Changes in plasma glucagon, pancreatic polypeptide and insulin during development of alloxan diabetes mellitus in dog

Changes in canine plasma glucose, immunoreactive glucagon (IRG), pancreatic polypeptide (PP) and insulin (IRI) were studied during the acute development of diabetes mellitus after iv alloxan injection. 100 mg or 75 mg/kg body weight of alloxan was injected iv and blood was taken successively till one or two days later. Plasma glucose showed four phases: first immediate and moderate decrease appeared 30 min after injection, second initial hyperglycemic phase, third hypoglycemic and fourth diabetic ones. Plasma IRI had already increased to 182 +/- 60 microU/ml 10 min after injection and again began to increase after about 6 h, peaking to 134 +/- 49 microU/ml at 18 h. Plasma IRG began increasing gradually soon after alloxan injection. The initial value was 196 +/- 26 pg/ml and it increased to 534 +/- 144 pg/ml at 4 h during the initial hyperglycemic phase, then reached a higher level through the hypoglycemic and diabetic phases. The change in plasma PP was similar to that in IRG. The initial value was 256 +/- 95 pg/ml at 12 h after injection, peaking to 840 +/- 100 pg/ml in the hypoglycemic phase. Similar blunted values were obtained following 75 mg/kg alloxan injection. Thus not only plasma IRI but also plasma IRG and PP varied greatly during the acute development of alloxan diabetes and some contribution of IRG to the initial hyperglycemic phase was suggested.     

Plasma glucagon-immunoreactive components in early life in dogs

High plasma concentrations of C-terminal immunoreactive glucagon (IRG) have been found during early life in several mammalian species. We have analyzed the plasma IRG of 12 h to 60 day-old dogs in terms of the 4 peaks (IRG greater than 20,000, IRG9000, IRG3500 and IRG2000) obtained by gel filtration on Bio-Gel P-30. Significant changes with age and in response to administered agents were confined to IRG9000 and IRG3500. IRG9000 was 9-fold higher in 12-36 h old dogs than in adults (108 +/- 24 pg/ml pancreatic glucagon equivalents v. 12 +/- 3 pg/ml, mean +/- SEM) and showed a decline to 2-fold higher (27 +/- 5 pg/ml) at 31-60 days. IRG3500 was higher than in the adult only during the first 36 h of life (36 +/- 5 pg/ml v. 15 +/- 3 pg/ml). Arginine infusion (0.5 g/kg over 15 min) caused an increase in plasma levels of both IRG9000 and IRG3500 in the newborn, whereas in adult dogs only IRG3500 was increased. Insulin injection (0.2 U/kg intravenously) causing a marked hypoglycemia had no significant effect on the plasma level of any IRG component in newborn dogs. Dihydrosomatostatin infusion (10 micrograms/kg bolus +/- 90 micrograms/kg over 30 min) caused a decrease in both IRG9000 and IRG3500. The increased basal level and secretory response to arginine of IRG9000 in newborn dogs may reflect an immaturity of the A cells, whereby more of this component, which may represent a precursor of pancreatic glucagon, is secreted than in the adult. The immature A cells also appear to have an impaired secretory response to hypoglycemia.     

Important role of glucagon during exercise in diabetic dogs

To define the role of immunoreactive glucagon (IRG) during exercise in diabetes, 12 insulin-deprived alloxan-diabetic (A-D) dogs were run for 90 min (100 m/min, 12 degrees) with or without somatostatin (St 0.5 microgram . kg-1 . min-1). Compared with normal dogs, A-D dogs were characterized by similar hepatic glucose production (Ra), lower glucose metabolic clearance, and higher plasma glucose and free fatty acid levels during rest and exercise. In A-D dogs IRG was greater at rest and exhibited a threefold greater exercise increment than controls, whereas immunoreactive insulin (IRI) was reduced by 68% at rest but had similar values to controls during exercise. Basal norepinephrine, epinephrine, cortisol, and lactate levels were similar in normal and A-D dogs. However, exercise increments in norepinephrine, cortisol, and lactate were higher in A-D dogs. When St was infused during exercise in the A-D dogs, IRG was suppressed by 432 +/- 146 pg/ml below basal and far below the exercise response in A-D controls (delta = 645 +/- 153 pg/ml). IRI was reduced by 1.8 +/- 0.2 microU/ml with St. With IRG suppression the increase in Ra seen in exercising A-D controls (delta = 4.8 +/- 1.6 mg . kg-1 . min-1) was virtually abolished, and glycemia fell by 104 to 133 +/- 37 mg/dl. Owing to this decrease in glycemia, the increase in glucose disappearance was attenuated. Despite the large fall in glucose during IRG suppression, counterregulatory increases were not excessive compared with A-D controls. In fact, as glucose levels approached euglycemia, the increments in norepinephrine and cortisol were reduced to levels similar to those seen in normal exercising dogs. In conclusion, IRG suppression during exercise in A-D dogs almost completely obviated the increase in Ra, resulting in a large decrease in plasma glucose. Despite this large fall in glucose, there was no excess counterregulation, since glucose concentrations never reached the hypoglycemic range.     

