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The effect of glucagon-like peptide-1 in the management of diabetes mellitus: cellular and molecular mechanisms

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Abstract

Incretins, such as glucagon-like peptide-1 (GLP)-1, have been shown to elevate plasma insulin concentration. The purpose of this study is to investigate the cellular and molecular basis of the beneficial effects of GLP-1. Normal and diabetic male Wistar rats were treated with GLP-1 (50 ng/kg body weight) for 10 weeks. At the end of the experiment, pancreatic tissues were taken for immunohistochemistry, immunoelectron microscopy and real-time polymerase chain reaction studies. Samples of blood were retrieved from the animals for the measurement of enzymes and insulin. The results show that treatment of diabetic rats with GLP-1 caused significant (P < 0.05) reduction in body weight gain and blood glucose level. GLP-1 (10−12–10−6 M) induced significant (P < 0.01) dose-dependent increases in insulin release from the pancreas of normal and diabetic rats compared to basal. Diabetes-induced abnormal liver (aspartate aminotransferase and alanine aminotransferase) and kidney (blood urea nitrogen and uric acid) parameters were corrected in GLP-1-treated rats compared to controls. GLP-1 treatment induced significant (P < 0.05) elevation in the expression of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and GLP-1-receptor genes in diabetic animals compared to controls. GLP-1 is present in pancreatic beta cells and significantly (P < 0.05) increased the number of insulin-, glutathione reductase- and catalase-immunoreactive islet cells. The results of this study show that GLP-1 is co-localized with insulin and seems to exert its beneficial effects by increasing cellular concentrations of endogenous antioxidant genes and other genes involved in the maintenance of pancreatic beta cell structure and function.

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Abbreviations

DM:

Diabetes mellitus

DPP-4:

Dipeptide peptidase-IV

ELISA:

Enzyme-linked immunosorbent assay

EM:

Electron microscopic

GI:

Gastrointestinal

GLP-1:

Glucagon-like peptide-1

GLP-1r:

Glucagon-like peptide-1 receptor

GPx:

Glutathione peroxidase

GSR:

Glutathione Reductase

HSP-70:

Heat shock protein-70

IPGTT:

Intraperitoneal glucose tolerance test

ROS:

Reactive oxygen species

RT-PCR:

Real time-polymerase chain reaction

SEM:

Standard error of the mean

STZ:

Streptozotocin

T1DM:

Type 1 DM

T2DM:

Type 2 DM

UAEU:

United Arab Emirates University

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Acknowledgments

The project was supported by a grant from the United Arab Emirates University.

Conflicts of interest

None.

Author contributions

ML, JS and EA planned and wrote the manuscript. HR played a major role in the in vitro study and immunohistochemistry. ST made contribution to the transmission electron microscopy section and EZ played a major role in the gene expression study.

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Authors and Affiliations

  1. Department of Biology, College of Science, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates

    Mohamed Lotfy

  2. Hormones Department, National Research Centre, Cairo, Egypt

    Mohamed Lotfy

  3. School of Forensic and Investigative Sciences and School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, England, UK

    Mohamed Lotfy & Jaipaul Singh

  4. Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box17666, Al Ain, United Arab Emirates

    Hameed Rashed, Saeed Tariq & Ernest Adeghate

  5. Department of Medical Microbiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

    Erika Zilahi

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  1. Mohamed Lotfy
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  2. Jaipaul Singh
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  3. Hameed Rashed
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  4. Saeed Tariq
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  6. Ernest Adeghate
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Correspondence to Ernest Adeghate.

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Lotfy, M., Singh, J., Rashed, H. et al. The effect of glucagon-like peptide-1 in the management of diabetes mellitus: cellular and molecular mechanisms. Cell Tissue Res 358, 343–358 (2014). https://doi.org/10.1007/s00441-014-1959-9

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  • DOI: https://doi.org/10.1007/s00441-014-1959-9

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