Is glucagon involved in cold acclimatization?

Summary Cold acclimatization in rats at 5°C for 2 weeks caused a significant elevation of plasma glucagon concentration, accompanied by increased plasma FFA and glucose levels. Acute cold exposure at 5°C for 5 or 60 min did not affect these parameters in plasma.We are grateful to Drs.H. Ohhara andA. Kihara, Sapporo Medical College, for help in setting up glucagon radioimmunoassay.     

Is glucagon involved in cold acclimatization?

Cold acclimatization in rats at 5 degrees C for 2 weeks caused a significant elevation of plasma glucagon concentration, accompanied by increased plasma FFA and glucose levels. Acute cold exposure at 5 degrees C for 5 or 60 min did not affect these parameters in plasma.     

Direkte Hemmwirkung des Heparins auf die Insulinsekretion

Summary The injection of heparin into the A. pancreaticoduodenalis of anaesthetized dogs produces an immediate decrease of the IRI-concentration in the pancreatic and peripheral venous plasma. This decrease could not be correlated with any alteration of blood sugar or FFA. A direct inhibitory action of heparin on the pancreatic B-cell is suggested.     

The islet-acinar axis of the pancreas: Is there a role for glucagon or a glucagon-like peptide?

Intravenous glucagon inhibits exocrine pancreatic secretion in vivo, but exogenous glucagon does not affect exocrine secretion in vitro. Recent work, however, suggested that endogenous glucagon may be involved in the regulation of exocrine secretion even in vitro. We therefore investigated the effects of exogenous and endogenous glucagon on exocrine secretion by the isolated perfused rat pancreas in the presence of 1.8 mM glucose. Exogenous glucagon did not affect CCK-stimulated amylase output. 20 mM arginine stimulated glucagon release, but did not affect basal enzyme secretion. CCK-stimulated amylase output, however, was significantly inhibited in the presence of arginine. This inhibitory effect of arginine on exocrine pancreatic secretion could be blocked by glucagon antibodies, but not by nonspecific gammaglobulins. Thus exogenous glucagon failed to affect exocrine pancreatic secretion in vitro, but endogenously released glucagon or a glucagon-like peptide inhibited amylase release in the isolated perfused pancreas. We conclude that glucagon or a glucagon-like peptide may be a mediator in the islet-acinar axis.     

Stimulation of glucagon and inhibition of insulin secretion evoked from carotid baroreceptors

Summary The influence from carotid baroreceptors on portal immuno-reactive glucagon and insulin levels and on arterial plasma glucose concentration was studied in vagotomized cats by sectioning of the sinus nerves. Such a complete elimination of the afferent baroreceptor discharge caused a prompt and pronounced increase in the glucose and glucagon levels, whereas the insulin concentration significantly decreased. The role of vascular baroreceptors in the hyperglycemic response to hemorrhage is discussed.     

Stimulation of glucagon and inhibition of insulin secretion evoked from carotid baroreceptors.

The influence from carotid baroreceptors on portal immuno-reactive glucagon and insulin levels and on arterial plasma glucose concentration was studied in vagotomized cats by sectioning of the sinus nerves. Such a complete elimination of the afferent baroreceptor discharge caused a prompt and pronounced increase in the glucose and glucagon levels, whereas the insulin concentration significantly decreased. The role of vascular barorecptors in the hyperglycemic response to hemorrhage is discussed.     

Development and hormonal control of thioredoxin and the thioredoxin-reductase system in the rat liver during the perinatal period

The development and hormonal regulation of thioredoxin and of the thioredoxin-reductase system were investigated during the perinatal period in rat liver. An immunological procedure was developed in order to quantify thioredoxin in fetal and neonatal hepatocytes. Both immunoreactive thioredoxin and thioredoxin-reductase activity appeared on day 16.5 of pregnancy. The level of immunoreactive thioredoxin increased during the late fetal period, and its level was the same 24 h after birth. Moreover, its development was not subjected to hormonal regulation by corticosteroids and glucagon. In contrast, thioredoxin-reductase activity increased 3 times during the late fetal period and presented a marked increase 24 h after birth. In the absence of glucocorticoids there was no increase in the level of thioredoxin reductase, while administration of hydrocortisone acetate and glucagon to fetuses prematurely evoked its activity. This study suggests that if thioredoxin acts physiologically, this activity is related to the state of reduction of the molecule rather than to the total concentration in the liver.     

