Showing papers in "Hormone and Metabolic Research in 1979"

Direct effect of corticosterone upon insulin secretion studied by three different techniques.

Abstract: The immediate effect of corticosterone upon insulin secretion rates estimated by three different techniques (perfusior of isolated rat pancreas and perifusion or incubation of isolated islets of Langerhans) was studied for one hour. Three corticosterone concentrations were used: 0.02, 0.2 or 20 mg/l. With 4.2 mmol/l glucose, corticosterone did not affect insulin secretion, whereas, with a stimulating glucose concentration (16.7 mmol/l), insulin secretion was inhibited by the three corticosterone concentrations tested during incubation experiments, and by only the two physiological ones (0.02 and 0.2 mg/l) during islets perifusion and pancreas perfusion experiments. Moreover the inhibitory effect appeared more rapid with perifused islets than perfused pancreas, where only the second insulin secretory phase was disturbed.

Effect of somatostatin on bile-induced acute hemorrhagic pancreatitis in the dog.

Abstract: In 21 female Beagle dogs an experimental pancreatitis was induced by injection of bile into the pancreatic duct system. Beside controls, dogs received 62.5 micrograms/h cyclic somatostatin (SRIF) a continuous i.v. infusion starting with a bolus of 250 micrograms 15 minutes before or 2 hours after bile injection. Following blood parameters were determined: lipase, amylase, blood count, minerals, glucose, insulin, gastrin, secretin and CCK. Two controls died within 24 hours, the others were sacrificed after 48 hours. All pancreata were examined morephologically. The controls developed all clinical signs of acute hemorrhagic pancreatitis, whereas all SRIF-treated dogs were in much better general condition. Lipase and amylase increased in all groups. In the controls insulin, gastrin and secretin remained unchanged and CCK rose slightly. SRIF-treatment diminished insulin, CCK and the test meal-induced increase of secretin. At autopsy the pancreata of the controls were nearly entirely apoplectic. The SRIF-treated dogs showed less damage of the pancreas and no severe hemorrhagic necrosis was noted. The beneficial effect of SRIF cannot only be due to an interaction with intestinal hormones. An additional direct protective effect on the exocrine parenchyma is proposed to exist.

Plasma lipids and high density lipoproteins during oral contraception with different combinations of ethinyl estradiol and levonorgestrel.

Abstract: This study evaluates the effects of 3 different combinations of ethinyl estradiol (EE) and gestagen levonorgestrel on the plasma concentrations of some lipids and lipoproteins. 75 healthy menstruating women from the Dept. of Obstetrics and Gynecology of Linkoping University were randomly assigned to 3 different treatment groups and were given either 1) EE 50 ug + levonorgestrel 250 ug (50/250); 2) EE 30 ug + levonorgestrel 150 ug (30/150); or 3) EE50 ug + levonorgestrel 125 ug (50/125). Fasting blood samples were collected before medication and on the 20th or 21st treatment day of cycles 1 3 and 6. No significant alterations of the mean blood pressure blood hemoglobin concentrations or erythrocyte sedimentation rate were observed in any of the groups. After 1-6 months of treatment with 50/125 triglyceride increased by 18-42%. In the group treated with 50/250 HDL-cholesterol and HDC phospholipids were reduced by 10%. No other parameter exhibited any consistent changes in any of the treatment groups. Elevated triglyceride concentrations and/or decreased HDL concentration increases cardiovascular risk. So as not to alter the HDL concentration it is recommended that a combined oral contraceptive should not contain more gestagen-androgen than corresponding to 125-150 ug. of levonorgestrel. A proportion of around 5:1 between levonorgestrel and EE may be needed to balance the changes of production and elimination of triglycerides.

In vitro effect of branched chain amino acids on the ribosomal cycle in muscles of fasted rats.

