Oleanolic acid and moderate drinking increase the pancreatic GLP-1R expression of the β-cell mass deficiency induced hyperglycemia.

Abstract

Oleanolic acid (OA) and moderate drinking have been reported to attenuate diabetes. However, the underlying mechanism of OA and moderate drinking alone or in combination on the islet β-cell deficiency induced diabetes is not fully elucidated. Male Sprague Dawley (SD) rats were intraperitoneally injected with 55 mg/kg streptozotocin (STZ) to induce β-cell deficiency. OA, 5% ethanol (EtOH), or a mixture of OA in 5% ethanol (OA+EtOH) were applied to three treatment groups of hyperglycemia rats for 6 weeks. STZ caused the increase of fast blood glucose (FBG) level.OA and EtOH treatment alone or in combination decreased the STZ increased FBG level during the 6 weeks of treatment. In addition, OA treatment also significantly increased the β-cell to total islet cell ratio. Both EtOH and OA+EtOH treatments promoted the increase of total islet cell number and α-cell to β-cell ratio when compared to OA group. STZ induced hyperglycemia dramatically reduced the glucagon-like peptide-1 receptor (GLP-1R) positive cells in islets, all the three treatments significantly increased the pancreatic GLP-1R positive cell number. In the meantime, STZ induced hyperglycemia suppressed the insulin mRNA expression and boosted the glucagon mRNA expression. EtOH and OA+EtOH treatments increased the insulin mRNA expression, but none of the 3 treatments altered the elevated glucagon level. GLP-1R positive cell ratio in islets is crucial for the blood glucose level of diabetes. OA and 5% ethanol alone or in combination suppresses the blood glucose level of β-cell deficiency induced diabetes by increasing islet GLP-1R expression.