scholarly journals Decreased tyrosine kinase activity of insulin receptor isolated from rat adipocytes rendered insulin-resistant by catecholamine treatment in vitro

1986 ◽  
Vol 234 (1) ◽  
pp. 59-66 ◽  
Author(s):  
H Häring ◽  
D Kirsch ◽  
B Obermaier ◽  
B Ermel ◽  
F Machicao
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Kinase Activity ◽  
Insulin Binding ◽  
Receptor Kinase ◽  
Rat Adipocytes ◽  
Insulin Resistant ◽  
32P Incorporation ◽  
Insulin Responsiveness

Catecholamine treatment of isolated rat adipocytes decreases insulin binding and inhibits insulin stimulation of the glucose-transport system. There is increasing evidence that the insulin signal is transmitted after insulin is bound to the receptor via a tyrosine kinase, which is an intrinsic part of the receptor. To find whether the receptor kinase is modified by catecholamines, we solubilized and partially purified the insulin receptor of isoprenaline-treated adipocytes and studied the effect of insulin on its kinase activity. (1) Insulin increased the tyrosine autophosphorylation of the insulin receptor kinase from catecholamine-treated cells only 4-fold, compared with a 12-fold stimulation in control cells. (2) The rate of insulin-stimulated 32P incorporation into the receptor of isoprenaline-treated cells at non-saturating [32P]ATP concentrations (5 muM) was decreased to 5-8% of the values for receptor from control cells. (3) 125I-insulin binding to the partially purified receptor from catecholamine-treated cells was also markedly decreased. The insulin receptor from catecholamine treated cells bound 25-50% of the amount of insulin bound by the receptor from control cells at insulin concentrations of 10 pM-0.1 muM. Part of the impaired insulin-responsiveness of the receptor kinase of catecholamine-treated cells is therefore explained by impaired binding properties; however, an additional inhibition of the kinase activity of the insulin receptor from catecholamine-treated cells is evident. (4) This inhibition of kinase activity decreased when the concentration of [gamma-32P]ATP in the phosphorylation assay was increased. A Lineweaver-Burk analysis revealed that the Km for ATP of the receptor kinase from isoprenaline-treated cells was increased to approx. 100 muM, compared with approx. 25 muM for receptor of control cells. (5) We conclude from the data that catecholamine treatment of rat adipocytes modulates the kinase activity of the insulin receptor by increasing its Km for ATP and that this is part of the mechanism leading to insulin-resistance in these cells.

scholarly journals Tyrosine kinase activity of liver insulin receptor is inhibited in rats at term gestation

1989 ◽  
Vol 263 (1) ◽  
pp. 267-272 ◽  
Author(s):  
C Martínez ◽  
P Ruiz ◽  
A Andrés ◽  
J Satrústegui ◽  
J M Carrascosa
Keyword(s):  
Insulin Receptor ◽  
Kinase Activity ◽  
Insulin Signalling ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Late Gestation ◽  
Receptor Kinase ◽  
Pregnant Rats ◽  
Insulin Resistant ◽  
32P Incorporation

Late gestation is associated with insulin resistance in rats and humans. It has been reported that rats at term gestation show active hepatic gluconeogenesis and glycogenolysis, and diminished lipogenesis, despite normal or mildly elevated plasma insulin concentrations, indicating a state of resistance to the hormone action. Since autophosphorylation of the insulin receptor has been reported to play a key role in the hormone signal transduction, we have partially purified plasma-membrane liver insulin receptors from virgin and 22-day-pregnant rats and studied their binding and kinase activities. (1) Insulin binding to partially purified receptors does not appear to be influenced by gestation, as indicated by the observed KD and Bmax. values. (2) The rate of autophosphorylation and the maximal 32P incorporation into the receptor beta-subunit from pregnant rats at saturating concentrations of insulin are markedly decreased with respect to the corresponding values for virgin rats. (3) The diminished autophosphorylation rate was due to a decreased responsiveness of the kinase activity to the action of insulin. (4) Phosphorylation of the exogenous substrates casein and poly(Glu80Tyr20) by insulin-receptor kinase was also less when receptors from pregnant rats were used. These results show the existence of an impairment at the receptor kinase level of the insulin signalling mechanism that might be related to the insulin-resistant state characteristic of term gestation in rats.

scholarly journals ATP-dependent Desensitization of Insulin Binding and Tyrosine Kinase Activity of the Insulin Receptor Kinase

1998 ◽  
Vol 273 (34) ◽  
pp. 22007-22013 ◽  
Author(s):  
Jean-Olivier Contreres ◽  
Robert Faure ◽  
Gerardo Baquiran ◽  
John J. Bergeron ◽  
Barry I. Posner
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Kinase Activity ◽  
Insulin Binding ◽  
Receptor Kinase ◽  
Tyrosine Kinase Activity ◽  
Insulin Receptor Kinase

scholarly journals 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

1990 ◽  
Vol 266 (1) ◽  
pp. 107-113 ◽  
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.

Characterization of insulin receptor kinase activity and autophosphorylation in different skeletal muscle types

1991 ◽  
Vol 260 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
S. Azhar ◽  
J. C. Butte ◽  
R. F. Santos ◽  
C. E. Mondon ◽  
G. M. Reaven
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Kinase Activity ◽  
Insulin Binding ◽  
Tyrosine Kinase Activity ◽  
Fiber Composition ◽  
Muscle Types ◽  
Skeletal Muscle Types

We have examined insulin binding, autophosphorylation, and tyrosine kinase activity in detergent-solubilized and wheat germ agglutinin-purified insulin receptor preparations from four rat muscles of different fiber composition (i.e., tensor fascia latae, soleus, vastus intermedius, and plantaris). Insulin binding activity was similar in three of the four muscles but lower in tensor fascia latae. No significant differences were noted in the affinity of insulin for its receptor from various muscle types. Insulin receptor tyrosine kinase activity measured in the absence (basal) and presence of insulin (0.3-300 nM) was comparable in all muscle types (normalized to the amount of insulin bound). Insulin sensitivity, measured as the dose of insulin required for half-maximal activation of kinase activity, was also similar in all muscle types. Likewise, incubation of receptor preparations with [gamma-32P]ATP, Mn2+, and insulin (0.25-100 nM) resulted in a dose-dependent autophosphorylation of the beta-subunit (relative molecular weight approximately 95 kDa) with similar kinetics in all muscle types. In conclusion, these results show that the functional behavior of the insulin receptor autophosphorylation-kinase system (in vitro) is not changed by alterations in muscle fiber composition, indicating that differences in insulin sensitivity between different skeletal muscle types is probably not due to modulation of the insulin receptor phosphorylation system.

scholarly journals Effects of metformin on insulin receptor tyrosine kinase activity in rat adipocytes

Diabetologia ◽  
1986 ◽  
Vol 29 (11) ◽  
pp. 798-801 ◽  
Author(s):  
D. B. Jacobs ◽  
G. R. Hayes ◽  
J. A. Truglia ◽  
D. H. Lockwood
Keyword(s):  
Tyrosine Kinase ◽  
Insulin Receptor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Activity ◽  
Tyrosine Kinase Activity ◽  
Insulin Receptor Tyrosine Kinase ◽  
Rat Adipocytes
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