Objective: Hypoglycemic damage to the central nervous system is well known
complication of insulin therapy. Little is known about the effect of insulin induced
hypoglycemia on peripheral tissues as skeletal muscles and heart. In the present
study the effect of acute and recurrent insulin- induced hypoglycemia on plasma
creatine kinase (CK) and Lactate dehydrogenase (LDH); markers of skeletal muscles
and heart damage was studied. Oxidative stress in those tissues and plasma
epinephrine levels after hypoglycemia were also evaluated to elucidate the
mechanism of hypoglycemic effect on those tissues. Methods: The study consisted of
50 adult male rats divided into three groups: (1) Control group. (2) Acute insulininduced
hypoglycemia group (AHG): injected with human insulin (humulin)
intraperitoneal (ip) in a dose of 10 U/kg, food was then withheld for 6 hours. (3)
Recurrent insulin-induced hypoglycemia group (RHG): received recurrent ip
injection with 10 U/kg humulin once per day for three consecutive days, food is given
after 2 hours and in the fourth day they received the same dose of insulin, then food
was withheld for 6 hours. Blood glucose was measured before and 30, 60, 90 and 120
min after the injection. Plasma levels of CK, LDH were estimated before and 6 hours
after the injection. Epinephrine levels were measured before and 90 min after the
injection. Animals were sacrificed by decapitation 6 h after the injection for
measurement of malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in
skeletal muscle and heart tissue homogenate. Results: it was found that acute and
recurrent insulin induced hypoglycemia caused elevated levels of plasma CK, LDH,
increase lipid peroxidations (MDA) together with decrease in T-AOC in skeletal
muscle and heart tissue homogenate. The plasma epinephrine levels in response to
hypoglycemia were significantly more in AHG group and RHG group at day 1 than
control. It was also demonstrated that recurrent insulin induced hypoglycemia
resulted in more increase in the levels of plasma CK, LDH and MDA with more
decrease in T-AOC and blood glucose levels compared to acute insulin hypoglycemia
rats. There was also revealed lower epinephrine levels in response to recurrent
hypoglycemia at day 4 compared to control.
Conclusions: our findings indicate that acute and recurrent insulin induced
hypoglycemia caused skeletal muscle and heart damage. This damage may be
attributed to increased oxidative stress revealed in those tissues. This damaging effect  is more following recurrent hypoglycemia which may be related to the lower
epinephrine levels in response to recurrent hypoglycemia detected in this group. That
resulted in more decrease in blood glucose and therefore more damaging effects to
those tissues.