Differential requirement for p21ras activation in the metabolic signaling by insulin.
To evaluate the role of the "Ras pathway" in mediating metabolic signaling by insulin, we employed lovastatin to exhibit isoprenilation of Ras proteins in Rat-1 fibroblasts transfected with human insulin receptors (HIRc cells) and in differentiated 3T3-L1 adipocytes. Lovastatin blocked an ability of insulin to activate p21ras and mitogen-activated protein kinase. Lovastatin also significantly (p < 0.01) reduced insulin effects on thymidine incorporation and glucose incorporation into glycogen. Nevertheless, an effect of insulin on glucose uptake remained unaffected. It appears that in contrast to its mitogenic action and to its effect on glycogenesis, an effect of insulin on glucose uptake does not require p21ras activation.
Medical Research Service, Veterans Affairs Medical Center, Denver, Colorado 80220.
J E
JE
Reusch
P
P
Bhuripanyo
K
K
Carel
J W
JW
Leitner
P
P
Hsieh
D
D
DePaolo
B
B
Draznin
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000502:physiology*; D008148:Lovastatin / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects; D020663:ras Guanine Nucleotide Exchange Factors
D020662:Guanine Nucleotide Exchange Factors; D007328:Insulin; D011506:Proteins; D011994:Recombinant Proteins; D020663:ras Guanine Nucleotide Exchange Factors; D006003:Glycogen; D008148:Lovastatin; D011972:Receptor, Insulin; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D005947:Glucose