Increased Sensitivity to Lipolytic Hormones of Adenylate Cyclase in Fat Cells of Diabetic Rats

Zumstein, Peter; Zapf, J.; Waldvogel, M.; Froesch, E. R.

doi:10.1111/j.1432-1033.1980.tb04488.x

Cited by 29 publications

(18 citation statements)

References 32 publications

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“…Supporting this is the finding that in adipocytes of the hyperinsulinaemic ob/ob mice, the defect in catecholaminestimulated adenylate cyclase [44-471 is correlated with changes in membrane fluidity [48] and is linked to a decreased scnsitivity of the system to guanine nucleotides [47]. Conversely, it was shown that in adipocytes of the insulinopaenic streptozotocin diabetic rats, the adenylate cyclase activity is, like in our present study, about three-times more sensitive to catecholamine than in adipocyte from non-diabetic rats [33]. Although in the latter study the adenylate cyclase-sensitivity to guanine nucleotides was not investigated, these data strongly suggest that the hypoinsulinaemic state induced by fasting could be, at least in part, responsible for the increased adenylate cyclase sensitivity to guanine nucleotides reported here.…”

Section: Discussionsupporting

confidence: 53%

“…It seems, on the contrary, that, because BtzcAMP mimicks the effects of cyclic AMP [50], the mechanism of the lipolytic defect found in fasted adipocytes is located at a site(s) beyond cyclic AMP synthesis. If, as suggested above, insulin deficiency is responsible for the changes observed at the membranous level, it does not appear to play any role in the lipolytic dcfect induced by fasting, since in adipocytes from diabetic rats, the sensitivity of lipolysis and of cyclic-AMP-dependent protein kinase to catecholamines has been shown to be markedly increased [33]. A decrease in triacylglycerol lipase content does not appear to be a likely mechanism as well, since basal lipolytic activity was not changed by fasting.…”

Section: Discussionmentioning

confidence: 95%

“…A possible explanation for this increased ability of adipocyte membranes to bind [3H]dihydroalprenolo1 after prolonged fasting is the occurrence of a change in membrane fluidity resulting in a demasking of preexistent receptors which would be unaccessible to adrenergic ligands in the fed state. In fact, changes in membrane fluidity, which have been shown in many systems to affect adenylate cyclase activation by the catecholamine-(P-receptor)complex [31,32], have been put forward to explain the increased sensitivity to catecholamines of the fat-cell adenylate cyclase system during insulin deficiency [33], a situation which also occurs after prolonged fasting [34]. Another possible mechanism for the increased number of P-adrenergic receptors is an increased receptor synthesis which could be secondary to hormonal changes due to fasting.…”

Section: Discussionmentioning

confidence: 99%

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Alterations Induced by a Prolonged Fasting: Opposite Effects on the β‐Adrenergic Receptor‐Coupled Adenylate‐Cyclase System and on Lipolysis in Fat Cells from Rat

Giudicelli

Lacasa

Agli

1982

European Journal of Biochemistry

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1. The maximal number of j-adrenergic receptors in rat fat-cell membranes from 72-h-fasted rats is about two-times higher than in fed rats. However, the affinity of these receptors for j-agonists and antagonists and the ability of guanosine 5'-[P,y-imido]triphosphate (100 pM) to reduce the receptor binding affinity for P-agonists are unaltered by fasting.2. Basal and fluoride-stimulated activities of adenylate cyclase are similar in adipocyte membranes from 72-hfasted and fed animals. However, relative to the basal activity, maximal stimulation by (-)-isoproterenol is 33 f 5 % higher in fasted than in fed adipocytes. The sensitivity of adenylate cyclase to (-)-isoproterenol is also increased in fat-cell membranes from fasted animals, as the concentration of (-)-isoproterenol required for halfmaximal activation is three-times lower in fasted than in fed adipocytes.3. Basal adenylate cyclase activity is also about three-times more sensitive to stimulation by guanosine 5'-[P,y-imido]triphosphate in fasted than in fed adipocyte membranes. This increased sensitivity of adenylate cyclase to guanosine 5'-[P,y-imido]triphosphate in fasting is much more pronounced when adenylate cyclase activity is stimulated by isoproterenol.4. In contrast, although basal lipolysis is unaltered by fasting, lipolysis stimulated in vitro by isoproterenol, adrenocorticotropin or dibutyryladenosine 3',5'-monophosphate is severely depressed in fat cells from 72-hfasted rats. However, the concentration of (-)-isoproterenol and adrenocorticotropin required for half-maximal activation of lipolysis are similar in fasted and fed adipocytes.From this study, it is concluded that, contrary to the fasting-induced decreased lipolytic responsiveness which is paradoxically observed in adipocytes in vitro, the fasting-induced changes found in the adenylate cyclasecoupled-0-adrenergic receptor-system of rat adipocyte are most probably physiologically relevant as these changes contribute to promote cyclic AMP synthesis and, consequently, to stimulate lipolysis, as is observed in vivo during fasting.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Alterations Induced by a Prolonged Fasting: Opposite Effects on the β‐Adrenergic Receptor‐Coupled Adenylate‐Cyclase System and on Lipolysis in Fat Cells from Rat