Rates of removal of exogenous and endogenous glucagon from the plasma of sheep in vivo

The removal of exogenous and endogenous glucagon from plasma was determined in vivo in sheep weighing 53 +/- 1 (mean +/- s.e.) kg. Porcine glucagon was infused intravenously for 90 min. The metabolic clearance rates (MCR) were determined from plateau immunoreactive glucagon (IRG) concentrations in plasma and infusion rates of glucagon. The mean clearance rate (+/0 s.e.) was 16.7 +/- 1.6 litres per hour (n = 20). Upon termination of the infusion, the decrease in IRG concentrations in plasma was determined. Least-squares regression analysis of non-linear functions indicated the data fit a two-component exponential function. The time constant for the rapid component of the plasma IRG disappearance function was -0.32 +/- 0.04 min-1 (mean +/- s.e.). The time constant for the slow component was -0.22 +/- 0.008 min-1. The rate of removal of endogenous glucagon was estimated during the infusion of somatostatin when glucagon secretion was inhibited. The time constants (mean +/. s.e., n = 8) for the decrease in IRG during somatostatin infusion were -0.42 +/- 0.08 and -0.003 +/- 0.002 min-1 for fast and slow components, respectively. The time constants for the rapid components of exogenous and endogenous glucagon were not significantly different. This suggests that endogenous and exogenous glucagon are similarly removed from plasma.     

Effect of hematocrit reduction on hormonal and metabolic responses to exercise

We wished to determine the effect of a 25% hematocrit reduction on glucoregulatory hormone release and glucose fluxes during exercise. In five anemic dogs, plasma glucose fell by 21 mg/dl and in five controls by 7 mg/dl by the end of the 90-min exercise period. After 50 min of exercise, hepatic glucose production (Ra) and glucose metabolic clearance rate (MCR) began to rise disproportionately in anemics compared with controls. By the end of exercise, the increase in Ra was almost threefold higher (delta 15.1 +/- 3.4 vs. delta 5.2 +/- 1.3 mg X kg-1 X min-1) and MCR nearly fourfold (delta 24.6 +/- 8.8 vs. delta 6.5 +/- 1.3 ml X kg-1 X min-1). Exercise with anemia, in relation to controls resulted in elevated levels of glucagon [immunoreactive glucagon (IRG) delta 1,283 +/- 507 vs delta 514 +/- 99 pg/ml], norepinephrine (delta 1,592 +/- 280 vs. delta 590 +/- 155 pg/ml), epinephrine (delta 2,293 +/- 994 vs. delta 385 +/- 186 pg/ml), cortisol (delta 6.7 +/- 2.2 vs. delta 2.1 +/- 1.0 micrograms/dl) and lactate (delta 12.1 +/- 2.2 vs. delta 4.2 +/- 1.8 mg/dl) after 90 min. Immunoreactive insulin and free fatty acids were similar in both groups. In conclusion, exercise with a 25% hematocrit reduction results in 1) elevated lactate, norepinephrine, epinephrine, cortisol, and IRG levels, 2) an increased Ra which is likely related to the increased counterregulatory response, and 3) we speculate that a near fourfold increase in MCR is related to metabolic changes due to hypoxia in working muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of subcutaneous pancreatic tissue transplants on streptozotocin-induced diabetes in rats. II. Endocrine and metabolic functions.

