Increased sensitivity to epinephrine of the cyclic AMP‐protein kinase system in adipose tissue of diabetic rats

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

doi:10.1016/0014-5793(78)80902-8

Cited by 14 publications

(9 citation statements)

References 11 publications

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“…'Lipolytic hypersensitivity' to epinephrine is reversible by insulin treatment [ 11. These findings are in accord with the recent observation that the cyclic AMP/protein kinase system of diabetic adipose tissue displays increased sensitivity to activation by epinephrine, but not to activation by adrenocorticotropin [2] these results point to an alteration of the catecholamine receptor/adenylate cyclase system in diabetic rat adipose tissue. To test this hypothesis basal and hormonestimulated adenylate cyclase activities were measured in fat-cell ghosts from normal and diabetic rats and compared with the lipolytic response and the activation of the cyclic-AMP-dependent protein kinase in 'intact' cells.…”

Section: Cyclic Amp Phosphodiesterase Activity Is Increased 55supporting

confidence: 81%

supporting

confidence: 81%

“…In this context also, the 1 0-fold increased sensitivity to adrenocorticotropin of adenylate cyclase in fat-cell ghosts from diabetic rats is in sharp contrast firstly to the relatively small apparent increase in lipolytic sensitivity towards adrenocorticotropin and the drastically reduced maximal lipolytic response in 'intact' diabetic fat cells (Fig. 2B), and secondly to the slightly decreased sensitivity towards adrenocorticotropin of lipolysis [ 11 and the unchanged sensitivity of the cyclic AMP-protein kinase system [2] in whole diabetic adipose tissue. In all of these respects, adrenocorticotropin-stimulated lipolysis differs considerably from epinephrine-stimulated lipolysis.…”

Section: Discussionmentioning

confidence: 92%

“…3) and whole diabetic adipose tissue [2]. Since hormone-sensitive triglyceride lipase is activated via a mechanism involving stimulation of adenylate cyclase and of the cyclic AMP/protein kinase system (for review see [ 191 ) one would expect this enzyme, and hence lipolysis, to 'respond' to lower concentrations of the hormone in the diabetic than in the normal fat-cell or tissue.…”

Section: Discussionmentioning

confidence: 99%

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

Zumstein¹,

Zapf²,

Waldvogel³

et al. 1980

Eur J Biochem

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1. Adenylate cyclase in fat-cell ghosts from streptozotocin-diabetic rats is 34% lower than in normal rats. Relative to the basal activity, maximal stimulation by epinephrine and isoproterenol is 10-fold in normal and 14-fold in diabetic fat cells, whereas maximal stimulation by fluoride is 7-fold in both states.2. The sensitivity of adenylate cyclase to epinephrine and isoproterenol is increased in fat-cell ghosts from diabetic rats : the concentrations of these catecholamines required for half-maximal activation of adenylate cyclase is three times lower in diabetic than in normal cells. In contrast, half-maximal stimulation by fluoride occurs at the same concentration in both states.3. Epinephrine-induced activation of cyclic-AMP-dependent protein kinase and of lipolysis correlate with the activation of adenylate cyclase. The epinephrine concentration required for halfmaximal activation of cyclic-AMP-dependent protein kinase and of lipolysis is three times lower in diabetic than in normal cells.in fat-cell homogenates and fat-cell ghosts from diabetic rats. Phosphodiesterase is, therefore, unlikely to be involved in the mechanism causing the 'hypersensitivity phenomenon'.5. The sensitivity of adenylate cyclase to adrenocorticotropin is increased 1 0-fold in fat-cell ghosts from diabetic rats. However, no correlation between adrenocorticotropin-stimulated adenylate cyclase activity and lipolysis is observed. Concentrations required to elicit the first measurable activation of adenylate cyclase stimulate glycerol production maximally. Stimulation of glycerol production starts at 1 00-fold lower concentrations than stimulation of adenylate cyclase.6. Insulin treatment of diabetic rats for 24 h reduces the response of adenylate cyclase to both epinephrine and adrenocorticotropin as compared with saline-treated diabetic animals.It is concluded that the increased sensitivity of adenylate cyclase to epinephrine in diabetic fat-cells is responsible for the enhanced lipolytic sensitivity to this hormone. Increased sensitivity of adenylate cyclase may be due to a change in the binding affinity of the hormone receptor or to altered properties of the coupling mechanism between the receptor and the catalytic subunit of adenylate cyclase. Cyclic AMP phosphodiesterase activity is increased 55Adipose tissue from streptozotocin-diabetic rats is 5 -10-times more sensitive to the lipolytic action of epinephrine, but not to that of adrenocorticotropin, glucagon and dibutyryl adenosine 3',5'-monophosphate than adipose tissue from normal rats [l] . 'Lipolytic hypersensitivity' to epinephrine is reversible by insulin treatment [ 11. These findings are in accord with the recent observation that the cyclic AMP/protein kinase system of diabetic adipose tissue displays increased sensitivity to activation by epinephrine, but not to activation by adrenocorticotropin [2]. Altogether Abbreoiution. Cyclic AMP, adenosine 3',5'-monophosphate. Enzymes. Adenylate cyclase (EC 4.6.1.1); cyclic AMP phosphodiesterase (EC 3.1.4.17); phosphocreatine ...

