GLP-1(28-36) improves [Beta]-cell mass and glucose disposal in streptozotocin-induced diabetic mice and activates cAMP/PKA/[Beta]-catenin signaling in [Beta]-cells in vitro

Recent studies have demonstrated that the COOH-terminal fragment of the incretin hormone glucagon-like peptide-1 (GLP-1), a nonapeptide GLP-1(28-36)amide, attenuates diabetes and hepatic steatosis in diet-induced obese mice. However, the effect of this nonapeptide in pancreatic β-cells remains large...

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Bibliographic Details
Published in:American journal of physiology: endocrinology and metabolism 2013-06, Vol.304 (12), p.E1263
Main Authors: Shao, Weijuan, Wang, Zhaoxia, Ip, Wilfred, Chiang, Yu-Ting, Xiong, Xiaoquan, Chai, Tuanyao, Xu, Catherine, Wang, Qinghua, Jin, Tianru
Format: Article
Language:English
Subjects:
Cells
Diabetes
Glucose
Phosphorylation
Proteins
Rodents
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Summary:Recent studies have demonstrated that the COOH-terminal fragment of the incretin hormone glucagon-like peptide-1 (GLP-1), a nonapeptide GLP-1(28-36)amide, attenuates diabetes and hepatic steatosis in diet-induced obese mice. However, the effect of this nonapeptide in pancreatic β-cells remains largely unknown. Here, we show that in a streptozotocin-induced mouse diabetes model, GLP-1(28-36)amide improved glucose disposal and increased pancreatic β-cell mass and β-cell proliferation. An in vitro investigation revealed that GLP-1(28-36)amide stimulates β-catenin (β-cat) Ser... phosphorylation in both the clonal INS-1 cell line and rat primary pancreatic islet cells. In INS-1 cells, the stimulation was accompanied by increased nuclear β-cat content. GLP-1(28-36)amide was also shown to increase cellular cAMP levels, PKA enzymatic activity, and cAMP response element-binding protein (CREB) and cyclic AMP-dependent transcription factor-1 (ATF-1) phosphorylation. Furthermore, GLP-1(28-36)amide treatment enhanced islet insulin secretion and increased the growth of INS-1 cells, which was associated with increased cyclin D1 expression. Finally, PKA inhibition attenuated the effect of GLP-1(28-36)amide on β-cat Ser... phosphorylation and cyclin D1 expression in the INS-1 cell line. We have thus revealed the beneficial effect of GLP-1(28-36)amide in pancreatic β-cells in vitro and in vivo. Our observations suggest that GLP-1(28-36)amide may exert its effect through the PKA/β-catenin signaling pathway. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0193-1849
1522-1555