A1-adenosine receptor-mediated inhibition of adipocyte adenylate cyclase and lipolysis in Zucker rats

Vannucci, Susan J.; Klim, C. M.; Martin, Louis F.; LaNoue, Kathryn F.

doi:10.1152/ajpendo.1989.257.6.e871

Cited by 39 publications

(36 citation statements)

References 37 publications

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“…Therefore, changes in adenosine levels and/or stimulation of adenosine receptors may influence the function of insulin in both responsiveness and sensitivity. The present study supports this view from the findings that ADA at concentrations sufficient to convert endogenous adenosine to inosine (10,19) reduced the stimulation of insulin on leptin secretion from freshly isolated rat adipocytes (Ta b l e 1). Actually, insulin caused a concentrationdependent release of adenosine from rat white adipocytes ( F i g .…”

Section: Discussionsupporting

confidence: 84%

“…Adenosine has an ability to mimic insulin action in tissues, especially the adipose tissue, where the effects of insulin are m o d i fied by changes in adenosine levels, including the effects on glucose transport (7,8), glucose oxidation (9,10), lipolysis (10,11), and the activity of cAMP phosphodiesterase (17) or pyruvate dehydrogenase (18). Therefore, changes in adenosine levels and/or stimulation of adenosine receptors may influence the function of insulin in both responsiveness and sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Under physiological concentrations, adenosine increased the sensitivity of glucose transport (7,8) and glucose oxidation and/or metabolism (9,10) to the stimulation with insulin in adipocytes. Also, the action of adenosine in adipose tissue appears to be mainly through activation of adenosine A 1 receptors (10,11). The release of adenosine from adipose tissue has also been demonstrated (12,13).…”

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confidence: 97%

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Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats.

et al. 2000

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Leptin, the o b gene product that can decrease caloric intake and increase energy expenditure, is functionally released by insulin from adipose tissue. Adenosine is thought to be an important regulator of the action of insulin in adipose tissue. The present study investigated the role of adenosine in the release of leptin by insulin in isolated rat white adipocytes. Release of leptin, measured by radioimmunoassay, from insulin-stimulated samples was seen after 30 min. Adenosine deaminase, at concentrations sufficient to metabolize endogenous adenosine, decreased insulin-stimulated leptin release. Also, the insulin-stimulated leptin release was completely blocked by the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Mediation of endogenous adenosine in this action of insulin was further supported by the assay of adenosine released into the medium from adipocytes stimulated with insulin. In addition, activation of adenosine A 1 receptors by N 6 -c y c l o p e n t y l a d e n o s i n e ( C PA) induced an increase in leptin release in a concentration-dependent manner that could be blocked by antagonists, either DPCPX or 8-(p-s u l f o p h e n y l ) t h e ophylline (8-SPT). In the presence of U73312, a specific inhibitor of phospholipase C (PLC), CPA -s t i m u l a t e d leptin secretion from adipocytes was reduced in a concentration-dependent manner, but it was not affected by U73343, the negative control for U73312. Moreover, chelerythrine and GF 109203X diminished the CPAstimulated leptin secretion at concentrations suff i c i e n t to inhibit protein kinase C (PKC). These results suggest that, in isolated white adipocytes, the released adenosine acts as a helper and/or a positive regulator for insulin in the release of leptin via an activation of adenosine A 1 receptors that involves the PLC-PKC p a t h w a y. Diabetes 4 9 :2 0-24, 2000 T he o b gene, which encodes a 167-amino acid peptide named leptin in white adipocytes (1), has received increasing attention for its role in the regulation of food intake and whole-body energy balance in rodents and humans (2,3). It has been demonstrated that circulatory leptin levels in rats were modulated by exogenous insulin (4) and o b gene expression was induced by corticosteroids (5). Insulin also stimulated the mRNA levels of the o b gene in rat adipocytes (6). Thus, insulin appears to be one of the important regulators of o b gene expression and leptin secretion in adipose tissue.Adenosine is another endogenous regulator in adipose tissue. Under physiological concentrations, adenosine increased the sensitivity of glucose transport (7,8) and glucose oxidation and/or metabolism (9,10) to the stimulation with insulin in adipocytes. Also, the action of adenosine in adipose tissue appears to be mainly through activation of adenosine A 1 receptors (10,11). The release of adenosine from adipose tissue has also been demonstrated (12,13). However, the role of adenosine in mediating the effect of insulin on leptin release is still unknown. Thus, in th...

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

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Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats.

et al. 2000

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“…A decreased blood flow in SAT was also observed in obese humans (43)(44)(45) and may be due to various tissue parameters such as the size of adipocytes, differences in the organization and permeability of the connective web, and the density of microvessels surrounding the microdialysis probe (46). However, a higher basal lipolytic activity of adipocytes derived from ZF rats was also shown in cell culture experiments (47).…”

