimated at 8 HALO. In contrast to previous reports, enzyme activity was not correlated with triglyceride levels in either rat group. Circadian similarities in insulin levels between rat groups suggest changes in insulin metabolism and/or secretion which are likely to be independent of feeding or activity. Conversely, triglyceride levels remained elevated throughout the 24-hr period in obese rats, whereas significant increases were observed in lean rats during the dark active cycle. These data suggest that triglyceride levels, and not insulin and cholesterol levels, are most likely dependent on feeding patterns.     

Circadian Assessment of Lipids in the Hyperphagic Obese Rat Compared with Lean Litter-Mates

Time and feeding influences on cholesterol, triglyceride, glucose and insulin levels, and serum cholinesterase activity were assessed in a genetically-hyperlipidemic hyperphagic obese rat model, and compared with its lean litter-mate. Following a 28-day acclimation to a 12-hr light/dark cycle, blood samples were obtained every 2 hr from rats via tail bleed for a 24-hr period. Synchronization with other animal studies was established by endogenous serum Cortisol levels [acrophase 18–20 hr after light onset (HALO) in both groups]. Triglycerides cholesterol, insulin and glucose levels were significantly elevated in obese versus lean rats. Obese rats were observed to feed throughout the 24-hr cycle, whereas lean litter-mates ate only during the dark cycle. No circadian rhythmicity was found in glucose levels with either rat group. Insulin levels were not correlated. Although triglyceride levels peaks at 13 HALO in lean rats, no pattern was observed in obese rats. Cholesterol levels were unchanged with time in either group. Cholinesterase activity followed a circadian rhythm in the lean, but not obese, rats with an acrophase estimated at 8 HALO. In contrast to previous reports, enzyme activity was not correlated with triglyceride levels in either rat group. Circadian similarities in insulin levels between rat groups suggest changes in insulin metabolism and/or secretion which are likely to be independent of feeding or activity. Conversely, triglyceride levels remained elevated throughout the 24-hr period in obese rats, whereas significant increases were observed in lean rats during the dark active cycle. These data suggest that triglyceride levels, and not insulin and cholesterol levels, are most likely dependent on feeding patterns.     

Effects of cold exposure on calcitonin secretion in the young rat

The effects of cold exposure on calcitonin (CT) secretion were evaluated in young rats. Acute cold exposure (5 h to 5 degrees C) induced a rise in plasma CT concentrations and a decrease in thyroidal CT stores without change in total and ionized plasma calcium levels. The cold activation of sympathico-adrenomedullary axis and the inhibition of CT response to cold after beta-antagonist treatment might suggest that endogenous catecholamines can enhance CT secretion in young rats. Cold adaptation (3 weeks to 5 degrees C) induced a fall in plasma calcium concentration and a rise in thyroidal CT stores without change in plasma CT levels. The high plasma glucocorticoid levels which are known to occur during chronic cold exposure could be involved in the rise of thyroidal CT content in cold adapted rats.     

Effect of 17 beta-estradiol and testosterone on guanosine 3', 5'-cyclic monophosphate in the rat adrenal cortex

The levels of guanosine 3′, 5′-cyclic monophosphate (cGMP) were measured in the rat adrenal cortex after administration of a single dose of either 17β-estradiol or testosterone. Young immature rats received 10 μg 17β-estradiol (females) or 100 μg testosterone (males). After testosterone administration, cGMP levels progressively rose to about 150 per cent of the control values after 4–6 hrs, and remained elevated until at least 9 hr. Administration of 17β-estradiol resulted in a similar increase in cGMP, which began at 2 hr and persisted until 9 hr, reaching levels of about 180 per cent of the controls. Our data are further evidence of general effect of steroid hormones on cGMP in their target tissues.     

Biological actions of human and rat calcitonin and calcitonin gene-related peptide

We assessed the central and peripheral biological actions of human and rat calcitonin and calcitonin gene-related peptide (CGRP). After intravenous administration, human and rat calcitonin, but neither human nor rat CGRP significantly decreased plasma calcium and phosphorus concentrations in awake, freely moving rats. After intracerebroventricular as well as after intravenous administration, human and rat calcitonin and human and rat CGRP significantly inhibited gastric acid secretion in conscious rats. Intracerebroventricular administration of rat calcitonin did not alter plasma calcium and phosphorus concentrations. Linear, partially protected CGRP and calcitonin did not exhibit any biological effects. These studies indicate that calcitonin, but not CGRP, affects calcium and phosphorus homeostasis while both peptides decrease gastric acid secretion similarly. Furthermore, these studies support the hypothesis that the calcium and phosphorus lowering effects of calcitonin are peripheral while the gastric inhibiting actions of the calcitonin and CGRP are mediated by the central nervous system.     

Effects of dexamethasone on the activity of histidine decarboxylase, ornithine decarboxylase, and dopa decarboxylase in rat oxyntic mucosa

Since accelerated turnover of histamine in oxyntic mucosa may be an important factor in the pathogenesis of peptic ulcers, the effect of dexamethasone and other glucocorticoids on the activity of gastric histidine decarboxylase (HDC) was studied in the rat. The activity of HDC in rat oxyntic mucosa increased significantly after dexamethasone was injected s.c. to rats at doses larger than 0.4 mg/kg body weight. The maximum response of the HDC activity to dexamethasone (4 mg/kg) was observed 8 h after the treatment. The activity of ornithine decarboxylase (ODC) increased at 4 h, while that of DOPA decarboxylase showed no significant change throughout the 16-h period following a single injection of dexamethasone. The mucosal levels of histamine, putrescine, and spermidine rose significantly after the steroid treatment, while the spermine levels remained nearly constant. There was no sex difference in these responses to dexamethasone. Betamethasone showed nearly the same effects as dexamethasone on the decarboxylase activities and the mucosal levels of diamines. Serum gastrin levels showed no significant change for the first 4 h and then rose significantly 8 and 16 h after dexamethasone treatment. Pentagastrin (0.5 mg/kg) increased the HDC activity, while it showed no significant effect on either the mucosal ODC activity or levels of polyamines and histamine. These data suggest that dexamethasone influences the metabolism of histamine and polyamines in rat oxyntic mucosa both directly and via stimulation of gastrin release.     

A transient increase in renal clearance of phosphate in response to continuous infusion of salmon calcitonin in rats.

The effects of intravenous carrier-free salmon calcitonin on renal clearances of phosphate, calcium, magnesium, sodium and potassium were studied in male parathyroid-ectomized (PTX) and intact rats. Both natural and synthetic hormone, when infused at constant rates (0.005 approximately 0.5 MRC U/hr), produced a rapid increase (peaking at about 60-90 min) in phosphate clearance. However, the maximal increase was transient in nature in PTX rats. In intact rats, the phosphaturic response was somewhat more pronounced and the decline after the peak was rather modest. When a large amount (4 MRC U) of calcitonin was given in divided doses, the second dose produced a lesser extent of phosphaturia in both intact and PTX rats. The phosphaturic response was accompanied by an increase in sodium and potassium clearances in PTX rats and by an increase in potassium clearance in intact rats. A fall in the apparent clearance values for calcium and magnesium occurred and was maintained throughout the infusion period of hormone in both intact and PTX rats. In conclusion, PTX rats respond to the intravenous administration of salmon calcitonin with a transient phosphaturic response which is accompanied by parallel diuresis of sodium and potassium along with sustained retention of calcium and magnesium by the kidney.