Increased ribosomal biogenesis induces pancreatic beta cell failure in mice model of type 2 diabetes.
OBJECTIVE
To study the changes in gene expression by pancreatic beta cells under insulin resistance conditions.


METHODS
An exhaustive gene expression analysis was performed, using isolated pancreatic islets of obese diabetic model Lepr(-/-) mice. Overexpression of cyclin D2 was induced in cells from the pancreatic beta cell line, namely, INS-1.


RESULTS
Through a gene expression analysis using islets isolated from db/db mice, we found a significant increase in the expression of ribosome-related molecules. In addition, increased expression of cyclin D2 was found at certain protein levels. As INS-1 cells were induced to overexpress cyclin D2, we found an increase in the expression of ribosome-related molecules. Concurrently, an increase in the expression of endoplasmic reticulum stress (ER stress)-related molecules was also found.


CONCLUSIONS
In cases of pancreatic beta cell hyperplasia associated with insulin resistance, ribosomal biogenesis is increased, and ER stress is induced.
Asahara
Shun-ichiro
S
Department of Internal Medicine, Division of Diabetes, Metabolism, and Endocrinology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Matsuda
Tomokazu
T
Kido
Yoshiaki
Y
Kasuga
Masato
M
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D015870:Gene Expression; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*