Adrenergic Receptors and Cyclic Amp in the Regulation of Human Adipose Tissue Lipolysis*

Burns, Thomas W.; Langley, Paul E.; Robison, G. Alan

doi:10.1111/j.1749-6632.1971.tb45242.x

Cited by 70 publications

(18 citation statements)

References 13 publications

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“…One study noted a decrease of ACTH-stimulated lipolysis in 1-yr-old rats compared to those 50 days old (26) while another report found that ACTH-stimulated lipolysis was proportional to cell-surface area in rats of unspecified age (29). In contrast to the rat, adult human fat has been found insensitive to ACTH as a lipolytic hormone (30 While the present studies define a range of agerelated effects on hormone-sensitive adenylate cyclase, one must be cautious in attempting to correlate age changes of enzyme activation with overall metabolic responses such as lipolysis. As already shown in a few studies, phosphodiesterase activity appears to increase with aging and/or enlarging cell size in the rat (20, 3 1).…”

Section: Discussionmentioning

confidence: 97%

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Cooper¹,

Gregerman²

1976

J. Clin. Invest.

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A B S T R A C T The possibility has been explored that decreases of adenylate cyclase may explain diminished hormone sensitivity of adipose tissue with aging. Isolated cells were prepared from epididymal fat pads of rats 1-, 2-, 6-, 12-, and 24-mo-old, fixed in OsO, and sized and counted with a Coulter apparatus. Adenylate cyclase was assayed in cell membranes (ghosts) using [ra-P] 6 and 24 mo per cell. Glucagon stimulated adenylate cyclase 4.5-fold relative to basal in the 1-mo-old rat, but its effect then rapidly decreased and was absent by 12 mo. The fourfold stimulation by ACTH noted in the 1-mo-old animals decreased gradually with age but was still twice basal at 24 mo. Since no significant change of cell size occurred after 6 mo, diminished hormone sensitivity with senescence cannot be related to cell size. Similar age-related patterns of hormonal activation were evoked by 5'-guanylyl-imidodiphosphate [GMP-P(NH)P], a nucleotide analogue which increased both basal-and hormone-activated enzyme at all ages studied. Dose-response curves to hormones, fluoride, and GMP-P(NH)P were not affected by age. High Mg++ (50 mM) in the presence of GMP-P-(NH) P stimulated adenylate cyclase to levels greater than with fluoride, but a similar loss of activity with aging was still observed. Loss of hormone receptors may partially explain the age-related decreases of glucagon and ACTH-sensitive adenylate cyclase, but decreased basal-, epinephrine-, fluoride-, and GMP-P-(NH)P-stimulated responses suggest loss of the catalytic component of the adenylate cyclase enzyme complex in the aging fat cell membranes. INTRODUCTIONIn the past, most studies of aging and hormones have dealt with effects of hormones on the processes of aging or, more often, with effects of aging on hormone secretion and metabolism (1). More recently, however, effects of aging on hormone responsiveness or sensitivity have come under investigation. A number of postmaturational changes of this type have now been identified. In view of the variety of mechanisms involved in the actions of hormones of different types, it is not surprising that a mixed picture has emerged (2). For the many hormones whose mechanism of action involves activation of adenylate cyclase, relatively little information on age relationships is as yet available. To extend our information in this area, and with the hope of being able eventually to relate the findings to physiologic events, we have undertaken studies of adenylate cyclases in a variety of animal and human tissues.

