THE ARCUATE K ATP CHANNEL IN HEALTH, OBESITY AND DIABETE

Project Details

Description

This proposal examines the effects of diet-induced obesity (DIO) and non-insulin dependent diabetes mellitus (NIDDM) on the ATP-sensitive K+ (K-ATP) channel located on neurons in the arcuate nucleus (ARC) which integrate metabolic signals concerning energy balance. The overall objective is to investigate the mechanisms by which arcuate glucosensing neurons sense and respond to changes in glucose homeostasis. To achieve this objective the following two hypotheses will be tested using a rodent model of DIO and NIDDM. HYPOTHESIS I is that the K-ATP channel regulates the generation of action potentials on ARC neurons by responding to changes in intracellular ATP. This hypothesis derives from our knowledge of the pancreatic beta-cell in which ATP is a critical regulator of K-ATP channel activity and insulin secretion. HYPOTHESIS II is that central and peripheral signals which regulate energy homeostasis will also regulate the ARC K-ATP channel via their effects on phosphorylation. These hypotheses will be tested using whole cell and single channel patch clamp recordings of ARC K-ATP channel currents in isolated cells as well as intact brain slices. These studies will provide new insights into the way in which the brain controls and is controlled by changes in glucose metabolism in obesity and diabetes.
StatusFinished
Effective start/end date2/1/006/30/11

Funding

  • National Institutes of Health: $206,027.00
  • National Institutes of Health: $390,000.00
  • National Institutes of Health: $296,212.00
  • National Institutes of Health: $302,258.00
  • National Institutes of Health: $289,064.00
  • National Institutes of Health: $280,092.00
  • National Institutes of Health: $216,541.00
  • National Institutes of Health: $211,208.00
  • National Institutes of Health: $200,998.00
  • National Institutes of Health: $237,148.00

ASJC

  • Medicine(all)

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