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Exp Clin Endocrinol Diabetes 2016; 124(04): 239-245
DOI: 10.1055/s-0035-1569356
Article
© Georg Thieme Verlag KG Stuttgart · New York

Peptide Binding Glucose Regulated Protein 78 Improves Type 1 Diabetes by Preventing Pancreatic β Cell Apoptosis

A. Raiter   *
1   Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel.
3   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
A. Tenenbaum   *
2   The Jesse Z and Sara Lea Shafer, Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
3   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
M. Yackobovitch-Gavan
2   The Jesse Z and Sara Lea Shafer, Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
,
A. Battler
1   Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel.
3   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
B. Hardy
1   Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel.
3   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
› Author Affiliations
Further Information

Publication History

received 21 September 2015
first decision 16 November 2015

accepted 09 December 2015

Publication Date:
28 April 2016 (online)

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Abstract

Background and Objectives: Diabetes Type 1 is characterized by hyperglycemia due to reduced insulin secretion that results from the death of pancreatic β cells. It was suggested that endoplasmic reticulum (ER) stress is associated with the autoimmune-mediated β cell destruction. Glucose regulated protein 78 (GRP78) functions as a key regulator to maintain the ER function. Under stress conditions GRP78 is up-regulated and expressed on the cell surface serving as a signaling receptor. Our first objective was to examine the effects of peptide binding cell surface GRP78 to reduce the deleterious effects of diabetes induced by streptozotocin. The second objective was to demonstrate the ability of the peptide to protect the pancreatic β cells from apoptosis.

Methods: The effect of ADoPep on weight loss, HbA1c levels and anti GRP78 antibody titers was evaluated in a diabetes mouse model. The effect of ADoPep on the pancreatic β Ins1E cell apoptosis was determined by FACS analysis.

Results: The administration of ADoPep to diabetic mice retained the weight loss and reduced HbA1c significantly in 60% of mice. Titers of anti GRP78 antibodies increased in 70% of the treated mice. Apoptosis was significantly inhibited in stressed pancreatic β Ins 1E cells.

Conclusions: We demonstrate that administration of the peptide ADoPep to diabetic mice improved type 1 diabetes by preventing pancreatic β cell apoptosis.

Key words

ADoPep peptide - apoptosis - diabetes type 1 - GRP78 - pancreatic β cells - streptozotocin mouse model

* Raiter A and Tenenbaum A contributed equally to this manuscript.


 

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