ANTAGONISM BETWEEN INSULIN AND SELECTIVE ADRENERGIC AGONISTS ON THE GLYCOGEN SYNTHETASE AND PHOSPHORYLASE SYSTEMS OF THE ISOLATED RAT DIAPHRAGM

1975 ◽  
Vol 78 (2) ◽  
pp. 392-400
Author(s):  
Arne T. Hostmark ◽  
Ole Grønnerød ◽  
Robert S. Horn

ABSTRACT The antagonism between insulin and selective adrenergic stimulation on the converting systems for glycogen synthetase and phosphorylase has been investigated in the isolated rat diaphragm. Insulin significantly inhibited stimulation by terbutaline and noradrenaline of phosphorylase b to a conversion as well as stimulation of glycogen synthetase I to D conversion by these agents. The inhibition by insulin was stronger on the synthetase system than on the phosphorylase system. The insulin effect was not dependent upon the presence of glucose. In diaphragms from 24 h fasted rats the response of the phosphorylase system to both agonists decreased. Inhibition by insulin of terbutaline stimulated phosphorylase conversion was maintained upon fasting while no effect of insulin against stimulation by noradrenaline could be obtained in diaphragms from fasted rats. The effects of fasting and insulin were not influenced by beta adrenergic antagonists (practolol and butoxamine). The results indicate a difference in sensitivity of the synthetase and phosphorylase systems to insulin and suggest that noradrenaline and terbutaline influence glycogen metabolism by differing mechanisms.

1991 ◽  
Vol 159 (1) ◽  
pp. 185-202 ◽  
Author(s):  
C. L. Milligan

A method is described for the isolation of calcium-tolerant myocytes from adult rainbow trout. Isolated myocytes remain viable for at least 4 h in suspension as indicated by (1) maintenance of ATP, phosphocreatine (PCr) and glycogen levels; (2) maintenance of the integrity of cell membranes, shown by low rates of leakage of lactate dehydrogenase (LDH) to the medium and exclusion of Trypan Blue; (3) the ability to metabolize substrates; and (4) sensitivity to adrenergic agonists. CO2 production from both glucose and lactate was sensitive to adrenergic stimulation, with the following order of potency: isoproterenol greater than noradrenaline much greater than adrenaline greater than phenylephrine, which indicates the presence of beta 1-adrenoceptors. Myocytes isolated from trout acclimated to 20 degrees C in the summer were more sensitive to beta-adrenergic stimulation than myocytes isolated from trout acclimated to 9 degrees C in either summer or winter. In the absence of exogenous fuel, there was a net reduction in myocyte glycogen content and glycogenolysis was further stimulated by 10(−7) mmol l-1 noradrenaline. However, in the presence of exogenous fuel (either 5 mmol l-1 lactate or 5 mmol l-1 glucose), glycogen was ‘spared’ and noradrenaline-stimulated glycogenolysis was apparently inhibited.


1960 ◽  
Vol 198 (5) ◽  
pp. 1075-1078 ◽  
Author(s):  
E. R. Berman ◽  
E. Wertheimer

A factor has been found in the serum of fasted rats which inhibits glucose uptake and glycogen synthesis in the isolated rat diaphragm. It does not affect CO2 production or O2 uptake. It is nondialyzable, stable in the cold and also stable when heated to 58°C for 1 hour. It was found in Cohn fraction IV-V. Its action did not resemble any of the known hormones, nor could it be identified as one of the inhibitory factors found in diabetic serum.


1959 ◽  
Vol 18 (4) ◽  
pp. 395-408 ◽  
Author(s):  
K. L. MANCHESTER ◽  
P. J. RANDLE ◽  
F. G. YOUNG

SUMMARY 1. The effect of hypophysectomy, or of adrenalectomy, and injection of pituitary growth hormone (GH) or of cortisol, on the uptake of glucose and the incorporation of glycine into protein by isolated rat diaphragm, and the effect of the addition of insulin in vitro on these processes, has been studied. 2. Both hypophysectomy and adrenalectomy raised the uptake of glucose by isolated diaphragm, while treatment of the intact or of the hypophysectomized rat with GH, or of the intact or of the adrenalectomized rat with cortisol, depressed it. Although hypophysectomy and adrenalectomy did not influence the additional glucose uptake induced by 200 mu./ml. of insulin in vitro, both these operations enhanced the effect of 0·1–1·0 mu./ml. of insulin on glucose uptake by diaphragm in vitro. Treatment of the rat with GH or cortisol diminished the rise in glucose uptake of diaphragm induced by 0·1–1·0 mu./ml. insulin. 3. Hypophysectomy depressed, and administration of GH to the intact or hypophysectomized rat raised, the incorporation of glycine into protein of the isolated diaphragm, but neither of these operations altered the magnitude of the stimulation of incorporation induced by 1·0 mu./ml. insulin. 4. Adrenalectomy raised, and administration of cortisol to the intact or adrenalectomized rat depressed, the incorporation of glycine into protein of the isolated diaphragm; adrenalectomy enhanced, the injection of cortisol diminished, the effect of 1·0 mu./ml. insulin on these processes. 5. The possibility that GH directs insulin towards the stimulation of protein synthesis, in part by restraining the action of insulin on carbohydrate metabolism, is discussed.


