Selective somatostatin receptor 5 inhibition improves hepatic insulin sensitivity

In conclusion, selective SSTR5 inhibition can improve insulin sensitivity by enhancing liver insulin action. AbstractDiabetes is a metabolic disorder with an increasing global prevalence. Somatostatin (SST), a peptide hormone, regulates hormone secretion via five SST receptor (SSTR) subtypes (SSTR1 –5) in a tissue-specific manner. As SSTR5 is expressed in pancreatic β-cells and intestinal L-cells, studies have suggested that SSTR5 regulates glucose tolerance through insulin and incretin secretion, thereby having a prominent role in diabetes. Moreover, SSTR5 knockout (KO) mice display enhanc ed insulin sensitivity; however, the underlying mechanism has not been clarified. Therefore, in this study, we investigate the effect of SSTR5 blockade on insulin resistance and the target organ using SSTR5 KO mice and a selective SSTR5 antagonist (compound-1). High-fat diet (HFD)-fed SSTR5 KO mice exhibited significantly lower homeostasis model assessment of insulin resistance (HOMA-IR) than HFD-fed wild-type mice. Two-week oral administration of compound-1 dose-dependently and significantly reduced changes in the levels of glycosylated hemoglobin (GHb), plasma glucose, plasma insulin, and HO MA-IR in male KK-Ay/Ta Jcl mice (KK-Ay mice), a model of obese type 2 diabetes with severe insulin resistance. Additionally, compound-1 significantly increased the glucose infusion rate while decreasing hepatic glucose production in male KK-Ay mice, as evidenced by hyperinsulinemic-euglycemic clam...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research