Effect of insulin and adrenergic agonists on glucose transport of porcine adipocytes

Abstract The sensitivities of lipolysis and fatty acid synthesis to dibutyryl-cAMP (dbcAMP), epinephrine, ractopamine and clenbuterol were quantified in vitro using porcine adipocytes. Insulin-stimulated lipogenesis showed a biphasic response to dbcAMP, with increased rates at low concentrations and decreased (55%) rates at higher concentrations of dbcAMP. In the absence of insulin, lipogenesis was inhibited 78% by dbcAMP. In the presence of adenosine deaminase or theophylline, all three β-adrenergic agonists inhibited basal lipogenesis, but only epinephrine and ractopamine inhibited insulin-stimulated lipogenesis. The relationship between suppressed lipogenesis and enhanced lipolysis in response to dbcAMP and the β-agonists revealed that 1) basal lipogenesis was more sensitive to inhibition than was the stimulation of lipolysis, 2) sensitivity differences were magnified if adenosine deaminase was present and 3) insulin decreased adipocyte sensitivity to the inhibitory effects of dbcAMP and the β-adrenergic agonists. These results indicate that the relative sensitivities of lipogenesis and lipolysis to β-adrenergic stimulation can be modified by adenosine and insulin. Furthermore, adenosine and insulin antagonize β-adrenergic responses, in part, by cAMP-independent mechanisms.

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Decreased insulin binding to porcine adipocytes in vitro by beta-adrenergic agonists.

Journal of Animal Science ◽

10.2527/1990.6861603x ◽

1990 ◽

Vol 68 (6) ◽

pp. 1603 ◽

Cited By ~ 13

Author(s):

C Y Liu ◽

S E Mills

Keyword(s):

Insulin Binding ◽

Adrenergic Agonists ◽

Beta Adrenergic ◽

Beta Adrenergic Agonists ◽

Porcine Adipocytes

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Apparent lack of beta 3-adrenoceptors and of insulin regulation of glucose transport in brown adipose tissue of guinea pigs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1995.268.1.r98 ◽

1995 ◽

Vol 268 (1) ◽

pp. R98-R104 ◽

Cited By ~ 2

Author(s):

J. Himms-Hagen ◽

J. Triandafillou ◽

N. Begin-Heick ◽

M. Ghorbani ◽

A. L. Kates

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Acclimation ◽

Glucose Transport ◽

Guinea Pigs ◽

Adrenergic Agonists ◽

Specific Expression ◽

Brown Adipocytes ◽

Apparent Lack ◽

Brown Adipose

Norepinephrine-induced thermogenesis was substantial in adipocytes from brown adipose tissue (BAT) of cold-acclimated guinea pigs but absent in adipocytes from BAT of warm-acclimated guinea pigs. There was no thermogenic response to any beta 3-adrenergic agonist (CL-316,243, ZD-7114, BRL-28410, CGP-12177). The receptor was characterized as a beta 1-adrenoceptor. Adrenergic agonists stimulated adenylate cyclase in membranes from BAT of both warm- and cold-acclimated guinea pigs also via a beta 1-adrenoceptor; beta 3-adrenergic agonists had no effect. Glucose transport by brown adipocytes from warm-acclimated guinea pigs was not stimulated by either norepinephrine or insulin. Cold acclimation induced the appearance of stimulation of glucose transport by norepinephrine in association with the appearance of a large capacity for thermogenesis, but there was little improvement in response to insulin. GLUT4 was present in membranes from BAT of both warm- and cold-acclimated guinea pigs. Insulin is known to have an antilipolytic effect on both BAT and white adipose tissue of guinea pigs. Thus there is a selective lack of insulin-regulated glucose transport that is not improved by cold acclimation. Guinea pigs may have a mutated component of the translocation mechanism for GLUT4. beta 3-Adrenoceptors appear to be absent in brown adipocytes of adult guinea pigs, as in white adipocytes of guinea pigs, yet are known to be present in the gut. Tissue-specific expression of beta 3-adrenergic receptors in guinea pigs may differ from that in rats, in which receptors are expressed in the adipose tissues and gut.