The present study examines the effect of subcutaneous pancreatic tissue grafts (SPTG) on endocrine and metabolic functions in streptozotocin (STZ)-induced diabetic rats using radioimmunoassay and biochemical techniques. SPTG survived even after 15 weeks of transplantation and significantly improved the weight of STZ-diabetic rats over a 15-week period. Although blood glucose-, cholesterol-, and glycosylated-haemoglobin (GHb) levels were not significantly lower in STZ-diabetic rats treated with SPTG, the values of these biochemical parameters were lower than those in untreated diabetic rats. Plasma and pancreatic immunoreactive C-peptide (IRCP) levels did not improve after SPTG (IRCP expressed as mean +/- standard deviation were 0.22 +/- 0.07, 0.072 +/- 0.02 and 0.08 +/- 0.03 pg ml-1 in the plasma non-diabetic diabetic and treated rats respectively, while IRCP levels in the pancreas of the non-diabetic, diabetic and treated rats were 433.8 +/- 0.1, 22.9 +/- 0.01 and 10.4 +/- 0.01 pg mg tissue-1 respectively). SPTG, however, improved plasma immunoreactive insulin (IRI) levels in both plasma and pancreas. IRI values in plasma were 54.7 +/- 13.6, 18.0 +/- 5.0 and 22.1 +/- 4.3 microUI ml-1 in non-diabetic, diabetic and treated rats respectively and were 277.3 +/- 37.1, 14.7 +/- 1.8 and 30.3 +/- 15.9 microIU micrograms tissue-1 in the pancreas of non-diabetic, diabetic and treated rats respectively. There was improvement in immunoreactive glucagon (IRG) levels after SPTG. IRG values in the plasma of non-diabetic, diabetic and treated rats were 147.0 +/- 10.7, 408.0 +/- 76.5 and 247.7 +/- 3 pg ml-1 respectively whereas, IRG measured in the pancreas was 1642.25 +/- 424.23, 1899.0 +/- 290.4 and 1714.1 +/- 301.98 pg micrograms tissue-1 in non-diabetic, diabetic and treated rats, respectively. The pancreas:plasma ratio of pancreatic hormones was deranged in untreated diabetes but improved after SPTG. In conclusion, SPTG significantly improved the weight gain, pancreatic insulin content, plasma IRG and pancreas: plasma ratio of IRCP, IRI and IRG. It also reduced blood glucose-, cholesterol-, and glycosylated-hemoglobin levels in STZ-diabetic rats.     

Response of plasma somatostatin-like immunoreactivity to the administration of alloxan in dogs.

The present study was designed to examine the effects of intravenously injected alloxan (75 mg/kg) upon plasma somatostatin-like immunoreactivity (SLI), glucagon (IRG), insulin (IRI) and glucose levels in 6 dogs. Within 2 hours of the injection of alloxan, SLI and IRI levels decreased significantly below their respective baselines, while IRG and plasma glucose concentrations increased. At 8 hours SLI levels had increased significantly by 55 pg/ml, together with a rise in IRI and a decrease in IRG and glucose concentrations. After 24 hours, marked hyperglycemia and hyperglucagonemia had developed whereas SLI levels were not different from preinjection values.     

Effect of phenformin on the response of plasma intestinal glucagon-like immunoreactivity (GLI) to oral glucose in gastrectomized subjects.

The effect of phenformin (DBI) on the plasma intestinal glucagon-like immunoreactivity (GLI) and pancreatic glucagon (IRG) responses to oral and intravenous glucose loads were studied in 26 gastrectomized subjects, using a cross-reacting and an IRG-specific anti-serum. The drug produced no significant changes in fasting GLI and IRG levels. Thirty minutes after oral glucose alone, the total GLI level rose to a peak of 1.55 +/- 0.17 ng/ml in the untreated subjects and to a maximum level of 1.67 +/- 0.18 ng/ml in the DBI-pretreated subjects. However, the mean GLI levels obtained 120 and 180 min after oral glucose were significantly higher after treatment with DBI. The blood sugar and IRI responses to oral glucose were lowered significantly by DBI pretreatment. DBI did not alter the glucose, IRI, IRG and GLI response to intravenous glucose. These results suggest that the release of intestinal GLI is not related to the intestinal absorption of glucose.     

Lack of effect of thyrotropin-releasing hormone (TRH) on the peripheral plasma levels of pancreatic glucagon in man

Based on the fact that human pancreas has thyrotropin-releasing hormone (TRH) immunoreactivity and bioactivity, we studied the effect of TRH on peripheral plasma levels of pancreatic glucagon (IRG) and insulin (IRI) in healthy subjects. During the infusion of 400 micrograms TRH for 120 min basal plasma IRI and IRG levels did not change significantly. In addition, intravenous infusion of 400 micrograms TRH did not affect the increments in the plasma IRG levels and the decrements in the blood glucose during insulin hypoglycemia.     