1985 ◽  
Vol 249 (2) ◽  
pp. G197-G202 ◽  
Author(s):  
G. M. Short ◽  
G. M. Reel ◽  
J. W. Doyle ◽  
M. M. Wolfe

The present studies were directed toward examining the effects of gastrin-releasing peptide (GRP) on acid secretion and on beta-adrenergic-stimulated gastrin and somatostatin release using the isolated vascularly perfused rat stomach. Including pentagastrin in perfusion buffer increased acid output from 2.2 +/- 0.4 mueq H+/h during control perfusion to 18.8 +/- 1.8 mueq H+/h (P less than 0.01). No significant changes in acid secretion were detected when either GRP or specific antibodies to GRP were included in perfusate in the absence or presence of pentagastrin. Inclusion of 10(-9) M isoproterenol in the perfusate did not change acid output with respect to control; however, gastrin and somatostatin release into the portal venous effluent was significantly enhanced. Peak gastrin and somatostatin concentrations observed at 15 min were 753 +/- 43% (P less than 0.001) and 345 +/- 43% (P less than 0.01), respectively, of basal levels. When antibodies to GRP were included in perfusate containing isoproterenol, gastrin and somatostatin release into the portal venous effluent was significantly inhibited. The results of these studies indicate that GRP does not affect basal or pentagastrin-stimulated gastric acid secretion in the isolated perfused rat stomach. However, under the conditions of these experiments, beta-adrenergic stimulation of gastrin and somatostatin release appears to be mediated, at least in part, through GRP.


1963 ◽  
Vol 44 (1) ◽  
pp. 90-100
Author(s):  
P. R. Bouman ◽  
W. Dermer

ABSTRACT The in vitro effects of adrenaline on glycogen metabolism and glucose uptake were studied in diaphragms of intact, adrenalectomized and adrenodemedullated rats decapitated under »Nembutal« anaesthesia. Adrenalectomy and pretreatment of adrenalectomized rats with cortisol caused an increase in the net loss of glycogen induced by adrenaline. When glycogen deposition in the absence of adrenaline was also taken into account, the overall magnitude of the glycogenolytic response appeared to be unchanged. The apparent qualitative change in response induced by these procedures was attributed to increased initial glycogen values. In diaphragms of adrenalectomized and adrenodemedullated rats the response to adrenaline was identical, the initial glycogen content being the same in these preparations. None of the experimental procedures affected the variable inhibition of glucose uptake by adrenaline. These results do not favour the existence of a »permissive« or synergistic action of adrenocortical steroids with regard to the effects of adrenaline on peripheral carbohydrate metabolism.


1960 ◽  
Vol XXXV (IV) ◽  
pp. 541-550 ◽  
Author(s):  
P. R. Bouman ◽  
W. Dermer

ABSTRACT Hemidiaphragms of intact and adrenalectomized rats which had been killed by decapitation, were incubated for 1 hour at 37° C under aerobic conditions. Glucose uptake and glycogen deposition were determined. Addition of adrenaline in vitro (1 μg/ml) caused a substantial decrease in glucose uptake in both types of diaphragms, this decrease being equivalent to a simultaneous inhibition of glycogen deposition. »Nembutal« anaesthesia prior to decapitation was found to alter the response to adrenaline. This change was most clearly observed in diaphragms of adrenalectomized rats. Here, adrenaline mainly affected glycogen metabolism by way of glycogen degradation, whereas the overall magnitude of the response was not materially changed. However, glucose uptake appeared to be only slightly decreased by adrenaline under these conditions. The change in response to adrenaline was attributed to the higher initial glycogen content observed in diaphragms of nembutalized rats. It was suggested that prevention of an acute release of endogenous adrenergic substances, occurring after decapitation of unanaesthetized donor rats, may be the actual cause of this phenomenon. Attention was drawn to the significance of the initial glycogen content as an important factor in carbohydrate metabolism of the isolated rat diaphragm.


FEBS Letters ◽  
1980 ◽  
Vol 120 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Mary C. Sugden ◽  
Ann F.C. Tordoff ◽  
Vera Ilic ◽  
Dermont H. Williamson

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