Type 2 diabetes is well recognized as a noninsulin-dependent diabetic disease. Clinical evidence indicates that the level of circulating
insulin may be normal, subnormal, and even elevated in type 2 diabetic patients. Unlike
type 1 diabetes, the key problem for
type 2 diabetes is not due to the absolute deficiency of insulin secretion, but because the body is no longer sensitive to
insulin. Thus,
insulin resistance is increased and the sensitivity to
insulin is reset, so increasing levels of
insulin are required to maintain body
glucose and metabolic homeostasis. How
insulin resistance is increased and what factors contribute to its development in
type 2 diabetes remain incompletely understood. Overemphasis of
insulin deficiency alone may be too simplistic for us to understand how
type 2 diabetes is developed and should be treated, since
glucose metabolism and homeostasis are tightly controlled by both
insulin and
glucagon.
Insulin acts as a YIN factor to lower
blood glucose level by increasing cellular
glucose uptake, whereas
glucagon acts as a YANG factor to counter the action of
insulin by increasing
glucose production. Furthermore, other humoral factors other than
insulin and
glucagon may also directly or indirectly contribute to increased
insulin resistance and the development of
hyperglycemia. The purpose of this article is to briefly review recently published animal and human studies in this field, and provide new insights and perspectives on recent debates as to whether hyperglucagonemia and/or
glucagon receptors should be targeted to treat
insulin resistance and target organ injury in
type 2 diabetes.