Glucokinase (GK) plays a critical role in the control of whole-body
glucose homeostasis. We investigated the possible effects of a novel
glucokinase activator (GKA),
HMS5552, to the GK in rats with
type 2 diabetes mellitus (T2DM). Male Sprague-Dawley (SD) rats were divided into four groups: control group, diabetic group, low-dose (10 mg/kg) HMS5552-treated diabetic group (HMS-L), and high-dose (30 mg/kg) HMS5552-treated diabetic group (HMS-H).
HMS5552 was administered intragastrically to the T2DM rats for one month. The levels of total
cholesterol,
triglyceride, fasting plasma
insulin (FINS), and
glucagon (FG) were determined, and an oral
glucose tolerance test was performed. The expression patterns of
proteins and genes associated with
insulin resistance and GK activity were assayed. Compared with diabetic rats, the FINS level was significantly decreased in the HMS5552-treated diabetic rats.
HMS5552 treatment significantly lowered the
blood glucose levels and improved GK activity and
insulin resistance. The immunohistochemistry, western blot, and semiquantitative RT-PCR results further demonstrated the effects of
HMS5552 on the liver and pancreas. Our data suggest that the novel GKA,
HMS5552, exerts
antidiabetic effects on the liver and pancreas by improving GK activity and
insulin resistance, which holds promise as a novel drug for the treatment of T2DM patients.