Development and hormonal control of thioredoxin and the thioredoxin-reductase system in the rat liver during the perinatal period

Summary The development and hormonal regulation of thioredoxin and of the thioredoxin-reductase system were investigated during the perinatal period in rat liver. An immunological procedure was developed in order to quantify thioredoxin in fetal and neonatal hepatocytes. Both immunoreactive thioredoxin and thioredoxin-reductase activity appeared on day 16.5 of pregnancy. The level of immunoreactive thioredoxin increased during the late fetal period, and its level was the same 24 h after birth. Moreover, its development was not subjected to hormonal regulation by corticosteroids and glucagon. In contrast, thioredoxin-reductase activity increased 3 times during the late fetal period and presented a marked increase 24 h after birth. In the absence of glucocorticoids there was no increase in the level of thioredoxin reductase, while administration of hydrocortisone acetate and glucagon to fetuses prematurely evoked its activity. This study suggests that if thioredoxin acts physiologically, this activity is related to the state of reduction of the molecule rather than to the total concentration in the liver.     

Effects of glucagon and insulin on the Paneth cells of the mouse duodenum.

The effect of glucagon and insulin on the paneth cells (PC) of the duodenum of the mouse was investigated using light microscopy. Both glucagon and insulin were able to increase significantly the number of the secretory granules of PC. This possibly means that these hormones are capable of inhibiting the secretion of PC.     

Long-chain fatty acid uptake by skeletal myocytes: a confocal laser scanning microscopy study

Studies of regulation of free fatty acid (FFA) utilization by skeletal muscles have focused on plasma FFA delivery and on intracellular factors affecting FFA metabolism. The present study was conducted to directly analyse the uptake process of fatty acids into single myocytes. Cells were isolated from the rat flexor digitorum brevis muscle. Confocal laser scanning microscopy was utilized to analyse the uptake of the fluorescent fatty acid derivative 12-NBD-stearate, which is not metabolized by muscle tissue. Uptake represented a saturable function of the unbound fatty acid concentration in the medium (K _m 366 ± 118 nM, V _max 2.1 ± 0.3 AU/s) and depended on the medium sodium concentration. Reduced buffer pH increased initial uptake rates, whereas lactate (10 mM) had no effect. Membrane hyper- and depolarization decreased uptake rates. This study demonstrates for the first time kinetic data from isolated myocytes with evidence for a carrier-mediated transport mechanism for long-chain fatty acids. Received 31 March 1998; accepted 8 May 1998     

Acute cold exposure increases the glucagon sensitivity of thermogenic metabolism in the rat

Summary Administration of glucagon to rats at 25°C had no effect upon their VO₂ while administration of noradrenaline or noradrenaline plus glucagon raised the VO₂-At 5°C, noradrenaline had no effect upon the cold-enhanced VO₂, while glucagon caused a rise of 13.7% implying increased glucagon sensitivity at 5°C. The glucagon-induced enhancement of VO₂ was abolished by concurrent administration of noradrenaline.     

Interaction of glucocorticosteroids with glucagon in the control of argininosuccinase activity in the fetal rat liver]

Exogenous glucagon, but not glucocorticosteroids cause a rise in argininosuccinase activity in the liver of 21.5 day old fetuses. When fetuses are deprived of glucocorticosteroids, glucagon is unable to promote the enzymic activity. This study indicates that glucocorticosteroids are required for the induction of the argininosuccinase activity by glucagon.     

Effect of glucagon on ethanol oxidation in isolated rat liver cells

Summary Addition of glucagon 5 min after ethanol was found to stimulate the rate of ethanol oxidation in hepatocytes isolated from starved rats. This stimulation is of the same order of magnitude as that mediated by asparagine. The glucagon effect is suppressed by antiproteolytic agents such as insulin or NH₄Cl. The stimulatingeffect of glucagon on ethanol oxidation is probably liked to enhanced proteolysis andan elevated glutamate level in the hepatocytes.Acknowledgments. this investigation was supported by grants from the Institut de la Santé de la Recherche Médicale, the Scientific Council of the Faculté de Médecine Paris-Ouest and the Ecole Pratique des Hautes Etudes (3rd section).     