Section: Adenosine-a1 Receptor-mediated Antilipolysismentioning

confidence: 81%

Characterization of Adenosine-A1 Receptor–Mediated Antilipolysis in Rats by Tissue Microdialysis, 1H-Spectroscopy, and Glucose Clamp Studies

et al. 2004

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Increased supply of fatty acids to muscle and liver is causally involved in the insulin resistance syndrome. Using a tissue microdialysis technique in Wistar and Zucker fatty (ZF) rats, we determined tissue glycerol levels as a marker of lipolysis in gastrocnemius muscle (gMT), subcutaneous adipose (SAT), and visceral adipose tissue (VAT) as well as the reduction of plasma free fatty acids, glycerol, and triglycerides caused by the antilipolysis-specific adenosine-A1 receptor agonist (ARA). In Wistar and ZF rats, ARA significantly lowered dialysate glycerol levels in SAT, VAT, and gMT. Whereas in SAT and VAT the decrease in dialysate glycerol indicated adipocytic antilipolysis, this decrease in gMT was not caused by a direct effect of ARA on intramyocellular lipolysis, as demonstrated by the lack of inhibition of the protein kinase A activity ratio in gMT. In addition, no differences of the fed-starved-refed dynamics of intramyocellular triglyceride levels compared with untreated controls were measured by in vivo 1 Hspectroscopy, excluding any adenylate cyclase-independent antilipolysis in muscle. Treatment with ARA resulted in pronounced reductions of plasma free fatty acids, glycerol, and triglycerides. Furthermore, in ZF rats, ARA treatment caused an immediate improvement of peripheral insulin sensitivity measured by the euglycemic-hyperinsulinemic glucose clamp technique.

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“…3B also shows that the ability of CL316,243 to stimulate G i -GTP exchange in adipocyte membranes was equivalent to that obtained with the A 1 -adenosine receptor agonist N 6 -cyclopentyladenosine (1.56 Ϯ 0.07; n ϭ 4; p Ͻ 0.001). N 6 -Cyclopentyladenosine served as a positive control because the A 1 -adenosine receptor is expressed in both primary adipocytes (43,44) and differentiated 3T3-F442A adipocytes (45) and couples to all three G␣ i species (46,47).…”

Section: Resultsmentioning

confidence: 99%

The β3-Adrenergic Receptor Activates Mitogen-activated Protein Kinase in Adipocytes through a Gi-dependent Mechanism

Soeder¹,

Snedden²,

Cao³

et al. 1999

Journal of Biological Chemistry

168

159

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32 P]GTP into G␣ s (1.57 ؎ 0.12; n ‫؍‬ 3) and G␣ i (1.68 ؎ 0.13; n ‫؍‬ 4) in adipocyte plasma membranes, directly demonstrating that ␤ 3 AR stimulation results in G i -GTP exchange. The ␤ 3 AR-stimulated increase in 8-azido-[ 32 P]GTP labeling of G␣ i was equivalent to that obtained with the A 1 -adenosine receptor agonist N 6 -cyclopentyladenosine (1.56 ؎ 0.07; n ‫؍‬ 4), whereas inclusion of unlabeled GTP (100 M) eliminated all binding. Stimulation of the ␤ 3 AR in 3T3-F442A adipocytes led to a 2-3-fold activation of mitogen-activated protein (MAP) kinase, as measured by extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation. Pretreatment of cells with pertussis toxin (PTX) eliminated MAP kinase activation by ␤ 3 AR, demonstrating that this response required receptor coupling to G i . Expression of the human ␤ 3 AR in HEK-293 cells reconstituted the PTX-sensitive stimulation of MAP kinase, demonstrating that this phenomenon is not exclusive to adipocytes or to the rodent ␤ 3 AR. ERK1/2 activation by the ␤ 3 AR was insensitive to the cAMP-dependent protein kinase inhibitor H-89 but was abolished by genistein and AG1478. These data indicate that constitutive ␤ 3 AR coupling to G i proteins serves both to restrain G s -mediated activation of adenylyl cyclase and to initiate additional signal transduction pathways, including the ERK1/2 MAP kinase cascade.Long before the discovery of the ␤ 3 AR and its recognition as a unique, adipocyte-specific receptor controlling lipolysis and thermogenesis, Rodbell and colleagues (1) made the observation that there was an unusual, biphasic stimulation of cAMP production in adipocytes in response to the ␤-adrenergic receptor agonist isoproterenol. Depending upon the concentration of GTP in the assay, isoproterenol could either stimulate or inhibit adenylyl cyclase activity in adipocyte plasma membranes. Murayama and Ui (2) showed that this inhibitory phase could be relieved by pretreatment of adipocytes with pertussis toxin (PTX).1 This curious observation lay fallow until studied later in greater detail by Bégin-Heick (3-5). However, it was not until the cloning and characterization of the ␤ 3 AR gene and the development of selective ␤ 3 AR agonists (6, 7) that it was postulated that this novel adipocyte-specific ␤AR may be responsible for the biphasic adenylyl cyclase response in adipocytes (8). We have previously noted that despite the relatively high level of expression of the ␤ 3 AR in adipocytes, the efficiency of coupling of the ␤ 3 AR to stimulation of adenylyl cyclase is low (9). However, there has been no clear biochemical demonstration of physical coupling of the ␤ 3 AR to G i , other than comparative functional experiments in the presence or absence of PTX (10), nor has there been any indication of what additional second messenger pathway may be activated as a consequence of this putative coupling of ␤ 3 AR to G i .Recently, many G protein-coupled receptors have been shown to mediate cellular growth or differentiation responses through the activation ...

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A1-adenosine receptor-mediated inhibition of adipocyte adenylate cyclase and lipolysis in Zucker rats

Cited by 39 publications

References 37 publications

Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats.

Role of adenosine in insulin-stimulated release of leptin from isolated white adipocytes of Wistar rats.

Characterization of Adenosine-A1 Receptor–Mediated Antilipolysis in Rats by Tissue Microdialysis, 1H-Spectroscopy, and Glucose Clamp Studies

The β3-Adrenergic Receptor Activates Mitogen-activated Protein Kinase in Adipocytes through a Gi-dependent Mechanism

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