Nuclear SREBP-1a causes loss of pancreatic {beta}-cells and impaired insulin secretion

Journal Article · Fri Jan 16 04:00:00 EST 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.11.105· OSTI ID:21255838

Iwasaki, Yuko; Iwasaki, Hitoshi; Yatoh, Shigeru; Ishikawa, Mayumi; Kato, Toyonori; Matsuzaka, Takashi; Nakagawa, Yoshimi; Yahagi, Naoya; Kobayashi, Kazuto; Takahashi, Akimitsu; Suzuki, Hiroaki; Yamada, Nobuhiro ^[1]; Shimano, Hitoshi ^[1]

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1. Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

Transgenic mice expressing nuclear sterol regulatory element-binding protein-1a under the control of the insulin promoter were generated to determine the role of SREBP-1a in pancreatic {beta}-cells. Only low expressors could be established, which exhibited mild hyperglycemia, impaired glucose tolerance, and reduced plasma insulin levels compared to C57BL/6 controls. The islets isolated from the transgenic mice were fewer and smaller, and had decreased insulin content and unaltered glucagon staining. Both glucose- and potassium-stimulated insulin secretions were decreased. The transgenic islets consistently expressed genes for fatty acids and cholesterol synthesis, resulting in accumulation of triglycerides but not cholesterol. PDX-1, {beta}{epsilon}{tau}{alpha}2, MafA, and IRS-2 were suppressed, partially explaining the loss and dysfunction of {beta}-cell mass. The transgenic mice on a high fat/high sucrose diet still exhibited impaired insulin secretion and continuous {beta}-cell growth defect. Therefore, nuclear SREBP-1a, even at a low level, strongly disrupts {beta}-cell mass and function.

• OSTI ID: 21255838
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 378; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARBOXYLIC ACIDS
CHOLESTEROL
DIET
GENES
GLUCAGON
GLUCOSE
HYPERGLYCEMIA
INSULIN
PANCREAS
PROMOTERS
SACCHAROSE
SECRETION
TRANSCRIPTION FACTORS
TRANSGENIC MICE
TRIGLYCERIDES