Effects of The Anti-glucagon Treatment (Amylin) on Isolated Hearts Performance in Experimentally Induced Type II Diabetes in Rats

Abstract

Background/Aims: Patients with type II diabetes (T2D) have underlying pathophysiological mechanisms that increase their cardiovascular disease risk. Anti-glucagon medications as amylin and its analogs are emerging antihyperglycemic agents which recently have gained attention. However, studies exploring cardiovascular effects of amylin have shown mixed outcomes. We, therefore, aimed to assess the effects of amylin on cardiac performance in experimentally induced T2D in rats. Methods: This study was carried out in a total duration of 5 weeks on 40 adult female Wistar Albino rats were allocated into 3 groups (control group, diabetic group and a group of diabetic rats treated with amylin). Rats in the diabetic and amylin treated groups were rendered diabetic by receiving high fat diet for 2 weeks, then subjected to a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in a dose of 35 mg/Kg dissolved in 1 mL of 0.05 M citrate buffer. Rats in the amylin group were treated with amylin which was started at the fifth week in a dose of 20 μg/Kg once daily for 7 days. ECG as well as the in vitro responses of isolated hearts to isoproterenol infusion by Langendorff’s preparation were also assessed. Blood samples were collected for biochemical measurements of fasting blood glucose, plasma insulin, glucagon, HbA1c and serum lipid profile. Results: Median baseline peak developed tension (PT) and PT per left ventricular weight (PT/LV) were significantly lowered in the diabetic group compared to the control group. Both parameters in the amylin treated group were significantly increased compared to the diabetic group and approached the normal control values. As regards cardiac responses to isoproterenol infusion, maximal and delta changes of heart rate (HR), PT and PT/LV were significantly decreased in the diabetic group compared to the control group. Whereas these parameters were significantly elevated in the amylin treated group compared to the diabetic group. Maximal and recovery HR values as well as maximal PT and PT/LV became normalized in the amylin treated group. The diabetic group also showed significant prolongation of time to peak tension (TPT), half relaxation time (HRT) and decrease of tension generation per unit time (TGPT), myocardial flow rate per left ventricular weight (MFR/LV) maximal responses to isoproterenol compared to control group. Those parameters were significantly improved in the amylin treated group and reached the control values, but the maximal responses of MFR/LV remained significantly lowered compared to the control group. Biochemically, amylin treatment lowered plasma glucagon level compared to diabetic and to control groups but did not increase plasma insulin level compared to diabetic group and remained significantly lowered compared to control group. Conclusions: Amylin, the anti-glucagon therapy, was able to impose partial improvement on cardiac chronotropic, inotropic functions and myocardial blood flow in diabetic state in response to beta adrenergic stimulation. Though, this improvement did not reach control levels and could be accounted for by glucagon lowering rather that due to insulin dependent mechanisms. Keywords