scholarly journals Time-dependence of biological activity induced by covalent insulin-receptor complexes in rat adipocytes

1985 ◽  
Vol 232 (1) ◽  
pp. 49-53 ◽  
Author(s):  
A Schüttler ◽  
C Diaconescu ◽  
D J Saunders ◽  
D Brandenburg
Keyword(s):  
Insulin Receptor ◽  
Inhibitory Effect ◽  
Receptor Complex ◽  
Half Time ◽  
Simple Method ◽  
Receptor Complexes ◽  
Maximal Stimulation ◽  
Monocomponent Insulin ◽  
Specific Receptors ◽  
Stimulation Of

Lipogenesis in isolated adipocyte preparations is stimulated when photosensitive insulin derivatives are attached covalently to specific receptors. This response was compared quantitatively with that to reversibly associated insulin, and it was shown that both covalent and reversible insulin-receptor complexes behave very similarly. The extent of stimulation of lipogenesis was studied as a function of time. Cells were incubated in buffer for various times before addition to vials containing 0 (basal) or 10 ng of monocomponent insulin/ml (maximal) and [U-3H]glucose. After 60 min, the toluene-soluble [3H]lipids were measured. The maximal stimulation induced by reversibly bound insulin was virtually constant over a period of 4 h. In contrast, adipocytes to which N alpha B2-(2-nitro-4-azidophenylacetyl)-des-PheB1-insulin had been covalently attached at the start of the experiment showed a loss of stimulation with time when incubated at 37 degrees C. This loss was decreased in the presence of lysosomotropic agents such as chloroquine at concentrations (approx. 200 microM) that had very little or no effect on the basal and maximal lipogenesis rates. A simple method was used to transform the measured rate of loss of stimulation into a rate of loss of effective units. A half-time of 80 min was calculated for the effective covalent insulin-receptor units in adipocytes at 37 degrees C at pH 7.4. This is very close to values reported by others for the internalization of covalent complexes in these cells, suggesting that this may be the causative event for the deactivation of the insulin-receptor unit. The inhibitory effect of chloroquine on the deactivation may indicate that the insulin-receptor complex can function even after internalization.

scholarly journals EXPERIMENTS ON THE RELATION OF THE INHIBITORY TO THE ACCELERATOR NERVES OF THE HEART

1897 ◽  
Vol 2 (2) ◽  
pp. 151-179 ◽  
Author(s):  
Reid Hunt
Keyword(s):  
Mode Of Action ◽  
Inhibitory Effect ◽  
Relative Strength ◽  
The Other ◽  
Maximal Stimulation ◽  
The One ◽  
Considerable Period ◽  
Minimal Stimulation ◽  
Ventricular Beat ◽  
Stimulation Of

The experiments described in Part IV of this paper show that in whatever manner the problem of the relation of the vagus to the accelerators is approached, whether the accelerators are stimulated during a stimulation of the vagus, or the vagus during a stimulation of the accelerators, or both are stimulated simultaneously, either for a short or for a longer period, the result is the same, viz., the effect upon the rate of the heart is determined entirely by the relative strength of the stimuli applied to the two nerves. If the stimuli are of approximately the same strength, as judged by the effect of stimulating the nerves separately, the rate of the heart is but slightly affected; if the stimulus applied to the vagus is the stronger, the heart is slowed; if it is weaker, the heart is accelerated. In all cases the result of stimulating the two nerves simultaneously is approximately the algebraic sum of the results of stimulating them separately; sometimes the inhibitory effect slightly predominates, but not more frequently than does the accelerator effect. Moreover, the two nerves may be stimulated simultaneously for a considerable period of time without either completely overcoming the effect of the other. Thus as far as their effect upon the rate of the ventricular beat is concerned, the vagus and accelerator nerves seem to be purely antagonistic; the statement that a minimal stimulation of the one can completely overcome a maximal stimulation of the other is undoubtedly incorrect, and the hypotheses as to the mode of action of these nerves upon the heart, based upon this statement, lose their chief support.

