Aims
To explore the effect of octreotide on pancreatic fibrosis induced by high-fat diet (HFD) and its mechanism of action.
Background/aims
To explore the effect of octreotide on pancreatic fibrosis induced by high-fat diet (HFD) and its mechanism of action.
Conclusions
Octreotide can ameliorate pancreatic fibrosis and improve pancreatic beta-cell function induced in HFD treated rats, possibly by inhibiting PSC activation and by decreasing pancreatic extracellular matrix (ECM) through the TGF-β1/Smad signaling pathway.
Methods
Sprague-Dawley (SD) rats were assigned to control, HFD, or octreotide treatment groups. Glucose and insulin tolerance tests (GTT and ITT), fasting plasma glucose (FPG), and fasting insulin (FINS), serum and pancreatic lipid levels, were measured, and the Lee's index and the homeostatic model assessment (HOMA) index were calculated. The expression levels of alpha-smooth muscle actin (α-SMA), desmin, connective tissue growth factor (CTGF), transforming growth factor beta1 (TGF-β1), Smad3, and Smad7 in the pancreas were quantified. The LTC-14 cell line, which has features of primary rat pancreatic stellate cells (PSCs), was used for in vitro studies.
Results
The AUC of ipGTT and ipITT, and FPG, FINS, lipid levels, were elevated after HFD feeding; however, they decreased after octreotide administration. The expression of α-SMA, CTGF, TGF-β1, and Smad3 in the HFD group were increased relative to the control group, but Smad7 expression was decreased. After treatment with octreotide, α-SMA, CTGF, TGF-β1, and Smad3 expression decreased, whereas the expression of Smad7 increased. In vitro studies showed that the expression of CTGF, TGF-β1, and Smad3 increased with palmitate treatment (PA), which mimics HFD treatment; and octreotide treatment decreased the expression of these proteins. The α-SMA and Smad7 expression levels remained unchanged among the three groups. Conclusions: Octreotide can ameliorate pancreatic fibrosis and improve pancreatic beta-cell function induced in HFD treated rats, possibly by inhibiting PSC activation and by decreasing pancreatic extracellular matrix (ECM) through the TGF-β1/Smad signaling pathway.