Insulin receptor kinase activity in muscles and white adipose tissue during course of VMH obesity

Early after lesion of the ventromedial hypothalamus nuclei (VMH), insulin-induced glucose utilization is increased in white adipose tissue (WAT), whereas oxidative and glycolytic muscles are, respectively, normoresponsive or resistant to insulin. Five weeks later, all of the muscles are resistant, whereas WAT returns to normal responsiveness. The aim of this study was to characterize the insulin receptor kinase activity in WAT and muscles 1 and 6 wk after lesion. The number and affinity of insulin receptors were not modified in any of the tissues studied. Autophosphorylation and phosphorylation of an exogenous substrate were similar in oxidative and glycolytic muscles of VMH and control rats both 1 and 6 wk after the lesion. Insulin receptors from WAT of 1-wk VMH rats exhibited a 2.5-fold increase in insulin-stimulated autophosphorylation and phosphorylation. Six weeks after the lesion, both autophosphorylation and phosphorylation returned to normal values. This suggests that insulin receptor tyrosine kinase activity does not play a significant role in the insulin resistance of skeletal muscles but has a crucial role in mediating the variations of insulin action on WAT observed during the development of VMH obesity.

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Insulin-receptor kinase activity of adipose tissue from morbidly obese humans with and without NIDDM

Diabetes ◽

10.2337/diabetes.36.5.620 ◽

1987 ◽

Vol 36 (5) ◽

pp. 620-625 ◽

Cited By ~ 24

Author(s):

M. K. Sinha ◽

W. J. Pories ◽

E. G. Flickinger ◽

D. Meelheim ◽

J. F. Caro

Keyword(s):

Adipose Tissue ◽

Insulin Receptor ◽

Kinase Activity ◽

Morbidly Obese ◽

Receptor Kinase ◽

Insulin Receptor Kinase ◽

Insulin Receptor Kinase Activity

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Insulin receptor kinase is hyperresponsive in adipocytes of young obese Zucker rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1987.252.2.e273 ◽

1987 ◽

Vol 252 (2) ◽

pp. E273-E278 ◽

Cited By ~ 1

Author(s):

A. Debant ◽

M. Guerre-Millo ◽

Y. Le Marchand-Brustel ◽

P. Freychet ◽

M. Lavau ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Receptor ◽

Insulin Action ◽

Kinase Activity ◽

Insulin Receptors ◽

Zucker Rats ◽

Receptor Kinase ◽

Insulin Receptor Tyrosine Kinase ◽

Obese Zucker Rats ◽

Insulin Receptor Kinase

Thirty-day-old obese Zucker rats have hyperresponsive adipose tissue, whereas their skeletal muscle normally responds to insulin in vitro. To further substantiate the role of insulin receptor tyrosine kinase in insulin action, we have studied the kinase activity of receptors obtained from adipocytes and skeletal muscle of these young obese Zucker rats. Insulin receptors, partially purified by wheat germ agglutinin agarose chromatography from plasma membranes of isolated adipocytes or from skeletal muscles, were studied in a cell-free system for auto-phosphorylation and for their ability to phosphorylate a synthetic glutamate-tyrosine copolymer. For an identical amount of receptors, the insulin stimulatory action on its beta-subunit receptor phosphorylation was markedly augmented in preparations from hyperresponsive adipocytes of obese animals compared with lean rats. Basal phosphorylation of adipocyte insulin receptors was nearly identical in lean and obese animals. Similarly the capacity of adipocyte insulin receptors to catalyze the phosphorylation of the synthetic substrate in response to insulin was increased. By contrast, the kinase activity of insulin receptors prepared from normally insulin-responsive skeletal muscle was similar in preparations of lean and obese rats. These results show that a state of hyperresponsiveness to insulin is correlated with a parallel increase of insulin receptor kinase activity suggesting an important role for this activity in insulin action.