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The inhibition of insulin action and glucose metabolism by porcine growth hormone in porcine adipocytes is not the result of any decrease in insulin binding or insulin receptor kinase activity

Biochemical Journal ◽

10.1042/bj2660107 ◽

1990 ◽

Vol 266 (1) ◽

pp. 107-113 ◽

Cited By ~ 51

Author(s):

K A Magri ◽

M Adamo ◽

D Leroith ◽

T D Etherton

Keyword(s):

Insulin Receptor ◽

Glucose Transport ◽

Kinase Activity ◽

Insulin Binding ◽

Transport Rate ◽

Receptor Kinase ◽

Insulin Responsiveness ◽

Porcine Adipocytes ◽

Insulin Receptor Kinase ◽

Insulin Receptor Kinase Activity

The present study was undertaken to determine the effects of porcine growth hormone (pGH) on glucose transport, to establish which lipogenic enzymes were affected by pGH, and to determine if changes in insulin binding or insulin receptor kinase activity contributed to the diminished insulin responsiveness of adipocytes from pigs treated with pGH. Pigs were treated with pGH daily (70 micrograms/kg body wt.) for 7 days. pGH treatment reduced the basal (non-insulin-stimulated) glucose transport rate by 62% and the insulin-stimulated transport rate by 47%. The decline in glucose transport rate was paralleled by a 64% decrease in fatty acid synthesis. The reduction in the lipogenic rate was associated with a marked decline in the activity of several lipogenic enzymes: glucose-6-phosphate dehydrogenase (50% decrease), 6-phosphogluconate dehydrogenase (11% decrease), malic enzyme (62% decrease) and fatty acid synthase (activity not detectable after pGH treatment). The pGH-dependent decline in insulin responsiveness was not associated with any change in the binding of insulin to intact adipocytes or to plasma membrane preparations. The insulin-stimulated tyrosine kinase activity of the wheat-germ agglutinin-purified receptors from pGH-treated adipocytes was not different from that in control adipocytes, except when high concentrations of insulin were employed. These findings establish that pGH elicits a number of metabolic effects in porcine adipocytes which collectively diminish the rate of lipid synthesis, and thereby contribute to the decrease in lipid deposition observed in pGH-treated pigs. Furthermore, the pGH-dependent impairment in insulin action appears to be mediated at some location distal to the receptor kinase step or in other signal pathway(s) which mediate the biological effects of insulin that are not dependent on activation of insulin receptor tyrosine kinase activity.

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Role of glucose in modulating Mg2+ homeostasis in liver cells from starved rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00488.2003 ◽

2005 ◽

Vol 288 (2) ◽

pp. G195-G206 ◽

Cited By ~ 10

Author(s):

Lisa M. Torres ◽

Jonathan Youngner ◽

Andrea Romani

Keyword(s):

Glucose Transport ◽

Liver Cells ◽

Experimental Models ◽

Adrenergic Agonists ◽

Sprague Dawley ◽

Hepatic Glucose ◽

Extracellular Glucose ◽

Overnight Fasting ◽

Glucose Output

α1- and β-Adrenoceptor stimulation elicits Mg2+ extrusion from liver cells in conjunction with hepatic glucose output (T. Fagan and A. Romani. Am J Physiol Gastrointest Liver Physiol 279: G943–G950, 2000.). To characterize the role of intrahepatic glucose on Mg2+ transport, male Sprague-Dawley rats were starved overnight before being anesthetized and used as organ donors. Perfused livers or collagenase-dispersed hepatocytes were stimulated by α1 (phenylephrine)- or β (isoproterenol)-adrenergic agonists. Mg2+ extrusion was assessed by atomic absorbance spectrophotometry. In both experimental models, the administration of pharmacological doses of adrenergic agonists did not elicit Mg2+ extrusion. The determination of cellular Mg2+ indicated an ∼9% decrease in total hepatic Mg2+ content in liver cells after overnight fasting, whereas the ATP level was unchanged. Hepatocytes from starved rats accumulated approximately four times more Mg2+ than liver cells from fed animals. This enlarged Mg2+ accumulation depended in part on extracellular glucose, since it was markedly reduced in the absence of extracellular glucose or in the presence of the glucose transport inhibitor phloretin. The residual Mg2+ accumulation observed in the absence of extracellular glucose was completely abolished by imipramine or removal of extracellular Na+. Taken together, these data indicate 1) that hepatic glucose mobilization is essential for Mg2+ extrusion by adrenergic agonist and 2) that starved hepatocytes accumulate Mg2+ via two distinct pathways, one of which is associated with glucose transport, whereas the second can be tentatively identified as an imipramine-inhibited Na+-dependent pathway.

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