IGF-II receptors and IGF-II-stimulated glucose transport in human fat cells

1990 ◽  
Vol 258 (3) ◽  
pp. E534-E542 ◽  
Author(s):  
M. K. Sinha ◽  
C. Buchanan ◽  
C. Raineri-Maldonado ◽  
P. Khazanie ◽  
S. Atkinson ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Glucose Transport ◽  
Insulin Binding ◽  
Human Adipocytes ◽  
Maximal Stimulation ◽  
Factor Ii ◽  
Igf I ◽  
Displacement Experiments ◽  
Receptor Antibodies ◽  
Stimulation Of

Insulin-like growth factor II (IGF-II) receptors have been described in rat but not in human adipocytes. In both species, IGF-II has been reported to stimulate glucose transport by interacting with the insulin receptor. In this study, we have unequivocally demonstrated the presence of IGF-II receptors in human adipocytes. 125I-labeled IGF-II specifically binds to intact adipocytes, membranes, and lectin-purified detergent solubilized extracts. Through the use of 0.5 mM disuccinimidyl suberate, 125I-IGF-II is cross-linked to a 260-kDa protein that is identified as the IGF-II receptor by displacement experiments with unlabeled IGF-II, IGF-I, and insulin and either by immunoprecipitation or by Western blot analysis with mannose 6-phosphate receptor antibodies. The concentrations of IGF-II required for half-maximal and maximal stimulation of glucose transport in human adipocytes are 35 and 100 times more than that of insulin. The possibility of IGF-II stimulating glucose transport by interacting predominantly with the insulin receptor is suggested by the following: 1) the concentration of IGF-II that inhibits half of insulin binding is only 20 times more than that of insulin; 2) the lack of an additive effect of IGF-II and insulin for maximal stimulation of glucose transport; 3) the ability of monoclonal insulin receptor antibodies to decrease glucose transport stimulated by submaximal concentrations of both IGF-II and insulin; and 4) the ability of IGF-II to stimulate insulin receptor autophosphorylation albeit at a reduced potency when compared with insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

ASSESSMENT OF A TEST OF ADRENOCORTICAL FUNCTION USING β1–25 CORTICOTROPHIN

1969 ◽  
Vol 44 (4) ◽  
pp. 513-516
Author(s):  
K. WHALEY ◽  
W. P. SOUTTER ◽  
W. C. DICK ◽  
G. NUKI ◽  
W. W. DOWNIE
Keyword(s):  
Adrenal Cortex ◽  
Corticosteroid Therapy ◽  
Adrenocortical Function ◽  
Normal Range ◽  
Simple Method ◽  
Maximal Stimulation ◽  
Synthetic Polypeptides ◽  
Range Of Values ◽  
Stimulation Of

SUMMARY In ten patients with a variety of rheumatic disorders the changes in plasma corticosteroid (11-OHCS) levels have been studied after adrenocortical stimulation by a continuous 5 hr. infusion of Synacthen (Ciba) or by a single i.v. injection of 200 i.u. (320 μg.) Pentacosactride (Sandoz). Comparable increases were obtained using both synthetic polypeptides. It is suggested that administration of Pentacosactride intravenously is a simple method of obtaining prolonged maximal stimulation of the adrenal cortex. A normal range of values of plasma 11-OHCS, obtained from 28 subjects, is given, and it is shown that the results are reproducible. The results of tests in six subjects with secondary adrenal atrophy due to long-term corticosteroid therapy indicate that the test can discriminate between normal and subnormal adrenocortical function.

Interactions between effects of W-7, insulin, and hypoxia on glucose transport in skeletal muscle

1994 ◽  
Vol 267 (4) ◽  
pp. R888-R894 ◽  
Author(s):  
J. H. Youn ◽  
E. A. Gulve ◽  
E. J. Henriksen ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Inhibitory Effect ◽  
Insulin Stimulation ◽  
Calmodulin Antagonist ◽  
Insulin Levels ◽  
Maximal Stimulation ◽  
Fivefold Increase ◽  
Stimulation Of

The calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) stimulates glucose transport in skeletal muscle, apparently by raising cytosolic Ca2+ (P. Palade. J. Biol. Chem. 262: 6142-6148, 1987; J.H. Youn, E.A. Gulve, and J.O. Holloszy. Am. J. Physiol. 260 (Cell Physiol. 29): C555-C561, 1991). This study was performed to describe the interactions between the effects of W-7 and those of hypoxia and of insulin on glucose transport. The effect on 3-O-methylglucose (3-MG) transport of 50 microM W-7 was additive to the effect of a maximal insulin stimulus (2,000 microU/ml) but not to the effect of maximal (60 min) hypoxic stimulus, suggesting that W-7 stimulates glucose transport via the same pathway as hypoxia, independent of the pathway activated by insulin. The effect of 50 microM W-7 was additive to that of a submaximal (20 min) hypoxia stimulus, indicating that W-7 does not interfere with the stimulation of glucose transport by hypoxia. In contrast, 50 microM W-7 had an inhibitory effect on stimulation of 3-MG transport by submaximally effective insulin levels, causing a fivefold increase in the concentration of insulin needed to produce a half-maximal stimulation of 3-MG transport, from approximately 70 to approximately 350 microU/ml (P < 0.05). Thus these data demonstrate that W-7 selectively inhibits insulin stimulation of glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Receptors for bradykinin in rabbit aortae

