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PGLP‐1, a novel long‐acting dual‐function GLP‐1 analog, ameliorates streptozotocin‐induced hyperglycemia and inhibits body weight loss
Author(s) -
Gao Huashan,
Zhao Qian,
Song Ziwei,
Yang Zhaocong,
Wu You,
Tang Shanshan,
Alahdal Murad,
Zhang Yanfeng,
Jin Liang
Publication year - 2017
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/fj.201700002r
Subject(s) - streptozotocin , glucagon like peptide 1 , endocrinology , medicine , in vivo , glucagon like peptide 1 receptor , insulin , agonist , receptor , chemistry , weight loss , diabetes mellitus , pharmacology , type 2 diabetes , biology , obesity , microbiology and biotechnology
It is well known that glucagon‐like peptide 1 (GLP‐1) has antidiabetic action. It has 2 distinct functions, an insulinotropic effect dependent on GLP‐1 receptor (GLP‐1R) and an insulinomimetic effect independent of GLP‐1R. However, use of GLP‐1 in vivo is limited by its short half‐life. Therefore, our lab designed PGLP‐1, a novel 2‐function candidate peptide as a potential substitute. Using a streptozotocin‐induced hyperglycemic mouse model, we demonstrated in vitro and in vivo that PGLP‐1 had insulinotropic actions dependent on GLP‐1R and insulinomimetic functions independent of GLP‐1R. PGLP‐1 treatment increased islet β‐cell mass, plasma insulin, and C‐peptide levels and Ki‐67‐immunoreactive β‐cell numbers, verifying that PGLP‐1 can work as a short GLP‐1R agonist, similar to commercially available exendin‐4. Additionally, PGLP‐1 improved insulin sensitivity, inhibited gluconeogenesis by increasing expression of AMPK and receptor subfamily 0, group B, member 2 (SHP), and inhibited body weight loss by inhibiting β‐oxidation, suggesting that PGLP‐1 had insulinomimetic action. Taken together, these data indicated that PGLP‐1, as a dual‐function peptide, improved glycemic control and inhibited body weight loss, suggesting it could be useful for type 1 diabetes mellitus patients as an adjunctive therapy to insulin.—Gao, H., Zhao, Q., Song, Z., Yang, Z., Wu, Y., Tang, S., Alahdal, M., Zhang, Y., Jin, L. PGLP‐1, a novel long‐acting dual‐function GLP‐1 analog, ameliorates streptozotocin‐induced hyperglycemia and inhibits body weight loss. FASEB J . 31, 3527–3539 (2017). www.fasebj.org