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Cited by 62Pancreatic function and diabetesEndoplasmic Reticulum Stress and DiseaseDiabetes Treatment and Management

Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice

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Kato, Toyonori, Shimano, Hitoshi, Yamamoto, Takashi, Yokoo, Tomotaka, Endo, Yuko, Ishikawa, Mayumi, Matsuzaka, Takashi, Nakagawa, Yoshimi +11 more·2006·Cell Metabolism
DOI 10.1016/j.cmet.2006.06.009
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Abstract

Granuphilin is a crucial component of the docking machinery of insulin-containing vesicles to the plasma membrane. Here, we show that the granuphilin promoter is a target of SREBP-1c, a transcription factor that controls fatty acid synthesis, and MafA, a beta cell differentiation factor. Potassium-stimulated insulin secretion (KSIS) was suppressed in islets with adenoviral-mediated overexpression of granuphilin and enhanced in islets with knockdown of granuphilin (in which granuphilin had been knocked down). SREBP-1c and granuphilin were activated in islets from beta cell-specific SREBP-1c transgenic mice, as well as in several diabetic mouse models and normal islets treated with palmitate, accompanied by a corresponding reduction in insulin secretion. Knockdown- or knockout-mediated ablation of granuphilin or SREBP-1c restored KSIS in these islets. Collectively, our data provide evidence that activation of the SREBP-1c/granuphilin pathway is a potential mechanism for impaired insulin secretion in diabetes, contributing to beta cell lipotoxicity.

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  • Long-term (48 h) exposure of pancreatic islets to palmitate increases Sytl4 expression and inhibits insulin secretion.

    “Long-term (48h) exposure of pancreatic islets to the non-esterified free fatty acid (NEFA) palmitate has been reported to increase Sytl4 expression and inhibit insulin secretion (342).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [342]

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Authors
Kato, T., Shimano, H., Yamamoto, T., Yokoo, T., Endo, Y., Ishikawa, M., Matsuzaka, T., Nakagawa, Y., Kumadaki, S., Yahagi, N., Takahashi, A., Sone, H., Suzuki, H., Toyoshima, H., Hasty, A. H., Takahashi, S., Gomi, H., Izumi, T., & Yamada, N.
Affiliations
  • University of Tsukuba (JP)
  • Vanderbilt University Medical Center (US)
  • Gunma University (JP)
Corresponding author
Shimano, Hitoshi
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2006-08
Volume
4
Issue
2
Pages
143-154
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2006.06.009
OpenAlex
W2032505777
Cited by
62
References
2
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 2
FWCI
8.76
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
SREBP-1c, MafA, insulin secretion, diabetes mellitus, pancreatic islets, palmitate, transcriptional regulation
MeSH terms
Insulin Secretion, Animals, Cells, Cultured, Diabetes Mellitus, Experimental, Insulin, Islets of Langerhans, Male, Mice, Inbred C57BL, Mice, Transgenic, Palmitates, Potassium, Promoter Regions, Genetic, Signal Transduction, Mice, Inbred NOD, Vesicular Transport Proteins, Mice, Maf Transcription Factors, Large, Sterol Regulatory Element Binding Protein 1

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