1977 ◽  
Vol 55 (4) ◽  
pp. 855-867 ◽  
Author(s):  
D. Regoli ◽  
J. Barabé ◽  
W. K. Park
Keyword(s):  
Dose Response ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Mass Action ◽  
Response Curves ◽  
Terminal Fragment ◽  
Mass Action Law ◽  
New Type ◽  
Specific Receptors ◽  
Stimulation Of

Rabbit aorta strips respond to bradykinin (BK) and to the C-terminal fragment of BK, the octapeptide 1-8 BK (Octa) with sustained contractions which are presumably due to the stimulation of specific receptors, because they remain unchanged in presence of phentolamine, methysergide, mepyramine, 8-Leu-ATII, and indomethacin. Experimental dose–response curves of BK and Octa are very similar to the theoretical curves predicted by the mass-action law and show the classical hyperbolic shape; ratios of doses producing 16% and 84% of maximum effects are 1:20 for Octa and 1:19 for BK. The relations of stimulus and effect are linear, suggesting that the extents of the contractions are proportional to the number of receptors occupied by the agonists.Structure–activity studies performed with fragments and analogues of BK and with analogues of Octa have shown that 8-Phe is essential for activation of the aortic receptor, and plays an important role for the affinity. The octapeptide 1-8 sequence is more favorable than the nonapeptide, because BK (pD2 = 6.40) is less potent than Octa (pD2 = 7.19) and 9-Ala BK is a partial agonist.Antagonists for both Octa and BK have been found by replacing 8-Phe with aliphatic residues (Ala, Nle, Leu, Leu-OMe) in the octapeptide. Affinities of 8-Leu-Octa (pA2 = 6.75) and 8-Leu-OMe-Octa (pA2 = 6.66) for the aortic receptors are fairly high and the antagonism appears to be of the competitive type because pA2 – pA10 is close to 0.95 for both compounds.The inhibitory effect of these two compounds are specific for Octa and BK. It is concluded that rabbit aortae contain a new type of receptor for BK, different from those found in the intestine and the uterus of several species.

PKC-independent inhibition of cardiac L-type Ca2+ channel current by phorbol esters

1996 ◽  
Vol 270 (2) ◽  
pp. H620-H627 ◽  
Author(s):  
T. Asai ◽  
L. M. Shuba ◽  
D. J. Pelzer ◽  
T. F. McDonald
Keyword(s):  
Protein Kinase C ◽  
Phorbol Esters ◽  
Ventricular Myocytes ◽  
Inhibitory Effect ◽  
Independent Action ◽  
Independent Manner ◽  
Channel Current ◽  
Kinase C ◽  
Channel Currents ◽  
Stimulation Of

Active and inactive phorbol esters were applied to guinea pig ventricular myocytes to study the responses of L-type Ca2+ (ICa,L) and L-type Na+ (INa,L) currents. Phorbol 12-myristate 13-acetate (PMA) (10-100 rM) never stimulated ICa,L or INa,L and frequently depressed them by 5-30% in a voltage-independent manner. However, the phorbol ester consistently activated delayed-rectifying K+ (IK) and Cl- currents. The inhibition of ICa,L occurred approximately 3 times faster than comonitored stimulation of IK, and ICa,L and INa,L were unaffected by two interventions that suppressed IK stimulation [pretreatment with 50 microM 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) and dialysis with pCa 11 versus standard pCa 9 solution]. Inactive phorbol esters 4 alpha-phorbol 12,13-didecanoate (alpha-PDD) and 4 alpha-phorbol had little effect on IK, but alpha-PDD had a PMA-like inhibitory effect on Ca2+ channel currents. We conclude that, unlike the stimulation of IK by PMA, inhibition of Ca2+ channel current by phorbol esters is a protein kinase C-independent action.

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