Giudicelli

Lacasa

Agli

1982

European Journal of Biochemistry

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“…In each case where responsiveness to stimulatory agonists is increased, that to inhibitory agents decreases, and vice versa. Thus hypothyroidism is associated with decreased stimulatory and increased inhibitory input (the present paper; Correze et al, 1974;Malbon et al, 1978;Ohisalo & Stouffer, 1979;Goswami & Rosenberg, 1980;Malbon & Graziano, 1983;Chohan et al, 1984;Malbon et al, 1984Malbon et al, , 1985, starvation with increased stimulatory and decreased inhibitory input (the present paper; Zapf et al, 1977;Honnor & Saggerson, 1980;Dax et al, 1981;Chohan & Saggerson, 1982;Chohan et al, 1984), and diabetes with increased responsiveness to stimulatory agonists (Zumstein et al, 1980;Chatzipanteli & Saggerson, 1983) and decreased sensitivity to PIA (K. Chatzipanteli & E. D. Saggerson, unpublished work).…”

Section: Discussionmentioning

confidence: 63%

Sensitivity of adipocyte lipolysis to stimulatory and inhibitory agonists in hypothyroidism and starvation

Saggerson¹

1986

Biochemical Journal

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1. The responsiveness of lipolysis to the stimulatory agonists noradrenaline, corticotropin and glucagon and to the inhibitory agonists N6-phenylisopropyladenosine, prostaglandin E1 and nicotinic acid was investigated with rat white adipocytes incubated with a high concentration of adenosine deaminase (1 unit/ml). 2. The cells were obtained from fed or 48 h-starved euthyroid animals or from fed or starved animals rendered hypothyroid by 4 weeks of treatment with low-iodine diet and propylthiouracil. 3. Hypothyroidism increased sensitivity to and efficacy of all three inhibitory agonists in their opposition of noradrenaline-stimulated lipolysis. Starvation decreased sensitivity to all three inhibitory agonists when opposing basal lipolysis. 4. Hypothyroidism decreased sensitivity to noradrenaline, glucagon and corticotropin by 37-, 4-and 4-fold respectively and decreased the maximum response to these agonists by approx. 50%, 50% and 75% respectively. Starvation reversed decreases in maximum response to these agonists in hypothyroidism. 5. Starvation in the euthyroid state increased sensitivity to glucagon and noradrenaline, but did not alter sensitivity to corticotropin. 6. Cells from hypothyroid rats were relatively insensitive to Bordetella pertussis toxin, which substantially increased basal lipolysis in the euthyroid state. INTRODUCTIONLipolysis in adipose tissue can be stimulated by the catecholamines, corticotropin and glucagon. Conversely, other agonists, e.g. adenosine, E-series prostaglandins and nicotinic acid, act through specific receptors to inhibit lipolysis. The activity of hormone-sensitive lipase is dependent on protein phosphorylation, which is the resultant of the activities of cyclic AMP-dependent protein kinase and phosphoprotein phosphatase(s). In turn, the cellular content of cyclic AMP is dependent on the relative activities of adenylate cyclase and cyclic nucleotide phosphodiesterase. Receptors for the inhibitory agonists are coupled to adenylate cyclase by a guanine nucleotide-binding protein (N1) distinct from that (N.) which couples receptors for stimulatory agonists to the enzyme (Rodbell, 1980;Murayama & Ui, 1983;Olansky et al., 1983;Moreno et al., 1983;Bokoch et al., 1984;Codina et al., 1984). In hypothyroidism adenylate cyclase, the increase in cyclic AMP, and lipolysis all show diminished responsiveness to the stimulatory agonists (Goodman & Bray, 1966;Armstrong et al., 1974;Correze et al., 1974;Malbon et al., 1978;Ohisalo & Stouffer, 1979;Goswami & Rosenberg, 1980). Conversely, the inhibitory effect of adenosine mediated by the A1 (Van Calker et al., 1979) or Ri (Londos et al., 1980) adenosine receptor is increased in hypothyroidism (Ohisalo & Stouffer, 1979;Malbon & Graziano, 1983;Chohan et al., 1984;Malbon et al., 1985). This enhanced responsiveness is most easily measured in the presence of adenosine deaminase by using the non-metabolized analogue PIA and appears to reflect an increase in the abundance of Ni in the adipocyte plasma membrane (Malbon et al., 1985) without any in...