Pancreatic glucagon secretion during a short period of hemorrhage in anesthetized dogs

Glucagon has been implicated in the hormonal metabolic response to hemorrhage. However, evidence for this has been obtained largely from observations of circulating plasma glucagon concentration. A clear increase in the pancreatic glucagon secretion remains to be demonstrated. Plasma concentrations of pancreatic immunoreactive glucagon (IRG) and insulin (IRI) were determined in portal venous and aortic blood, and plasma glucose in aortic blood. Dogs were bled (approximately 15 mL/kg) until aortic systolic blood pressure dropped to approximately 50% (70.5 +/- 8.1 mmHg, n = 7) (1 mmHg = 133.32 Pa) of its control value (135 +/- 7.1 mmHg, n = 7), and the hemorrhagic hypotension was maintained for 10 min. The net portal venous IRG delivery rate rose significantly and continued to increase during the hemorrhagic hypotension despite a significant fall in the portal venous blood flow. Aortic IRG increased significantly along with the increase in portal venous IRG delivery rate (r = 0.838, n = 42, p less than 0.01). The portal venous delivery rate of IRI decreased significantly in response to hemorrhage. The aortic IRG/IRI concentration ratio increased significantly during the hemorrhage-induced hypotension. Aortic glucose concentration increased significantly 5 min after hemorrhage and continued to rise until the end of the hemorrhagic hypotension. The present study demonstrates that the secretion of pancreatic glucagon actually increases during the early phase of hemorrhage. The results also indicate that the increase in aortic IRG during the hemorrhagic hypotension is due to the increased pancreatic glucagon secretion. It is suggested that the pancreatic glucagon may be involved in the early hyperglycemic response to hemorrhage.     

Epinephrine infusion during moderate intensity exercise increases glucose production and uptake

The glucoregulatory response to intense exercise [IE, >80% maximum O(2) uptake (VO(2 max))] comprises a marked increment in glucose production (R(a)) and a lesser increment in glucose uptake (R(d)), resulting in hyperglycemia. The R(a) correlates with plasma catecholamines but not with the glucagon-to-insulin (IRG/IRI) ratio. If epinephrine (Epi) infusion during moderate exercise were able to markedly stimulate R(a), this would support an important role for the catecholamines' response in IE. Seven fit male subjects (26 +/- 2 yr, body mass index 23 +/- 0.5 kg/m(2), VO(2 max) 65 +/- 5 ml x kg(-1) x min(-1)) underwent 40 min of postabsorptive cycle ergometer exercise (145 +/- 14 W) once without [control (CON)] and once with Epi infusion [EPI (0.1 microg x kg(-1) x min(-1))] from 30 to 40 min. Epi levels reached 9.4 +/- 0.8 nM (20x rest, 10x CON). R(a) increased approximately 70% to 3.75 +/- 0.53 in CON but to 8.57 +/- 0.58 mg x kg(-1) x min(-1) in EPI (P < 0.001). Increments in R(a) and Epi correlated (r(2) = 0.923, P 相似文献   

Effect of intra-ovarian infusion of oxytocin on plasma progesterone concentrations in pregnant ewes.

The function of oxytocin receptors in the corpus luteum of pregnant ewes was investigated by infusing saline or oxytocin (100 ng/min) into the utero-ovarian artery of pregnant ewes (62 +/- 5 days, n = 12). During a 4-h infusion, plasma oxytocin (OT) concentration increased to 268 +/- 80 pg OT/ml in the OT-infused group and remained unchanged at 2.5 +/- 1.5 pg OT/ml in the saline-infused group. Progesterone concentration in jugular venous plasma (17 +/- 9 ng/ml) rapidly decreased during oxytocin infusion to 59 +/- 10% and 26 +/- 9% of control at 1.5 and 2 h, respectively; the utero-ovarian venous concentration of 64 +/- 38 ng/ml decreased by a similar magnitude during oxytocin infusion. Electron microscopy of corpora lutea, removed at the end of the experiments, showed no indication of luteolytic changes following oxytocin infusion. It was concluded that oxytocin markedly and rapidly reduces progesterone secretion in pregnant ewes.     

