TY - JOUR
T1 - Unprocessed insulin proreceptor in cultured fibroblasts from a patient with extreme insulin resistance
AU - Sasaoka, Toshiyasu
AU - Shigeta, Yukio
AU - Takata, Yasumitsu
AU - Ishibashi, Osamu
AU - Sugibayashi, Masaaki
AU - Hisatomi, Akitaka
AU - Kobayashi, Masashi
N1 - Funding Information:
From the Third Department of Medicine, Shiga University of Medical Science, Ohtsu. Shiga, Japan, and the Diabetes Center, Kokura City Hospital, Kitakyusyushi, Japan. Supported in part by the research grant for the Intractable Diseasefrom the Ministry of Health and Welfare and a grant-in-aid from the Ministry of Education, Science, and Culture, Japan. Address reprint requests to Masashi Kobayashi, MD. Third Department of Medicine. Shiga University of Medical Science, Ohtsu, Shiga 520-21. Japan. B 1989 by W.B. Saunders Company. 0026-0495/89/381 O-001I %03.00/O
PY - 1989/10
Y1 - 1989/10
N2 - Insulin receptors and IGF-I receptors in cultured fibroblasts were investigated in a patient with extreme insulin resistance due to unprocessed insulin receptors. Insulin binding to cultured fibroblast monolayers and partially purified insulin receptors was extremely decreased to 27% and 18% of control value, respectively. Affinity cross-linking study revealed that molecular weight of the insulin receptor was 210 kDa and that it could not be dissociated to alpha- and beta-subunit with dithiothreitol treatment. Because IGF-I binding to the fibroblasts from the patient was normal and alpha-subunit of IGF-I receptor was 135 KDa, the defect was specific to the insulin receptor. Autophosphorylation of the 210 kDa unprocessed insulin proreceptor was stimulated by insulin in a dose-dependent manner. In the fibroblasts from the patient, insulin-stimulated alpha-aminoisobutyric acid uptake was fivefold shifted to the right in the dose-response curve (ED50 20 ng/mL for the patient v 3.5 ng/mL for the control subjects), but the maximally stimulated uptake was normal. With 0.025% trypsin treatment, insulin binding and alpha-aminoisobutyric acid uptake were normalized. These results suggested that (1) abnormal processing of insulin proreceptor also occurred in the cultured fibroblasts, (2) the postreceptor steps of insulin action were totally intact, and (3) IGF-I receptors were normally processed in this patient.
AB - Insulin receptors and IGF-I receptors in cultured fibroblasts were investigated in a patient with extreme insulin resistance due to unprocessed insulin receptors. Insulin binding to cultured fibroblast monolayers and partially purified insulin receptors was extremely decreased to 27% and 18% of control value, respectively. Affinity cross-linking study revealed that molecular weight of the insulin receptor was 210 kDa and that it could not be dissociated to alpha- and beta-subunit with dithiothreitol treatment. Because IGF-I binding to the fibroblasts from the patient was normal and alpha-subunit of IGF-I receptor was 135 KDa, the defect was specific to the insulin receptor. Autophosphorylation of the 210 kDa unprocessed insulin proreceptor was stimulated by insulin in a dose-dependent manner. In the fibroblasts from the patient, insulin-stimulated alpha-aminoisobutyric acid uptake was fivefold shifted to the right in the dose-response curve (ED50 20 ng/mL for the patient v 3.5 ng/mL for the control subjects), but the maximally stimulated uptake was normal. With 0.025% trypsin treatment, insulin binding and alpha-aminoisobutyric acid uptake were normalized. These results suggested that (1) abnormal processing of insulin proreceptor also occurred in the cultured fibroblasts, (2) the postreceptor steps of insulin action were totally intact, and (3) IGF-I receptors were normally processed in this patient.
UR - http://www.scopus.com/inward/record.url?scp=0024341861&partnerID=8YFLogxK
U2 - 10.1016/0026-0495(89)90011-5
DO - 10.1016/0026-0495(89)90011-5
M3 - 学術論文
C2 - 2552266
AN - SCOPUS:0024341861
SN - 0026-0495
VL - 38
SP - 990
EP - 996
JO - Metabolism
JF - Metabolism
IS - 10
ER -