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Insulin-Receptor Kinase Activity of Adipose Tissue From Morbidly Obese Humans With and Without NIDDM

Diabetes ◽

10.2337/diab.36.5.620 ◽

1987 ◽

Vol 36 (5) ◽

pp. 620-625 ◽

Cited By ~ 31

Author(s):

M. K. Sinha ◽

W. J. Pories ◽

E. G. Flickinger ◽

D. Meelheim ◽

J. F. Caro

Keyword(s):

Adipose Tissue ◽

Insulin Receptor ◽

Kinase Activity ◽

Morbidly Obese ◽

Receptor Kinase ◽

Insulin Receptor Kinase ◽

Insulin Receptor Kinase Activity

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Lipid-induced insulin resistance in cultured hepatoma cells is associated with a decreased insulin receptor tyrosine kinase activity.

Cell Regulation ◽

10.1091/mbc.2.1.65 ◽

1991 ◽

Vol 2 (1) ◽

pp. 65-72 ◽

Cited By ~ 12

Author(s):

P Hubert ◽

C Bruneau-Wack ◽

G Cremel ◽

Y Le Marchand-Brustel ◽

C Staedel

Keyword(s):

Insulin Resistance ◽

Insulin Receptor ◽

Kinase Activity ◽

Insulin Binding ◽

Hepatoma Cells ◽

Receptor Kinase ◽

Insulin Receptor Tyrosine Kinase ◽

Normal Medium ◽

Insulin Receptor Kinase ◽

Insulin Receptor Kinase Activity

We have shown previously that experimental modifications of the cellular lipid composition of an insulin-sensitive rat hepatoma cell line (Zajdela Hepatoma Culture, ZHC) affect both binding and biological actions of insulin. Discrepancies between insulin binding and actions implied a postbinding defect, responsible for the observed insulin resistance in lipid-treated cells. To elucidate the mechanism for this defect, we have studied insulin binding and insulin receptor kinase activity in partially purified receptor preparations from ZHC cells grown either in normal medium or in medium supplemented with linoleic acid or 25-hydroxycholesterol. Insulin binding to the lectin-purified insulin receptor showed only a small alteration in receptor affinity for the preparations from lipid-treated cells. Insulin-stimulated autophosphorylation of the beta-subunit of the insulin receptor, as well as insulin-induced phosphorylation of the artificial substrate poly(Glu,Tyr)4:1, was significantly decreased in the preparations from lipid-modified cells. Although differences in basal levels were observed, the magnitude of the insulin-stimulated kinase activity was significantly decreased in receptor preparations from lipid-treated cells. These findings indicate that experimental modification of the lipids of cultured hepatoma cells can produce in insulin receptor kinase activity changes that are proportional to the reduced insulin action observed in these cells.

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Hydrogen peroxide stimulates tyrosine phosphorylation of the insulin receptor and its tyrosine kinase activity in intact cells

Biochemical Journal ◽

10.1042/bj2500095 ◽

1988 ◽

Vol 250 (1) ◽

pp. 95-101 ◽

Cited By ~ 75

Author(s):

O Koshio ◽

Y Akanuma ◽

M Kasuga

Keyword(s):

Insulin Receptor ◽

Kinase Activity ◽

Intact Cell ◽

Insulin Receptors ◽

Beta Subunit ◽

Receptor Kinase ◽

Intact Cells ◽

Tyrosine Residues ◽

Insulin Receptor Kinase ◽

Insulin Receptor Kinase Activity

H-35 rat hepatoma cells were labelled with [32P]orthophosphate and their insulin receptors isolated on wheat germ agglutinin (WGA)-agarose and anti-(insulin receptor) serum. The incubation of these cells with 10 mM-H2O2 for 10 min increased the phosphorylation of both the serine and tyrosine residues of the beta subunit of the insulin receptor. Next, insulin receptors were purified on WGA-agarose from control and H2O2-treated H-35 cells and the purified fractions incubated with [gamma-32P]ATP and Mn2+. Phosphorylation of the beta subunit of insulin receptors obtained from H2O2-treated cells was 150% of that of control cells. The kinase activity of the WGA-purified receptor preparation obtained from H2O2-treated cells, as measured by phosphorylation of src-related synthetic peptide, was increased about 4-fold over control cells. These data suggest that in intact cell systems, H2O2 may increase the insulin receptor kinase activity by inducing phosphorylation of the beta subunit of insulin receptor.

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