Abstract: 1) The effect of a single i.p injection of branched chain amino acids on ribosomal profiles of psoas muscles was studied in rats after a 48--96 hour fast. Experimental and control animals received glucose and insulin 1--2 hours before killing. 2) The ratio of polysomes to subunits and monomers decreased progressively during the fast. 3) The administration of the three branched chain amino acids together or leucine alone significantly increased the proportion of polysomes. 4) This effect was not observed in rats fed ad libitum. 5) It is suggested that the branched chain amino acids and specifically leucine may be required for the full protein anabolic response of muscles to insulin during a prolonged fast.

Effects of exercise stress on parotid gland secretion.

Abstract: Parotid secretion of alpha-amylase and potassium (K+) was determined in young adults following intense exercise. Exercise stress led to a significant elevation in alpha-amylase and K+ secretion, indicating an activation of adrenergic receptors supplying the parotid gland. Evidence of circadian variation or adaptation over days was not found.

Effect of Glucagon and Glomerulopressin on the Renal Function of the Dog

Abstract: Glucagon was infused through the porta or through the left renal artery in dogs. Another group of dogs were infused with glomerulopressin through the left renal artery. It was observed that glucagon when infused through the portal vein enhanced the glomerulopressin production and the glomerular filtration rate (GFR). When glucagon was infused intrarenally it did not alter GRF but it had a direct tubular action decreasing sodium reabsorption in the proximal tubule. Glomerulopressin infused intrarenally increased GRF and potassium excretion. The results suggest that the increase in GFR was due to increase in glomerulopressin activity. There are three reasons for this statement: a) GRF increased when glomerulopressin activity was high, but not when there was a low activity, 5) intrarenally infused glomerulopressin produced a very significant change in the GFR of the infused kidney, while the GRF of the contralateral kidney remained unchanged and c) intrarenally administered glucagon had no effect on GFR.

Testicular function in patients with spinal cord damage.

Abstract: Vaying degrees of testicular dysfunction are found in men with traumatic spinal cord damage. Eighteen paraplegic men have been studied and the gonadotropin response to luteinizing hormone-releasing hormone (LRH) measured. Basal serum testosterone estimations were made and in eight of the patients testicular testosterone reserve was assessed by the testosterone response to human chorionic gonadotropin (HCG). Testicular biopsies were performed in seven cases. In three of these patients, the testicular biopsies were abnormal. Five of the patients had elevated Follicle stimulating hormone levels and abnormalities of Luteinizing hormone kinetics were found in the same five patients. There was no significant difference between the plasma testosterone levels of the paraplegic patients when compared to the control group. In all the patients tested, there was an adequate testosterone reserve, and this included the three patients with the abnormal testicular biopsies. No relationship was found between the level of cord lesion and any of the hormonal parameters measured. This study confirms the primary nature of the seminiferous tubular damage which occurs in some patients with paraplegia.

Effects of pinealectomy and pineal incubation medium and sonicates on insulin release by isolated pancreatic islets in vitro.

Abstract: The present studies were designed to investigate the mechanism of previously-reported nocturnal hyperinsulinemia in the pinealectomized rat. Isolated islets were obtained from anesthetized control, sham-pinealectomized and pinealectomized rats, with 5 rats per surgical groups, during the early dark phase of the daily lightdark cycle. Batches of 3 islets each were incubated in various combinations of 2, 10 or 30 mM glucose with control buffer, medium in which cerebral cortex or pineal glands had previously been incubated for 2 hours, or sonicates of these same tissues. Insulin released into the culture medium was measured by radioimmunoassay. A significant hypersecretion of insulin was demonstrable in the islets from the pinealectomized animals. A stimulatory effect of both pineal medium and sonicates upon insulin release was similarly observed. Neither of these effects displayed an interaction with the concentration of glucose in the islet incubation medium and they, therefore, appear to be mediated by a mechanism which operates independently of stimulation by glucose. These results indicate that the rat pineal gland can exert direct effects upon insulin release from the islets, possibly through a humoral route. Further studies are in progress to characterize the nature and mode of action of the insulinotropic agent present in and released from the pineal gland.

Relaxin and collagen metabolism.