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“…4A) is probably due, besides to possible changes in the number of receptors per cell with age (no definite data exist on this), to modifications of the sensitivity of the (intra)cellular enzymes involved in lipolysis as, for example, adenyl cyclase [Hartman et al, 1971;Cooper and Gregerman, 1976;Giudicelli and Pecquery, 1978;Dax et al, 1981] and phosphodiesterase activity [Forn et al, 1970;Dax et al, 1981]. It should moreover be noted that in vivo the response of the adi pocytes to epinephrine may be modulated by the plasma insulin level [Zapf et al, 1975[Zapf et al, , 1977Zumstein et al, 1980] through an ef fect on adenylate cyclase, since there was an increase of insulin level between 6 and 24 months (p < 0.05) and a decrease (though not significant) between 24 and 32 months [Dehez-Delhaye, 1978 …”

Section: Discussionmentioning

confidence: 99%

Changes in Lipolytic Activity of Isolated Adipocytes from Rats throughout Life Span

A¹,

Caucheteux²,

Delhaye³

et al. 1985

Gerontology

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The lipolytic response of isolated adipocytes from 1 ½-, 6-, 24- and 32-month-old rats to various doses of epinephrine was studied. Both the basal and the maximal stimulated glycerol release were largest in the mature rats (6 months old) which had the largest adipocytes. Expressing glycerol release per unit cell surface area (which was drastically reduced with age) eliminated the difference between mature and senescent rats both in absence of epinephrine and at high doses of the hormone. However, at low epinephrine doses the adipocytes of the very young and the very old rats showed an enhanced response per unit surface area. A simple pharmacodynamic analysis based on the occupancy theory of drug-receptor interaction suggests that the sensitivity of rat adipocyte receptors is increased during senescence; this increase may be related to the decreased surface of old adipocytes. On the other hand, the decreased maximal lipolytic response during senescence may be due in part to a reduced number of receptors and to a reduced sensitivity of the cellular enzymatic system underlying lipolysis.

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Increased Sensitivity to Lipolytic Hormones of Adenylate Cyclase in Fat Cells of Diabetic Rats

Cited by 29 publications

References 32 publications

Alterations Induced by a Prolonged Fasting: Opposite Effects on the β‐Adrenergic Receptor‐Coupled Adenylate‐Cyclase System and on Lipolysis in Fat Cells from Rat

Alterations Induced by a Prolonged Fasting: Opposite Effects on the β‐Adrenergic Receptor‐Coupled Adenylate‐Cyclase System and on Lipolysis in Fat Cells from Rat

Sensitivity of adipocyte lipolysis to stimulatory and inhibitory agonists in hypothyroidism and starvation

Changes in Lipolytic Activity of Isolated Adipocytes from Rats throughout Life Span

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