Acute angiotensin II increases plasma F2-isoprostanes in salt-replete human hypertensives

Angiotensin (Ang) II induces oxidative stress in vitro and in animal models of hypertension. We tested the hypothesis that Ang II increases oxidative stress in human hypertension, as assessed by plasma F2-isoprostane concentrations. Plasma F2-isoprostanes, hemodynamic and endocrine parameters were measured at baseline and following a 55 min infusion of 3 ng/kg/min Ang II in 13 normotensive and 13 hypertensive volunteers ingesting a high- (200 mmol/d) or low- (10 mmol/d) sodium diet. Mean arterial pressure (MAP) and body mass index were higher in hypertensive subjects. Ang II infusion increased MAP (p<.001) and plasma aldosterone concentrations (p<.001) and decreased plasma renin activity (p<.001) and renal plasma flow (p<.001) to a similar extent in both groups. Plasma F2-isoprostane concentrations were similar at baseline. There was no effect of Ang II on F2-isoprostane concentrations during low-salt intake in either group (normotensive 51.7 +/- 7.1 to 53.7 +/- 6.5 pg/ml and hypertensive 52.2 +/- 8.2 to 56.2 +/- 10.0 pg/ml; mean +/- SE). During high-salt intake, Ang II increased F2-isoprostane concentrations in the hypertensive group (52.3 +/- 7.2 to 63.2 +/- 10.4 pg/ml, p=0.010) but not in the normotensive group (54.2 +/- 4.4 to 58.9 +/- 6.6 pg/ml, p=0.83). Acute Ang II infusion increases oxidative stress in vivo in hypertensive humans. The renin-angiotensin system may contribute to oxidative stress in human cardiovascular disease.     

Plasma somatostatin in normal subjects and in various diseases: increased levels in somatostatin-producing tumors

The plasma levels of somatostatin (SRIF) were studied in normal subjects and patients with various disorders by a sensitive and specific radioimmunoassay. In 45 normal subjects, the fasting plasma SRIF concentrations were 13.3 +/- 5.3 pg/ml (mean +/- SD). Very high concentrations of plasma SRIF, ranging from 125.0 pg/ml to 400.0 pg/ml, were found in all four patients with medullary carcinoma of the thyroid examined and the SRIF levels were changed in parallel with their clinical course after resection of the tumor. A case of pheochromocytoma also showed a relatively high SRIF concentration in plasma (47.0 pg/ml), but the plasma SRIF level decreased to 8.7 pg/ml after removal of the tumor. In normal subjects, plasma SRIF levels did not fluctuate during 2 hr-observation period in basal state. Glucagon (1 mg, iv) and secretin (3 CHRU/kg B.W., iv infusion over 30 min) had no effect on the SRIF levels in the peripheral blood plasma of normal subjects. On intravenous infusion of arginine (0.5 g/kg B.W.) over 30 min, all 6 normal subjects showed a significant increase in plasma SRIF 30-45 min after the start of the infusion (basal value, 11.6 +/- 1.5 pg/ml; peak value, 27.2 +/- 3.0 pg/ml; p less than 0.005). Two cases of medullary thyroid carcinoma showed exaggerated responses after the arginine administration (increases of 103 pg/ml and 157 pg/ml, respectively), suggesting that SRIF was released from the tumor. The findings indicate that plasma SRIF determination in the basal state and after arginine administration is useful for detecting and following up SRIF-producing tumors.     

Identification and partial characterization of gonadotropin-releasing hormone-like factors in human seminal plasma

Gonadotropin-releasing hormone (GnRH)-like material was measured by radioimmunoassay in acid-ethanol-extracted human seminal plasma using radiolabeled D-[Leu6] GnRH ethylamide as labeled ligand, authentic GnRH as standard, and antibody raised against D-[Lys6] GnRH analog. The mean amount of GnRH-like material measured in the seminal plasma of semen samples with sperm counts greater than 20 X 10(6)/ml was 229.0 +/- 66 pg/ml, with sperm counts less than 20 X 10(6)/ml was 213 +/- 42 pg/ml, and from vasectomized samples was 252 +/- 36 pg/ml. There was no significant difference among the three groups. Scatchard analysis of radioreceptor binding data demonstrated significant displacement of GnRH agonist ligand from castrated male rat pituitary membrane preparations. Ultrafiltration and gel column chromatography of pooled extracted seminal plasma identified two compounds with apparent molecular weights of 2600 and 5000 that differ chemically and immunologically from native GnRH. Further characterization using affinity column chromatography suggests that at least one of these GnRH-like factors is a glycosylated protein.     

