One of the new promising therapies in treatment of diabetes mellitus is mesenchymal stem cells (MSCs) which have
an interesting therapeutic potentiality based on their paracrine effect and transdifferentiation potentiality. Also obestatin
improves the generation of functional β cells/islet-like cell clusters in vitro, suggesting implications for cell-based
replacement therapy in diabetes. So the aim of this study was to evaluate the effect of combination of both MSCs
and obestatin on an experimental model of type II diabetes mellitus (T2DM). Sixty male rats were divided into; group
I (control group), group II (T2DM group) induced by administration of high fat diet (HFD) and injection of streptozotocin
(STZ) in low dose, group III (T2DM treated with MSCs), group IV (T2DM treated with obestatin), group V
(T2DM treated with MSCs and obestatin). Fasting blood glucose, C-peptide, insulin and lipid profile were measured.
HOMA-IR and HOMA-β were calculated. Pancreatic expression of insulin, glucagon like peptide -1 (GLP-1) and pancreatic
duodenal homeobox 1 (Pdx1) mRNA levels were measured. In addition pancreatic histological changes, insulin
and Bax were analyzed by immunohistochemical examination of islets of Langerhans. Diabetic rats showed significant
increase in HOMA-IR, serum glucose and lipid profile levels with significant decrease in insulin, HOMA-β, GLP-1
and Pdx1 levels. MSCs and obestatin caused significant improvement in all parameters with more significant improvement
in combined therapy. The protective effects afforded by MSCs and obestatin may derive from improvement of
the metabolic profile, antiapoptosis and by increase in pancreatic GLP-1and Pdx1 gene expression.