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Section: Cyclic Amp Phosphodiesterase Activity Is Increased 55supporting

confidence: 81%

supporting

confidence: 81%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Zumstein¹,

Zapf²,

Waldvogel³

et al. 1980

Eur J Biochem

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“…It is well known that diabetes is associated with an increase in plasma free fatty acid and the rate of basal lipolysis (5,(22)(23)(24). In the present study, basal FFA production was increased by diabetes (5.5 fold).…”

Section: Discussionsupporting

confidence: 62%

Basal Lipolysis in Epididymal Fat Cells from Streptozotocin-Induced Diabetic Rats

Tsujita

2006

J Nutr Sci Vitaminol

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SummaryThe level of free fatty acid (FFA) in plasma is increased by diabetes. The increase in plasma FFA levels accompanied the stimulation of basal lipolysis (i.e. lipolysis in the absence of lipolytic agents) in fat cells. Injection of streptozotocin with rats resulted in a significant increase in basal FFA production (5.5 fold) in fat cells. However, basal glycerol production in fat cells was increased only 1.5 fold by streptozotocin-induced diabetes, implying that FFA re-esterification in fat cells was decreased by streptozotocin-induced diabetes. The FFA re-esterification in fat cells was also decreased by 1 d of fasting. Although basal lipolysis was increased by streptozotocin-induced diabetes or 1-d fasting, neutral triacylglycerol lipase activity and the immunoreactive HSL protein content in fat cells from streptozotocin-induced diabetic rats or 1-d fasting rats were not significantly changed. Although ␤ -blockers inhibited lipolysis induced by norepinephrine at a concentration of 10 Ϫ 4 M , it failed to inhibit the basal lipolysis and FFA re-esterification in fat cells from streptozotocin-induced diabetic rats. Nor did insulin or H-89, another antilipolytic agent, affect basal lipolysis or FFA re-esterification in fat cells from streptozotocin-induced diabetic rats. These results indicate that basal FFA production may be induced by a decrease of re-esterification of FFA in diabetic rats and is not affected by antilipolytic agents such as insulin, ␤ -blockers or H-89.

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Phospholipid methyltransferase activity in diabetic rat fat cells: effect of isoproterenol and insulin

Chiappe

1992

Mol Cell Biochem

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The effects of isoproterenol and insulin on phospholipid methyltransferase (PLMT) activity were investigated in adipocytes from control and streptozotocin-diabetic rats. PLMT activity was assayed by measuring the rate of incorporation of 3H-methyl groups from S-adenosyl-L-[methyl-3H] methionine into phospholipids. Basal PLMT activity was higher in adipocytes from diabetic animals. Treatment of adipocytes with isoproterenol induced a concentration-dependent stimulation of PLMT activity. In control adipocytes, the maximal effect was obtained at 100 nM isoproterenol with 2.3 fold increase in PLMT activity and a half maximal effect at 25 nM. In adipocytes from diabetic rats, a lower dose of isoproterenol (10 nM), caused 1.2 fold increase with a half maximal effect at 4 nM. Addition of 100 nM insulin inhibited basal PLMT activity and the stimulatory effect of isoproterenol in both types of adipocytes. The beta-adrenergic blocking agent propranolol inhibited the stimulatory effect of isoproterenol on PLMT activity in control and diabetic adipocytes. Intracellular concentration of cAMP was higher in diabetic adipocytes but decreased to normal values after incubation in the presence of insulin.

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Increased sensitivity to epinephrine of the cyclic AMP‐protein kinase system in adipose tissue of diabetic rats

Cited by 14 publications

References 11 publications

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

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

Basal Lipolysis in Epididymal Fat Cells from Streptozotocin-Induced Diabetic Rats

Phospholipid methyltransferase activity in diabetic rat fat cells: effect of isoproterenol and insulin

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