Effect of a high-fat-sucrose diet on in vivo insulin receptor kinase activation

1990 ◽  
Vol 259 (1) ◽  
pp. E111-E116 ◽  
Author(s):  
J. J. Boyd ◽  
I. Contreras ◽  
M. Kern ◽  
E. B. Tapscott ◽  
D. L. Downes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Kinase Activity ◽  
Insulin Binding ◽  
Receptor Kinase ◽  
High Fat ◽  
Glucose Injection ◽  
Insulin Receptor Kinase

Insulin-stimulated glucose uptake into muscle is depressed by high-fat-sucrose (HFS) feeding of rats. To investigate the mechanism of this insulin resistance, the in vivo activation of the insulin receptor kinase in liver and muscle of control and HFS-fed rats was determined. Rats were injected with glucose and insulin and killed 0, 5, 15, and 30 min after injection. Insulin binding was not changed in partially purified receptors from muscle of HFS rats. In control rats insulin receptor kinase activity was maximally stimulated threefold in liver at 5 min and fourfold in muscle at 15 min after insulin-glucose injection. The insulin-stimulated tyrosine kinase activity of receptors isolated from the liver of rats fed the HFS diet was decreased by 30% in comparison with the controls. In contrast, receptors isolated from muscle did not show any difference in basal or insulin-stimulated kinase activity between HFS-fed and control rats. Decreased in vivo activation of the insulin receptor kinase may be at least partially responsible for insulin resistance in liver. Because insulin binding and insulin stimulation of receptor kinase were normal in muscle of HFS-fed animals, it is concluded that the insulin resistance of glucose uptake into muscle is caused by a defect distal to the insulin receptor.

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

1991 ◽  
Vol 2 (1) ◽  
pp. 65-72 ◽  
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.

Insulin resistance in uremia: insulin receptor kinase activity in liver and muscle from chronic uremic rats

1988 ◽  
Vol 254 (4) ◽  
pp. E394-E401 ◽  
Author(s):  
F. Cecchin ◽  
O. Ittoop ◽  
M. K. Sinha ◽  
J. F. Caro
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Kinase Activity ◽  
Insulin Binding ◽  
Beta Subunit ◽  
Receptor Kinase ◽  
Ad Libitum ◽  
Insulin Receptor Kinase ◽  
Insulin Receptor Kinase Activity

We have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. 125I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the beta-subunit and insulin receptor kinase activity using Glu80, Tyr20 as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristic of the receptors, as determined by electrophoretic mobilities of affinity labeled alpha-subunit and the phosphorylated beta-subunit, were normal in uremia. 125I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus our data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase.

Alteration of insulin-receptor kinase activity by high-fat feeding

Diabetes ◽  
1988 ◽  
Vol 37 (10) ◽  
pp. 1397-1404 ◽  
Author(s):  
T. Watarai ◽  
M. Kobayashi ◽  
Y. Takata ◽  
T. Sasaoka ◽  
M. Iwasaki ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Kinase Activity ◽  
Receptor Kinase ◽  
High Fat ◽  
Insulin Receptor Kinase ◽  
Insulin Receptor Kinase Activity ◽  
Fat Feeding

Mechanisms by Which Insulin and Muscle Contraction Stimulate Glucose Transport

1997 ◽  
Vol 22 (6) ◽  
pp. 519-530 ◽  
Author(s):  
Ronald N. Cortright ◽  
G. Lynis Dohm
Keyword(s):  
Insulin Receptor ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Initial Step ◽  
Insulin Binding ◽  
Channel Blockers ◽  
Receptor Kinase ◽  
Increase Insulin Sensitivity ◽  
Key Words Insulin ◽  
Insulin Receptor Kinase

Insulin binding to its receptor activates a tyrosine kinase that initiates a cascade of signaling events, the initial step being the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). Subsequent IRS-1 association and activation of phosphatidylinositiol 3-kinase (PI 3-kinase) is believed to be involved in the events leading to the translocation of glucose transporters (GLUT4) to the plasma membrane resulting in uptake of glucose into the cell. Muscle contractions increase insulin sensitivity, but also stimulate muscle glucose uptake independent of insulin. The contraction signaling pathway is distinct from the insulin pathway because the effect of insulin and contractions on glucose uptake are additive, and contractions do not increase insulin receptor kinase or PI 3-kinase activity. In contrast, studies indicating that contractions cause the translocation of GLUT4 and that both contractions and insulin-stimulated glucose transport can be blocked by calcium channel blockers suggest that the two pathways may converge. However, the possibility that two distinct GLUT4 pools may be targeted, one by insulin the other by contractions, indicates that additional research is needed to better define the mechanisms by which glucose transport is stimulated in muscle. Key words: insulin signaling, exercise

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 Elevated protein tyrosine phosphatase activity and increased membrane viscosity are associated with impaired activation of the insulin receptor kinase in old rats

1994 ◽  
Vol 298 (2) ◽  
pp. 443-450 ◽  
Author(s):  
O Nadiv ◽  
M Shinitzky ◽  
H Manu ◽  
D Hecht ◽  
C T Roberts ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Receptor Kinase ◽  
Membrane Viscosity ◽  
Liver Membranes ◽  
Old Rats ◽  
Insulin Receptor Kinase

Insulin resistance is very common in the elderly, and may be associated with glucose intolerance or frank diabetes. In previous studies we demonstrated that insulin resistance in old Wistar rats is associated with decreased autophosphorylation and activation of the hepatic insulin receptor kinase (IRK) in vivo. We now show that this defect can be reproduced in vitro, where the extent of insulin-induced activation of IRK in liver membranes of old rats was decreased by approximately 50% compared with young controls. The defect could be largely abolished after solubilization of the membranes with Triton X-100. We also show that: (a) the viscosity of membranes from the old rats was significantly (P < 0.001, n = 4) higher (by 15%) compared with young controls; (b) incubation of plasma membranes from old animals with lecithin liposomes, which lowered their cholesterol levels, partially abolished the defect in IRK activation; and (c) Triton extracts of liver membranes prepared from old rats did not interfere with the activation of IRK derived from young controls. Additionally, non-membrane components did contribute to the development of this defect. We observed a significant (approximately 30%) (P < 0.001, n = 18) elevation of cytosolic protein tyrosine phosphatase (PTP) activity directed against the beta subunit of the insulin receptor in livers of old rats. No such elevation of PTP activity could be demonstrated with synthetic substrates. Our findings are consistent with a model in which increased membrane viscosity as well as enhancement of a cytosolic PTP activity both markedly inhibit the activation in vivo of the hepatic IRK in old animals.

Sign in / Sign up

Export Citation Format

Share Document