Role of insulin signaling in maintaining energy homeostasis.
OBJECTIVE
To examine the role that insulin signaling plays in modulating metabolic functions involving both peripheral and hypothalamic systems.


METHODS
We review the literature regarding insulin signaling as it relates to energy homeostasis.


RESULTS
Insulin signaling in the periphery is known to affect hepatic glucose production and glucose uptake in muscle and adipose tissue. In the brain, insulin is involved in a variety of signaling pathways that control positive and negative aspects of food intake and energy metabolism. Disruption of insulin signaling can affect key cellular pathways that serve to maintain energy balance and glucose homeostasis, which can then lead to insulin resistance and progression toward various metabolic disorders, including cardiovascular disease, obesity, and type 2 diabetes. The use of exogenous insulin as therapy for patients with type 2 diabetes is traditionally associated with increases in weight.


CONCLUSIONS
An enhanced understanding of how these insulin signaling pathways function may provide answers about how to control weight gain associated with exogenous insulin use. Pharmacologic agents, such as the long-acting insulin analogues and particularly insulin detemir, that may reduce these weight effects hold considerable advantage.
Sharma
Morali D
MD
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine, Houston, Texas 77030, USA.
Garber
Alan J
AJ
Farmer
John A
JA
D000818:Animals; D001921:Brain / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives / Q000502:physiology* / Q000627:therapeutic use; D008099:Liver / Q000502:physiology; D009765:Obesity / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin