Calmodulin Kinases and Control of Skeletal Muscle Glucose Metabolism Grant uri icon

abstract

  • Type 2 diabetes costs the U.S. healthcare system over $245 billion/year. It is a disease defined by hyperglycemia, hyperinsulinemia and defects in insulin-stimulated glucose uptake into skeletal muscle. Despite the importance of skeletal muscle in maintaining systemic glucose homeostasis, there are currently no pharmaceutical treatments for type 2 diabetes that target muscle glucose uptake independent of insulin. Thus, the long-term goal of this research is to identify cellular or molecular mechanisms that stimulate muscle glucose uptake independent of insulin and to target those mechanisms for new type 2 diabetes treatments. Excitingly, we have discovered that in mouse skeletal muscle expression of a constitutively active form of the Ca2+/calmodulin-dependent protein kinase kinase alpha (CaMKKalpha) increases glucose uptake additively with insulin (~4-fold), in insulin-resistant muscle (~2-fold), and independent of insulin signaling proteins; suggesting that CaMKKalpha may be a new target for treating type 2 diabetes. Unfortunately, the mechanism(s) underlying CaMKKalpha-induced glucose uptake are currently unknown. Thus, the objective of this proposal is to identify the signaling proteins, metabolic and/or biosynthetic pathways that are stimulated in response to active CaMKKalpha signaling in muscle.

date/time interval

  • July 2015 - April 2020