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.