Interactive effects of apelin, renin–angiotensin system and nitric oxide in treatment of obesity-induced type 2 diabetes mellitus in male albino rats

Abstract

Apelin and its receptor (APJ) are involved in the regulation of a variety of pathophysiological processes. We studied the effect of apelin treatment on obesity-induced type 2 diabetes mellitus (T2DM) and possible interaction between apelin/APJ system and renin-angiotensin system (RAS). Forty eight male albino rats were divided into two groups: control group and diabetic group. Diabetic group was subdivided into: control diabetic, apelin-treated, apelin + losartan-treated, apelin + l-NAME-treated and losartan-treated diabetic subgroup. Administration of apelin-13 yielded an improvement of IR, dyslipidaemia, inflammation, oxidative stress with significant decrease in AT1R gene expression and significant increase in ACE2 gene expression in adipose tissues. Losartan + apelin yielded a further significant decrease in ATR1 gene expression, glycaemic indices, serum TGs and TPA versus Apelin only. Adding l-NAME in subgroup (2D) reversed the effect of apelin. We suggested that the beneficial effect of Apelin is mainly mediated by NO-activated pathway and/or ACE2/Ang (1-7) dependent pathway.

Overexpression of angiotensin-converting enzyme 2 by renin-angiotensin system inhibitors. Truth or myth? A systematic review of animal studies

“…In STZ-induced diabetic rats fed a high-fat, high-sucrose diet, visceral fat ACE2 mRNA was repressed and slightly attenuated to within the repression level by losartan (Fig. 5) [106]. In subcutaneous fat, a high-fat diet repressed ACE2 mRNA, which was reversed to the no/marginal change level by telmisartan [36].…”

Apelin‑13 alleviates diabetic nephropathy by enhancing nitric oxide production and suppressing kidney tissue fibrosis

“…However, in the field of diabetic nephropathy, a recent study reported that the levels of apelin and its receptor APJ in the serum of patients with diabetic nephropathy were increased, and higher levels of apelin and APJ promoted blood vessel formation and induced the proliferation of glomerular capillaries, thereby promoting the occurrence and development of diabetic nephropathy ( 29 ). However, a different study also indicated that apelin-13 could inhibit the transformation of renal tubular epithelial cells in a high-glucose environment, thereby inhibiting the occurrence and development of the EMT process in glomerular cells, ultimately delaying the occurrence of diabetic nephropathy ( 30 ). In the present study, it was demonstrated that the use of apelin-13 decreased the levels of blood glucose and relieved insulin resistance in these rats, as well as reduced the urinary protein content.…”

Potential Therapeutic Role for Apelin and Related Peptides in Diabetes: An Update

“…administration of apelin-13 (0.1 µmol/kg bw) for 6 weeks improved insulin sensitivity and reduced blood glucose concentrations in high fat fed diabetic rats (T2DM model). 62 Furthermore, (pGlu)apelin-13 has also been shown to dose-dependently increase glucose uptake in ex vivo human adipose tissue via 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. 63 In agreement, apelin-13 has previously been shown to improve glucose tolerance in normal mice as well as augment glucose uptake in insulin-resistant high fat fed mice.…”