The dipeptidyl peptidase-4 inhibitor teneligliptin improved endothelial dysfunction and insulin resistance in the SHR/NDmcr-cp rat model of metabolic syndrome

Abstract

Diabetes mellitus, hypertension and metabolic syndrome are major risk factors for the occurrence of cardiovascular events. In this study, we used spontaneous hypertensive rat (SHR)/NDmcr-cp (cp/cp) (SHRcp) rats as a model for metabolic syndrome to examine the effects of dipeptidyl peptidase (DPP)-4 inhibition on hypertension, glucose metabolism and endothelial dysfunction. First, we confirmed that SHRcp rats showed very severe obesity, hypertension and endothelial dysfunction phenotypes from 14 to 54 weeks of age. Next, we examined whether the DPP-4 inhibitor teneligliptin (10 mg kg(-1) per day per os for 12 weeks) could modify any of these phenotypes. Treatment with teneligliptin significantly improved hyperglycemia and insulin resistance, as evidenced by an oral glucose tolerance test and homeostasis model assessment for insulin resistance, respectively. Teneligliptin showed no effects on systolic blood pressure or heart rate. In regard to endothelial function, the vasodilator response to acetylcholine was significantly impaired in SHRcp rats when compared with WKY rats. Long-term treatment with teneligliptin significantly attenuated endothelial dysfunction through the upregulation of endothelium-derived nitric oxide synthase mRNA. These results demonstrate that long-term treatment with teneligliptin significantly improved endothelial dysfunction and glucose metabolism in a rat model of metabolic syndrome, suggesting that teneligliptin treatment might be beneficial for patients with hypertension and/or diabetes.

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, suppresses CXCL5 and SDF-1 and does not accelerate intestinal neoplasia formation in ApcMin/+ mice fed a high-fat diet

“…However, in the present study, long-term treatment with STG in conditionally obese mice paradoxically suppressed chemokines associated with obesity. Since it has been reported that the administration of SPP-4 inhibitor improved insulin resistance and lipid metabolism (31,32), it was hypothesized that the long term administration of STG improved the metabolic status of mice fed a HFD, and as a result the expression of these chemokines was decreased.…”

Anagliptin increases insulin-induced skeletal muscle glucose uptake via an NO-dependent mechanism in mice

“…Nakagami et al previously demonstrated using a spontaneously hypertensive corpulent congenic (SHR)/NDmcr-cp rat model that DPP-4 inhibitors improved endothelial function [38]. This rat model, a spontaneously hypertensive strain with a nonsense mutation in the leptin receptor, shows obesity, severe hypertension, insulin resistance, hyperglycaemia, increased levels of inflammatory cytokines and hyperlipidaemia.…”

Teneligliptin, a Chemotype Prolyl-Thiazolidine-Based Novel Dipeptidyl Peptidase-4 Inhibitor with Insulin Sensitizing Properties

“…However, their involvement in insulin resistance (or sensitivity), another hallmark for blood glucose regulatory mechanism, remains elusive. Very recently, teneligliptin, a chemotype prolylthiazolidine-based novel DPP-4 inhibitor [3][4][5][6][7][8], was preliminarily shown to reduce insulin resistance in patients with type 2 diabetes mellitus (T2DM) [9,10] and in an animal model [11].…”