Premium
Enhanced islet neogenesis and beta‐cell proliferation in pre‐insulitic diabetes‐prone rats fed a hydrolyzed casein diet
Author(s) -
Wang GenSheng,
Kauri Lisa M.,
Patrick Christopher,
Scott Fraser W.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a771-a
Subject(s) - neogenesis , islet , medicine , endocrinology , downregulation and upregulation , beta cell , diabetes mellitus , insulin , biology , chemistry , biochemistry , gene
Diabetes incidence is reduced in diabetes‐prone BioBreeding (BBdp) rats fed a hydrolyzed casein (HC) diet compared with a standard cereal‐based rodent diet such as NTP‐2000 (NTP). To further characterize the basis of this protective effect, islet neogenesis, apoptosis and cell proliferation were analyzed using immunohistochemistry, morphometry, Laser Capture Microdissection, and RT‐PCR in BBdp rats weaned onto an NTP or HC diet at 23 d and sacrificed at 25, 30, and 45 d. Islet area fraction was greater in medium and large islets of HC‐fed rats at 30 d and in large islets only at 45 d. There were more small islets in HC‐fed rats both at 30 and 45 d and β‐cell mass was significantly greater at 45 d. Cell cycle analysis revealed an increased ratio of S+G2/G0+G1 in HC‐fed animals between 25 and 45 d. PDX‐1 + clusters (<4 cells) were increased in HC‐fed rats, whereas extra‐islet insulin + clusters (EIC) and insulin + cells in ducts, representative of islet neogenesis, were increased at 45 d. Ngn3 mRNA was higher in EIC of HC‐fed rats at 24 d. Glucagon‐like peptide‐1 receptor protein and mRNA were increased in islets of HC‐fed rats. In summary, the protective HC diet increased β‐cell mass in diabetes‐prone rats through upregulation of islet neogenesis and β‐cell proliferation. (GSW and LMK contributed equally; Supported by Canadian Diabetes Association and Canadian Institutes of Health Research)