Abstract: The influence of the peptide hormone relaxin on collagen metabolism was studied in the symphysis pubis of the mouse. In the tissue the content of water and of acid soluble collagen in relation to total collagen is increased by hormonal treatment. Total collagen calculated in relation to the dry weight is decreased. Collagenase which was also detected in the symphyses of the controls is slightly enhanced. In serum collagen peptidase and collagen peptidase inhibitor as well as cyclic AMP exhibit distinctly increased levels. The effects can be suppressed by administration of relaxin-specific antisera. The data make clear that in the symphysis relaxin activates the collagenolytic system.

Glucose, insulin and somatostatin infusion for the determination of insulin resistance in liver cirrhosis.

Abstract: Twelve patients with liver cirrhosis and ten normal subjects were studied. Using a constant intravneous infusion of glucose, insulin and somatostatin over 2 1/2 hours we determined the stteady state plasma glucose level (SSPG) in order to measure insulin resistance. The results demonstrated that the cirrhotic patients were insulin resistant compared to normals and that plasma glucagon does not account for the insulin resistance in these patients.

Growth hormone reserve capacity in Turner's syndrome.

Abstract: In 11 untreated and 6 oestrogen-treated Turner's syndrome patients, the changes in the serum growth hormone level were studied following the induction of hypoglycaemia with insulin. The growth hormone was measured with a radioimmune assay technique. The growth hormone peak value measured in healthy females was 54.32 +/- 17.17, in untreated Turner's syndrome was 14.90 +/- 3.71, and in oestrogen-treated Turner patients was 33.38 +/- 9.22 microU/ml (average +/- standard error). On the basis of the results, a role is attributed to the decreased growth hormone reserve in the low growth of Tuner's syndrome patients.

The determinants of insulin extraction in the isolated perfused rat liver.

Abstract: The effect of hepatic blood flow and portal insulin concentration on insulin extraction during one passage through the isolated perfused rat liver was studied. The percentage of insulin extracted was constant over the physiological range of blood flows (4 to 28 ml/min). The total amount of insulin extracted increased as the input concentration was raised from 48 to 4860 microU/ml with the highest level of extraction being approximately 700 microU of insulin per gram of liver per minute. When square wave input pulses of 243 to 4860 microU/ml were presented, about 5% of this insulin was retained and then released by the liver for periods up to 15 minutes after the cessation of the input. The possible roles of glucose and glucagon as regulators of insulin extraction were studied. Glucose (300 mg/dl), as compared with no glucose, led to a significant reduction of insulin extraction (22% vs. 38%, p less than 0.001). Glucagon had no effect on insulin extraction in the presence of constant levels of glucose. It is concluded, therefore, that glucose may increase circulating insulin levels not only by its well known stimulation of insulin secretion by the pancreas, but also by inhibiting insulin extraction by the liver.

Comparison of several insulin-like effects of growth hormone.

Abstract: Three different insulin-like effects of growth hormone were studied in segments of adipose tissue obtained from hypophysectomized rats. The onset of each response was preceded by a characteristic lag period: antilipolysis was seen only after a 10--15 minute exposure to growth hormone; stimulation of glucose oxidation was significant 20 minutes after exposure to growth hormone and increased leucine oxidation was seen only after 30 minutes. Each of the responses was measurable without a detectable delay when the tissues were exposed to hormone during a prior incubation period. Accelerated leucine oxidation was detected when 0.01 microgram/ml growth hormone was present in the incubation medium; the other responses required a minimum of 0.1 microgram/ml. Inhibitors of protein synthesis of concentrations which decreased the incorporation of 14C leucine into protein by 99% had no effect on either the antilipolytic action of growth hormone or the stimulatory action on glucose oxidation, but abolished the acceleration of leucine oxidation. In contrast to findings in diaphragm muscle, theophylline was without effect on any of the insulin-like actions of growth hormone in adipose tissue, even though it decreased the basal rate of glucose and leucine oxidation.

