Diabetes mellitus (DM) is a major p

Diabetes mellitus (DM) is a major public health problem worldwide.
It is characterized by hyperglycemia resulting from defi-
ciencies in insulin secretion and/or insulin action. Type 2 DM
is the most common form of diabetes, accounting for above
90% of patients with diabetes. Insulin resistance, a key factor
in the pathogenesis of obesity and Type 2 diabetes, is a pathological
state in which target cells fail to respond to a normal
level of circulating insulin (Kaidanovich & Eldar-Finkelman,
2002).
The primary biological effect of insulin is the maintenance
of whole-body glucose homeostasis. Under normal conditions,
insulin binds to insulin receptors and evokes insulin
signal transduction cascades, which mediate the regulation
of glucose metabolism and glucose transport as well as the
promotion of glycogen synthesis (Zick, 2001). The stimulus
of insulin may increase the expression of glucokinase (GK)
(Saltiel & Kahn, 2001), which promotes glucose utilization
and glycogen deposition in the liver (Ferrer et al., 2003).
Insulin also inhibits glycogen synthase kinase-3 (GSK-3) and
thus further promotes dephosphorylation and activation of
glycogen synthase (GS), which is crucial for the catalysis of
glycogen synthesis (Bouskila, Hirshman, Jensen, Goodyear,
& Sakamoto, 2008). In addition, insulin can reduce glucose
production by inhibiting hepatic nuclear factor-4 (HNF-4)
and phosphoenolpyruvate carboxykinase (PEPCK) activities,
thus maintaining glucose homeostasis (Saltiel & Kahn, 2001)