LINAGLIPTIN AMELIORATES HEPATIC DERANGEMENT AND ENDOTHELIAL DYSFUNCTION IN TYPE 2 DIABETIC RATS: BIOCHEMICAL, FUNCTIONAL AND HISTO-MORPHOMETRIC ANALYSIS

Hazem F. Mannaa*, Tarek A. Abd Allah, Wafaa A. Hewedy, Eiman I. Zaki, Salma H. Kandiel

ABSTRACT

Introduction: Management of diabetes mellitus and its complications remains a worldwide health challenge. Type 2 diabetes mellitus (T2DM) is linked to wide arrays of macrovascular and microvascular complications; where endothelial dysfunction plays the primary step in their development. T2DM is also accompanied by variable liver-related complications; regardless of the glycemic control. The formation of advanced glycation end-products (AGEs) is recognized as a key factor in the development of many diabetic complications. Aim: The current study was designed to evaluate the possible hepatoprotective and vascular protective effects of linagliptin in a rat model of T2DM. Material and methods: DM was induced by a combination of high-fat diet administration and a single intraperitoneal injection of streptozotocin. Serum metabolic indices, liver lipid contents, liver function tests and serum advanced glycation end products (AGEs) were determined. Sections of the liver were used for histological and morphometric analysis. The response of aortic ring preparations to different doses of norepinephrine and acetylcholine, in vitro, was also evaluated. Results: Linagliptin significantly attenuated fasting blood glucose, plasma insulin, insulin resistance, serum lipids and hepatic contents of cholesterol and triglyceride compared to the diabetic rats. It also reverted the liver near normal structure. Moreover, linagliptin treatment improved the impaired relaxations of aortic rings of diabetic animals. Conclusion: Linagliptin treatment can ameliorate hepatic derangement, endothelial dysfunction in this animal model of type 2 diabetes.

Keywords: Advanced glycation end products; endothelial dysfunction; fatty liver; linagliptin.