Fluid volume and osmoregulation in humans after a week of head-down bed rest

Body fluid homeostasis was investigated during chronic bed rest (BR) and compared with that of acute supine conditions. The hypothesis was tested that 6 degrees head-down BR leads to hypovolemia, which activates antinatriuretic mechanisms so that the renal responses to standardized saline loading are attenuated. Isotonic (20 ml/kg body wt) and hypertonic (2.5%, 7.2 ml/kg body wt) infusions were performed in eight subjects over 20 min following 7 and 10 days, respectively, of BR during constant sodium intake (200 meq/day). BR decreased body weight (83.0 +/- 4.8 to 81.8 +/- 4.4 kg) and increased plasma osmolality (285.9 +/- 0.6 to 288.5 +/- 0.9 mosmol/kgH(2)O, P < 0.05). Plasma ANG II doubled (4.2 +/- 1.2 to 8.8 +/- 1.8 pg/ml), whereas other endocrine variables decreased: plasma atrial natriuretic peptide (42 +/- 3 to 24 +/- 3 pg/ml), urinary urodilatin excretion rate (4.5 +/- 0.3 to 3.2 +/- 0.1 pg/min), and plasma vasopressin (1.7 +/- 0.3 to 0.8 +/- 0.2 pg/ml, P < 0.05). During BR, the natriuretic response to the isotonic saline infusion was augmented (39 +/- 8 vs. 18 +/- 6 meq sodium/350 min), whereas the response to hypertonic saline was unaltered (32 +/- 8 vs. 29 +/- 5 meq/350 min, P < 0.05). In conclusion, BR elicits antinatriuretic endocrine signals, but it does not attenuate the renal natriuretic response to saline stimuli in men; on the contrary, the response to isotonic saline is augmented.     

Relaxin regulates oxytocin secretion in late-pregnant beef heifers

The effects of porcine relaxin (3000 units/mg) on oxytocin (OT) and progesterone secretion were studied in beef heifers on Day 274 (10 days before expected parturition). Heifers (n = 11) were randomly assigned to three treatments: relaxin iv infusions combined with im injection (RLX-INF, 9000 units), relaxin im injection (RLX-im, 6000 units), and phosphate-buffered saline-treated controls (PBS). RLX-INF heifers received infusions of PBS and 1000 units of relaxin for 165 min, followed by 2000 units of relaxin im and finally 2000 units of relaxin infusion followed by 4000 units of relaxin im. Endogenous relaxin (immunoreactive) in the PBS-treated group was 0.2-0.9 ng/ml peripheral plasma. For the RLX-im group, peak relaxin was 81 +/- 12 ng/ml (+/- SE) at 45 min after treatment. There were two peaks of relaxin, 18 +/- 5.3 ng/ml and 74 +/- 7.5 ng/ml, 3.5-4.5 hr apart in the RLX-INF group. Significant peak releases of OT were evident in the relaxin-treated heifers. For the RLX-im group, an OT peak (42 +/- 16 pg/ml) occurred within 30 min after relaxin treatment. For the RLX-INF heifers, 2000 and 4000 units of relaxin were associated with major peaks of 14 +/- 0.5 and 43 +/- 1.7 pg/ml OT, respectively. Basal OT plasma levels in the PBS group were 2.5-3.1 pg/ml. Mean plasma progesterone for all heifers was 6.2 +/- 2.11 ng/ml before treatment. There was a significant decrease in progesterone (-2.5 ng/ml) in the RLX-im group within 60 min after relaxin treatment and 45 min after peak OT secretion. The maximum decrease in progesterone (-3.2 +/- 0.68 ng/ml) occurred 135 min after treatment in the RLX-im group. In the RLX-INF group, 2000 units of relaxin infusion combined with 4000 units of relaxin im significantly decreased progesterone (-3.2 +/- 1.59 ng/ml) in peripheral plasma. These results clearly indicate that relaxin causes an acute peak release of oxytocin within 30 min, followed by a marked decrease in plasma progesterone concentration in late-pregnancy cattle.     

Atrial natriuretic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man.

