Diabetes & Metabolism Journal

Original Articles

Mitogenic Effects and Signaling Pathway of Insulin-Like Growth Factor-I (IGF-I) in the Rat Beta Cell Line (INS-1).: In Kyung Jeong, Ja Young Kim, Hyung Joon Yoo, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim; Korean Diabetes J. 2004;28(6):478-489. Published online December 1, 2004

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Abstract PDF: BACKGROUND
Nutrients and growth factors are known to stimulate pancreatic beta cell mitogenesis. IGF-I acts as a survival factor by limiting apoptosis and stimulating proliferation in many cell types. However, the appropriate mitogenic signaling pathways have not been defined. The aim of this study is to elucidate the mitogenic effect and signaling pathways of IGF-I in the rat beta cell line (INS-I). METHODS: The studies were performed using the rat pancreatic beta cell line, INS-1. INS-1 cells were cultured in RPMI 1640 containing serum-free, 0.2% BSA and 11.1 mmol/L glucose media for 24 hours, and the cells were then treated with IGF-I and different concentrations of glucose or tyrosine phosphorylation inhibitors, or insulin. The cell proliferation was measured by the [3H]thymidine uptake and MTT assay. The cell cycle was analyzed by a flow cytometer by using propidium iodide staining. Western blot analyses were performed using antibodies against PY20 and phospho-MAPK. RESULTS: 1) MTT assay and the [3H]thymidine uptake showed that IGF-I stimulated the INS-1 cell proliferation in a dose dependent manner. Glucose was noted to independently increase the INS-1 cell proliferation. A combination of IGF-I and glucose has a synergistic effect on the proliferation of INS-I cells. Insulin did not influence on the mitogenic effect of IGF-I. 2) The S fraction of INS-1 cells treated with IGF-I was increased in a dose dependent manner. IGF-I stimulated the exit from G1 into the S phase of the cell cycle. 3) Investigation of the role of the PI3K and MAPK, by using of the inhibitors LY294002, wortmannin, and PD98059, demonstrated that the activation of MAPK, but not PI3K, required to stimulate the proliferation of INS-1 cells. 4) IGF-I stimulated the phosphorylation activation of pp60 and phospho-MAPK in the INS-1 cells. IGF-I induced the beta cell proliferation, and this was mediated via a signaling mechanism that was facilitated by MAPK. CONCLUSION: The proliferative effect of IGF-I on pancreatic beta cell seems to be mediated through MAPK signaling pathway.

The Effects of Uncoupling Protein 3 Overexpression on Glucose Metabolism in OLETF Rats in Vivo and Cultured Skeletal Muscle Cells in Vitro.: Jeong Hee Han, Hye Seon Park, Jung Min Koh, Ha Young Kim, Ho Kyung Kang, In Kyu Lee, Joong Yeol Park, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee; Korean Diabetes J. 2001;25(6):460-468. Published online December 1, 2001

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Abstract PDF: BACKGROUND
UCP3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. METHODS: An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus- UCP3 (UCP3 group) and others were injected with the adenovirus (control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C12 cells transfected with ether an adenovirus or the adenovirus-UCP3. RESULTS: The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. CONCLUSION: Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism.

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