Postnatal maturation patterns of serum corticosterone and growth hormone in rats: effect of chronic thyroxine administration.

Abstract: The effects of chronic neonatal hyperthyroidism in rats on the ontogenic pattern of serum corticosterone and growth hormone (GH) were studied Thyroxine (T4) treated and saline injected rat pups were sacrificed under basal and stress conditions In comparison to saline control animals, daily T4 administration (04 micrograms/gram body weight) produced a sustained elevation in basal corticosterone levels by day 12 and a significant elevation of serum corticosterone in response to stress by day 4 The serum GH levels in non-stressed animals were moderately decreased in response to T4 administration as compared to saline injected animals with a greater reduction in GH measured in samples obtained from stressed animals The results indicate that chronic T4 administration influences the developmental pattern of serum corticosterone and GH under both non-stress and stress conditions

Decrease in serum receptor-reactive somatomedin in diabetes.

Abstract: Somatomedin in rat serum has been measured by a sensitive radioreceptor assay using 125I-labelled human somatomedin and human placental membrane. In rats made diabetic with strepotzotocin, receptor-reactive somatomedin levels were decrease by up to 75%. The decrease followed the time course of increasing serum glucose and occurred to the same extent in rats aged between 4 and 40 weeks. Endogenous serum receptor-reactive somatomedin appeared exclusively in high molecular weight fractions on gel chromatography. In diabetes the decreased somatomedin was due to a fall in this high molecular weight activity, but was not accompanied by a fall in somatomedin binding protein. These results suggest a role for insulin in maintaining serum somatomedin levels.

Plasma catecholamine and parathyroid hormone responses in cattle during treadmill exercise at simulated high altitude.

Abstract: When steers were exposed to treadmill exercise at a simulated altitude of 3500 m, plasma concentrations of epinephrine and norepinephrine as well as of parathyroid hormone increased within minutes. Heart rate, erythrocyte number and plasma lactic acid level rose at the same time, whereas plasma free fatty acids showed a later increase. It is concluded, that the elevated parathyroid hormone levels were probably caused by sympathetic stimulation.

Propranolol inhibits the in vitro conversion of thyroxine into triiodothyronine by isolated rat liver parenchymal cells.

Abstract: A model for the in vitro study of the conversion of thyroxine into triiodothyronine using isolated rat liver parenchymal cells is described. Isolated liver cells (mean protein content 18 mg/ml) convert approximately 0.8% of 1.3 microM exogenously added T4 into T3 during thirty minutes incubation. Carbimazole (50 microM) has no effect on the conversion process, whereas propylthiouracil (50 microM) inhibits the conversion. The beta-adrenoceptor blocking agent propranolol lowers the conversion ratio when added in concentrations of 580 and 1160 microM, but has no inhibitory effect when 290 microM is added.

Serum T4, T3 and reverse T3 during treatment with propranolol in hyperthyroidism, L-T4 treated myxedema and in normal man.

Abstract: Serum concentrations of T4, T3 and reverse T3 were studied in two hyperthyroid groups (n = 13 and 11), in a group of normals (n = 9) and in a group of L-T4 substituted patients (n = 7) with severe pretreatment hypothyroidism. Serum T4 did not change except in one of the hyperthyroid groups change to in which a slight decrease was found. In all groups a significant fall in serum T3 and a significant rise in serum reverse T3 were found. An expected increase in serum TSH in the normal and in the L-T4 substituted groups could not be demonstrated.

Production of a specific antiserum by synthetic C-terminal fragment of glucagon.

