Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC222
The beneficial effect of GLP-1 treatment in type 1 diabetic rats
M. Lotfy2, J. Singh3,4, E. Adeghate1
1. Anatomy, Faculty of Medicine, UAE University, Al Ain, United Arab Emirates. 2. Biology, Faculty of Science, UAE University, Al Ain, United Arab Emirates. 3. School of Pharmacy, University of Central Lancashire, Preston, United Kingdom. 4. School of Forensic and Investigative Sciences, University of Central Lancashire, Preston, United Kingdom.
Diabetes mellitus is a major metabolic disorder resulting in numerous long-term complications. Factors that can reduce these complications and increase the ability of pancreatic islets cells to secrete insulin are of tremendous benefit to diabetic patients. This study investigated the beneficial effects of glucagon-like peptide-1 (GLP-1) on streptozotocin (STZ)-induced type 1 diabetic rats compared to healthy, age-matched controls. The study employed four groups of rats (2 age-matched controls; 2 rendered diabetic using a single intraperitoneal (i.p.) injection of STZ (60 mg kg-1)). Two groups of rats (either control or diabetic) were untreated while rats from the other two groups were given GLP-1 (50 nmol/kg body weight i.p.) for 10 weeks. The project had the relevant ethical clearance from the Ethics Committees of both UCLAN and UAE University to undertake the study. GLP-1 can evoke significant (Student’s t-test, p<0.05) increases (7.4±0.4 for GLP-1-treated controls vs. 5.9±0.3 for untreated controls compared to 4.8±0.1 for GLP-1-treated diabetic vs.3.5±0.2 for untreated diabetic rats)in serum insulin (µlUml-1)in both normal and diabetic-treated rats compared to untreated animals. Immnohistochemistry shows significant increases (in percentages)in (a) the number of insulin-positive cells (84.9±1.1 for GLP-1-treated vs. 80.2±1.3 for untreated controls;p< 0.05, compared to 32.0±1.7 for GLP-1-treated diabetic vs. 7.9± 0.7 for untreated diabetic rats; p<0.001),(b)catalase-positive cells (98.0±0.8 for GLP-1-treated controls vs. 95.0±1.0 for untreated controls compared to 87.2±1.3 for GLP-1-treated diabetic vs. 66.3±2.9 for untreated diabetic rats; p<0.001) and (c) glutathione reductase-positive cells (96.0±1.3 for GLP-1-treated controls vs. 93.0±1.1 for untreated controls compared to 88.4±2.0 for GLP-treated diabetic vs. 66.2±3.7 for untreated diabetic rats; p<0.001). Gene expression studies show significant increases [relative quantification (RQ)]in the levels of mRNAs for (a) pancreatic duodenal homeobox-1 (0.28±0.01 for GLP-1-treated controls vs.0.22 ± 0.01 for untreated controls; p<0.05, compared to 1.9±0.45 in GLP-treated diabetic vs. 0.69±0.2 for untreated diabetic rats; p<0.05), (b) heat shock protein-70 (1.44±0.11 for GLP-1-treated controls vs. 0.93±0.12 for untreated control rats; p<0.05, compared to 1.05±0.08 for GLP-1-treated diabetic vs. 0.69±0.11 for untreated diabetic rats; p<0.05) and (c) insulin receptor (0.71±0.06 for GLP-1-treated controls vs. 0.58±0.11 for untreated control rats compared to 1.56±0.15 for GLP-1-treated diabetic vs. 1.03±0.07 for untreated diabetic rats; p<0.01). The results have shown that GLP-1 may have beneficial effects on beta-cells since it can evoke significant increases in the level of antioxidant enzymes in pancreatic islet cells of diabetic rats. GLP-1 seems to repair the damaged beta cells of diabetic rats via its effects on insulin metabolism at the molecular level.
Where applicable, experiments conform with Society ethical requirements