The aim of the present study is to evaluate the prophylactic effect of Sitagliptin, Pioglitazone and Dapagliflozine on Isoprenaline induced myocardial infarction in type II diabetic rats.

The American Diabetes Association defined diabetes mellitus as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction and failure of different organs, especially the eyes, kidneys, nerves, heart and blood vessels.

Myocardial ischemia represents a condition of sufferance for cardiomyocytes due to coronary blood flow reduction as compared to their metabolic needs, and it may exhibit through several clinical conditions.

People with type 2 diabetes mellitus are at increased risk of cardiovascular disease, heart failure and death, as compared with the general population. Studies show that the excess risks associated with diabetes mellitus are mediated primarily by hyperglycemia and overall poor risk factor control. Effective treatment of traditional cardiovascular risk factors has reduced the excess risk of atherosclerotic cardiovascular disease , such as acute myocardial infarction and stroke in people with type 2 diabetes mellitus.

In the last two decades, several studies have demonstrated reductions in the risk of cardiovascular outcomes and mortality in patients with type 2 diabetes mellitus with improved glucose and cholesterol-lowering therapies. Nevertheless, macrovascular disease remains the most common cause of death in type 2 diabetes mellitus patients and new diabetes therapies are highly desired, especially if they can offer cardiovascular benefits.

Sitagliptin is a potent and highly selective dipeptidyl peptidase-4 competitive inhibitor that does not affect the closely related enzymes dipeptidyl peptidase-8 or dipeptidyl peptidase-9 at therapeutic concentrations.

Sitagliptin found to enhance circulating glucagon-like peptide-1 levels through inhibition of dipeptidyl peptidase -IV activity.

which, in turn, provides cardiovascular protection probably through the anti-inflammatory and anti-atherosclerotic activities of glucagon-like peptide-1. Reduces blood glucose levels, in either the postprandial or the fasting state.

Multiple studies have suggested that pioglitazone, a peroxisome proliferatoractivated receptor γ agonist, used as an insulin-sensitizing agent in the treatment of type 2 diabetes mellitus , may have anti-atherosclerotic effects.

The mechanism of action of dapagliflozine influences a number of cardiovascular disease risk factors, in particular, decreasing blood pressure, reducing body weight (predominantly through reductions in total body fat mass, including visceral adipose tissue), reducing waist circumference, and lowering albuminuria and serum uric acid levels, with allow intrinsic risk of hypoglycemia.

Isoprenaline is a potent β-adrenergic agonist, increases the myocardial oxygen demand by mixture of its positive inotropic and chronotropic actions. Administration of isoprenaline in high doses to animals produces infarct like lesions in the heart similar to those present in myocardial infatction in humans.

The aim of the present study is to evaluate the prophylactic effect of Sitagliptin, Pioglitazone and Dapagliflozine on Isoprenaline induced myocardial infarction in type II diabetic rats.

Inclusion Criteria:

• 50 adult male albino rats obtained from (Experimental Animal Breeding Farm, assuit -Cairo) weighing between 150- 200 g (at the beginning of the study)

Exclusion Criteria:

• Female rats --Weight >200g