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Section: Discussionmentioning

confidence: 97%

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Cooper¹,

Gregerman²

1976

J. Clin. Invest.

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Section: Introductionmentioning

confidence: 99%

“…In human adipose tissue studied in vitro, however, the lipolytic activity of glucagon has been difficult to detect (7)(8)(9)(10), and in intact man the ketogenic activity of glucagon has never been conclusively established (11)(12)(13). Hence, the ability of glucagon to stimulate these two processes in man has been questioned (8,9). The assessment of the lipolytic and ketogenic activity of glucagon in man has been complicated by the inherent capability of glucagon to stimulate insulin secretion (14) and the fact that insulin inhibits both lipolysis and ketogenesis (2,(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Effects of Glucagon on Lipolysis and Ketogenesis in Normal and Diabetic Men

Liljenquist¹,

Bomboy²,

Lewis³

et al. 1974

J. Clin. Invest.

138

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A B S T R A C T The effect of glucagon (50 ng/kg/min) on arterial glycerol concentration and net splanchnic production of total ketones and glucose was studied after an overnight fast in four normal and five insulin-dependent diabetic men. Brachial artery and hepatic vein catheters were inserted and splanchnic blood flow determined using indocyanine green. The glucagon infusion resulted in a mean circulating plasma level of 4,420 pg/mI.In the normal subjects, the glucagon infusion resulted in stimulation of insulin secretion indicated by rising levels of immunoreactive insulin and C-peptide immunoreactivity. Arterial glycerol concentration (an index of lipolysis) declined markedly and net splanchnic total ketone production was virtually abolished. In contrast, the diabetic subjects secreted no insulin (no rise in C-peptide immunoreactivity) in response to glucagon. Arterial glycerol and net splanchnic total ketone production in these subjects rose significantly (P = < 0.05) when compared with the results in four diabetics who received a saline infusion after undergoing the same catheterization procedure.Net splanchnic glucose production rose markedly during glucagon stimulation in the normals and diabetics despite the marked rise in insulin in the normals. Thus, the same level of circulating insulin which markedly suppressed lipolysis and ketogenesis in the normals failed to inhibit the glucagon-mediated increase in net splanchnic glucose production. It is concluded (a) that glucagon at high concentration is capable of stimulating lipolysis and ketogenesis in insulin-deficient diabetic man; (b) that insulin, mole for mole, has more antilipolytic activity in man than glucagon has lipolytic activity; and (c) that glucagon, on a molar basis, has greater stimulatory activity than insulin has inhibitory activity on hepatic glucose release.

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“…Catecholamine-induced lipolysis from adipocytes isolated from white fat in man (Burns et al, 1971), dog (Berlan & Dang Tran, 1978) and hamster (Hittelman et al, 1973;Giudicelli et al, 1977) is mediated through a stimulatory f$-adrenoceptor and an inhibitory a-adrenoceptor. Studies indicate that at,-and a2-adrenoceptors exist in hamster (GarciaSainz et al, 1980;Pecquery & Giudicelli, 1980) and human (Fain & Garcia-Sainz, 1983) fat cells.…”

Section: Introductionmentioning

confidence: 99%

[³H]‐idazoxan binds with high affinity to two sites on hamster adipocytes: an α₂‐adrenoceptor and a non‐adrenoceptor site

MacKinnon¹,

Brown²,

Spedding³

et al. 1989

British J Pharmacology

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Adrenergic Receptors and Cyclic Amp in the Regulation of Human Adipose Tissue Lipolysis*

Cited by 70 publications

References 13 publications

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Effects of Glucagon on Lipolysis and Ketogenesis in Normal and Diabetic Men

[³H]‐idazoxan binds with high affinity to two sites on hamster adipocytes: an α₂‐adrenoceptor and a non‐adrenoceptor site

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Adrenergic Receptors and Cyclic Amp in the Regulation of Human Adipose Tissue Lipolysis*

Cited by 70 publications

References 13 publications

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.

Effects of Glucagon on Lipolysis and Ketogenesis in Normal and Diabetic Men

[3H]‐idazoxan binds with high affinity to two sites on hamster adipocytes: an α2‐adrenoceptor and a non‐adrenoceptor site

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[³H]‐idazoxan binds with high affinity to two sites on hamster adipocytes: an α₂‐adrenoceptor and a non‐adrenoceptor site