Abstract: Seven rabbits were immunized with a synthetic C-terminal glucagon fragment [15--29] conjugated with bovine serum albumin by means of glutaraldehyde. Antisera for glucagon were produced in all the animals after six injections of the conjugate. One of them revealed a higher titer antiserum (G42), which did not cross react with gut glucagon-like immunoreactive material, secretin, insulin, gastric inhibitory polypeptide or vasoactive intestinal peptide. From the results of inhibition of 125 I-glucagon in binding with the antiserum by various glucagon-related fragments the immunogenic determinant of the antiserum was proved to be in the C-terminal residue of the glucagon molecule, although peptide [17--29] or [21--29] reacted weakly with the antiserum. The plasma glucagon levels measured by antiserum G 42 during an arginine test in five normal subjects were superposed on those obtained by other antiserum (G21), specific for pancreatic glucagon. Furthermore, a comparable standard curve for glucagon was obtained using antiserum G42, when a labelled p-hydroxyphenylacetylated glucagon fragment [15--29] was employed as a tracer. The present study clearly demonstrated that the C-terminal glucagon fragment could yield a specific antiserum for pancreatic glucagon, supporting the proposal that the C-terminal fragment of glucagon is responsible for such specific antisera. Furthermore, it is concluded that immunoassay for glucagon could be performed using the labelled glucagon fragment as a tracer.

Uptake and metabolism of exogenous and endogenous thyroxine in the brain of young rats.

Abstract: The uptake of labelled exogenous thyroxine by the brain was determined in 10- and 30-day-old rats. It was three times higher and thyroxine was more deiodinated on day 10 than on day 30. On the other hand, the endogenous hormonal iodine content was estimated in both the brain and the isolated cortical neurones in the young rats of the same ages equilibrated with 125I. On day 10, brain and neurones contained five times more thyroid hormones than on day 30. These results are discussed in the context of the relations previously discovered between development of thyroid function and brain maturation.

The use of perfused rat intestine to characterise the glucagon-like immunoreactivity released into serosal secretions following stimulation by glucose.

Abstract: Isolated perfused intestine of rat was used to demonstrate the glucose-stimulated release of glucagon-like immunoreactivity (GLI) into serosal secretions. The released GLI was characterised using immunoaffinity chromatography on columns of immobilised antibodies specific for the N (residues 1 to 18) and for the C (residues 19-29) terminal portions of glucagon followed by gel-filtration. The immunoreactivity was present in a variety of molecular species. These include a large GLI which has a molecular weight about 12000 and binds to antibodies specific for the N-terminal portion of glucagon and two polypeptide fractions with molecular weight closer to that of glucagon. While one fraction of the small GLI boun both to antibodies specific for the C-terminal and N-terminal portions of glucagon the other bound only to the former antibodies. The relevance of these findings to the origins of circulating GLI and the possible precursor relationship between large and other forms of GLI is discussed.

Effect of pentobarbital and urethane on the release of hypothalamic somatostatin and pituitary growth hormone.

Abstract: Hypothalamic somatostatin release was investigated in the rat to elucidate the mechanism of anesthetic action on growth hormone (GH) release from the pituitary. Intraperitoneal injection of sodium pentobarbital (5 mg/100 gm B.W.) significantly elevated serum GH levels and increased hypothalamic somatostatin concentration from basal values of 0.98 +/- 0.01 to 1.21 +/- 0.06 ng/mg wet wt. In contrast, urethane (150 mg/100 gm B.W., IP) administration lowered serum GH levels and hypothalamic somatostatin concentration (0.64 +/- 0.04 ng/mg wet wt.). However, the mean concentration of pancreatic somatostatin showed no change in either case. In rats receiving passive immunization with 0.5 ml rabbit antiserum to somatostatin (SRIF-AS), serum GH levels were significantly increased (67.5 +/- 12.3 ng/ml) and did not differ from those in the group treated with normal rabbit serum (NRS) plus pentobarbital (101.3 +/- 18.5 ng/ml). However, serum GH levels in rats injected with SRIF-AS plus pentobarbital were increased to higher values than in rats given SRIF-AS alone. When urethane was administered to rats after passive immunization with SRIF-AS, urethane-induced suppression of serum GH levels was markedly inhibited (5.5 +/- 2.0 vs. 33.5 +/- 7.5 ng/ml). These results suggest a possibility that the changes in serum GH levels observed with pentobarbital or urethane administration may be induced at least in one part by somatostatin released from the hypothalamus.