Gene interactions and pathways from curated databases and text-mining
PloS one 2011, PMID: 21886784

Ablation of TSC2 enhances insulin secretion by increasing the number of mitochondria through activation of mTORC1.

Koyanagi, Maki; Asahara, Shun-ichiro; Matsuda, Tomokazu; Hashimoto, Naoko; Shigeyama, Yutaka; Shibutani, Yuki; Kanno, Ayumi; Fuchita, Megumi; Mikami, Tomoko; Hosooka, Tetsutya; Inoue, Hiroshi; Matsumoto, Michihiro; Koike, Masato; Uchiyama, Yasuo; Noda, Tetsuo; Seino, Susumu; Kasuga, Masato; Kido, Yoshiaki

OBJECTIVE

We previously found that chronic tuberous sclerosis protein 2 (TSC2) deletion induces activation of mammalian target of rapamycin Complex 1 (mTORC1) and leads to hypertrophy of pancreatic beta cells from pancreatic beta cell-specific TSC2 knockout (βTSC2(-/-)) mice. The present study examines the effects of TSC2 ablation on insulin secretion from pancreatic beta cells.

METHODS

Isolated islets from βTSC2(-/-) mice and TSC2 knockdown insulin 1 (INS-1) insulinoma cells treated with small interfering ribonucleic acid were used to investigate insulin secretion, ATP content and the expression of mitochondrial genes.

RESULTS

Activation of mTORC1 increased mitochondrial DNA expression, mitochondrial density and ATP production in pancreatic beta cells of βTSC2(-/-) mice. In TSC2 knockdown INS-1 cells, mitochondrial DNA expression, mitochondrial density and ATP production were increased compared with those in control INS-1 cells, consistent with the phenotype of βTSC2(-/-) mice. TSC2 knockdown INS-1 cells also exhibited augmented insulin secretory response to glucose. Rapamycin inhibited mitochondrial DNA expression and ATP production as well as insulin secretion in response to glucose. Thus, βTSC2(-/-) mice exhibit hyperinsulinemia due to an increase in the number of mitochondria as well as enlargement of individual beta cells via activation of mTORC1.

CONCLUSIONS

Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells.

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Text Mining Data

TSC2 → mTORC1: " Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells "

insulin → TSC2: " Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells "

insulin → mTORC1: " Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells "

Manually curated Databases

No curated data.