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We analyzed the effects of tight glycemic control on regenerative potential of myocardium during acute myocardial infarction.Seventy-five patients with their first acute myocardial infarction undergoing coronary bypass surgery were studied: 25 patients with glycemia below 140 mg/dl served as the control group; hyperglycemic patients (glucose >140 mg/dl) were randomized to intensive glycemic control (IGC; n = 20; glucose goal, 80–140 mg/dl), conventional glycemic control (CGC; n = 20; glucose goal, 180–200 mg/dl), or glucose-insulin-potassium (GIK; n = 10; glucose goal, 180–200 mg/dl) for almost 3 d before surgery, using insulin infusion followed by sc insulin treatment. During surgery, myocyte precursor cells (MPC) (c-kit/MEFC2/GATA4-positive cells), oxidation of MPC DNA (c-kit/8-hydroxydeoxyguanosine-positive cells), senescent MPC (c-kit/p16INK4a-positive cells), and cycling cardiomyocytes (Ki-67-positive cells) were analyzed in biopsy specimens taken from the peri-infarcted area.Before surgery, plasma glucose reduction was greater in the IGC group than in the CGC and GIK groups (P < 0.001 for both). IGC patients had higher MPC (P < 0.01) and cycling myocytes (P < 0.01), as well as less oxidized (P < 0.01) and senescent MPC (P < 0.01) in peri-infarcted specimens compared with both CGC and GIK patients. Tight glycemic control, by reducing senescent MPC, may increase regenerative potential of the ischemic myocardium.