Hemodynamic studies in acute venous stasis edema in rats

Summary An increase in venous pressure in the rat tail is known to result in acute edema. Acute venous stasis edema of the rat tail was induced by applying a force-controlled banding of standard tension (200 g) proximally for a period of 6–12 h. The hemodynamic changes of acute venous stasis edema were evaluated using non-invasive plethysmography, fluorescence angiography, computer thermography and invasive radioactive microsphere techniques. It is shown here that reduction of tail circulation to 40% of the control value is followed by prolonged vascular disorder characterized by genesis of reversible edema, increased total blood flow to the tail and decreased local cutaneous blood flow, without affecting the general hemodynamics. The cutaneous circulation (decreased blood flow) seems to be principally involved in the edemogenic response, whereas the deeper vessels (hyperemia) may or may not play a determinant role in acute experimental venous stasis edema in rats.Acknowledgment. The authors thank Mr G. Ponard for his technical assistance.     

Effects of adrenal demedullation combined with chemical sympathectomy on cold-induced responses of endocrine pancreas in rats

Adrenal demedullation combined with chemical sympathectomy with 6-hydroxydopamine (ACS) lowered plasma glucagon and insulin levels in rats. Acute cold exposure increased plasma glucagon in both ACS and control rats, while it increased plasma insulin only in ACS rats. ACS rats responded to cold with a smaller increase in plasma glycerol and a more pronounced elevation of plasma free fatty acids.     

Endocrine and exocrine pancreatic function after camostate-induced growth of the organ

It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment.In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased.     

Measurement of cyclic AMP in the islets of Langerhans of newborn rats. Effect of amino acids]

Radioimmunoassay of cyclic AMP (cAMP) in the islets of Langerhans from 48-64 h old Rats was performed after succinylation of the samples. cAMP was detected at 0.03 nM. The cAMP content of islets increases when L-arginine, L-lysine and L alanine are added together in the incubation medium at a concentration of 5-10 mM each. When phosphodiesterase is inhibited by theophylline the three amino acids considerably increase the cAMP content of islets. Thus an increase in cAMP content of the islets was observed with a concentration of amino acids which is efficient in stimulating the insulin and glucagon secretion.     

Hemodynamic studies in acute venous stasis edema in rats

An increase in venous pressure in the rat tail is known to result in acute edema. Acute venous stasis edema of the rat tail was induced by applying a force-controlled banding of standard tension (200 g) proximally for a period of 6-12 h. The hemodynamic changes of acute venous stasis edema were evaluated using non-invasive plethysmography, fluorescence angiography, computer thermography and invasive radioactive microsphere techniques. It is shown here that reduction of tail circulation to 40% of the control value is followed by prolonged vascular disorder characterized by genesis of reversible edema, increased total blood flow to the tail and decreased local cutaneous blood flow, without affecting the general hemodynamics. The cutaneous circulation (decreased blood flow) seems to be principally involved in the edemogenic response, whereas the deeper vessels (hyperemia) may or may not play a determinant role in acute experimental venous stasis edema in rats.     

Inhibitory effect of fasting on the glucagon-induced increase of liver phosphorylase A activity in rats

Summary The increase of liver phosphorylase A activity observed 1, 2 and 3 min after i.v. administration of 0.1 g kg^–1 glucagon to fed rats was found to be completely absent in 24 h fasted animals, although there is even an exaggerated liver cAMP response to glucagon after fasting.Acknowledgments. We would like to thank Mrs M. Fritzová and Mr F. Kovai for expert technical assistance.     

Acute cold exposure increases the glucagon sensitivity of thermogenic metabolism in the rat

Administration of glucagon to rats at 25 degrees C had no effect upon their VO2, while administration of noradrenaline or noradrenaline plus glucagon raised the VO2. At 5 degrees C, noradrenaline had no effect upon the cold-enhanced VO2, while glucagon caused a rise of 13.7%, implying increased glucagon sensitivity at 5 degrees C. The glucagon-induced enhancement of VO2 was abolished by concurrent administration of noradrenaline.