Corticotrophic secretion of ACTH is stimulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and suppressed by glucocorticoids. In vitro and preclinical studies suggest that atrial natriuretic factor (ANF) may be a peptidergic inhibitor of pituitary-adrenocortical activity. The aim of this study was to elucidate a possible role of ANF as a modulator of ACTH release in humans. A bolus injection of 100 micrograms human CRH (hCRH) during a 30 min intravenous infusion of 5 micrograms/min human alpha atrial natriuretic factor (h alpha ANF) was administered at 19:00 to six healthy male volunteers. In comparison to saline, a blunted CRH-stimulated secretion of ACTH (mean maximum plasma level +/- SD 45 min after hCRH: saline 46.2 +/- 14.2 pg/ml, h alpha ANF 34.6 +/- 13.8 pg/ml, p-value = 0.007) and a delayed rise (10 min) in cortisol were detected. The maximum plasma cortisol levels remained nearly unchanged between saline and h alpha ANF administration (mean maximum plasma level +/- SD 60 min after hCRH: saline 182 +/- 26 ng/ml, h alpha ANF 166 +/- 54 ng/ml). No effects of h alpha ANF on basal cortisol levels were observed; in contrast, basal ACTH plasma levels were slightly reduced. Basal blood pressure and heart rate remained unaffected. In the control experiment, infusion of 3 IU AVP in the same experimental paradigm increased basal and stimulated ACTH and cortisol levels significantly in comparison to saline. These observations suggest that intravenously administered haANF inhibits the CRH-stimulated release of ACTH in man.     

The effect of insulin-induced hypoglycaemia on the secretion of glucagon and hepatic glucose production in pancreatectomized dogs

The concentration of plasma glucose in insulin deprived pancreatectomized dogs was decreased from the basal 385 +/- 44 to 65 +/- 12 mg/dL by the infusion of 7 mU X kg-1 X min-1 insulin. During the infusion, the plasma concentration of immunoreactive glucagon (IRG) did not change and hepatic glucose production was decreased. This is in contrast to earlier findings in alloxan diabetic dogs in which plasma IRG decreased in hypoglycaemia. The hypothesis is put forward that, in contrast to pancreatic alpha cells in which the effect of insulin prevails, neither insulin nor a decrease in the ambient concentration of glucose exerts any effect on the secretion of glucagon from extrapancreatic alpha cells.     

Running and shipping elevate plasma levels of beta-endorphin-like substance (B-END-LI) in thoroughbred horses

A specific RIA for beta-endorphin (B-END) was developed to measure horse plasma levels of B-END-like material (B-END-LI) during exercises and shipping. Three exercise speeds and durations were: trot at 260-300 m/min for 10 min; slow gallop at 390-420 m/min for 5 min and fast gallop at 700-800 m/min for 2 min. Blood samples were taken from 4 horses before, immediately after, 30 and 60 min after exercise. Trotting increased plasma B-END-LI from a basal level of 109 +/- 7 pg/ml to 172 +/- 22 at the end of exercise and returned to 127 +/- 17 and 107 +/- 10 pg/ml at 30 and 60 min after exercise. Similar results were obtained in slow gallop (121 +/- 6 to 210 +/- 17 then 155 +/- 8 and 131 +/- 11 pg/ml). However, fast gallop caused the greatest increase (352%) in B-END-LI to concentrations of 544 +/- 93 pg/ml and 276 +/- 74 pg/ml at 5 and 30 min after exercise. Plasma B-END-LI returned to 199 +/- 46 pg/ml in 1 hr. Sequential exercises of trot, slow and fast gallop were conducted in 6 horses. Plasma B-END-LI were 116 +/- 19 pg/ml (pre-exercise), 198 +/- 21 (trot), 361 +/- 51 (slow gallop), 500 +/- 57 (fast gallop) and 248 +/- 29, 171 +/- 24, 143 +/- 20 and 139 +/- 21 pg/ml at 0.5, 1, 2 and 3 hr, respectively, following exercises. Transportation in horse trailer also significantly increased plasma levels of B-END-LI from a basal level of 138 +/- 12 to 196 +/- 24 pg/ml within 30 min and this levels were maintained at 45 min (177 +/- 3 pg/ml). Plasma levels of B-END-LI began to decline at 60 min of shipping. These results showed that plasma B-END-LI was increased in all speeds of exercise and by shipping and returned to pre-exercise and pre-shipping level in 30 min except fast gallop which returned to pre-exercise level in 1 hr.