Energy-dependent modulation of glucagon-like signaling in Drosophila via the AMP-activated protein kinase.
Adipokinetic hormone (AKH) is the equivalent of mammalian glucagon, as it is the primary insect hormone that causes energy mobilization. In Drosophila, current knowledge of the mechanisms regulating AKH signaling is limited. Here, we report that AMP-activated protein kinase (AMPK) is critical for normal AKH secretion during periods of metabolic challenges. Reduction of AMPK in AKH cells causes a suite of behavioral and physiological phenotypes resembling AKH cell ablations. Specifically, reduced AMPK function increases life span during starvation and delays starvation-induced hyperactivity. Neither AKH cell survival nor gene expression is significantly impacted by reduced AMPK function. AKH immunolabeling was significantly higher in animals with reduced AMPK function; this result is paralleled by genetic inhibition of synaptic release, suggesting that AMPK promotes AKH secretion. We observed reduced secretion in AKH cells bearing AMPK mutations employing a specific secretion reporter, confirming that AMPK functions in AKH secretion. Live-cell imaging of wild-type AKH neuroendocrine cells shows heightened excitability under reduced sugar levels, and this response was delayed and reduced in AMPK-deficient backgrounds. Furthermore, AMPK activation in AKH cells increases intracellular calcium levels in constant high sugar levels, suggesting that the underlying mechanism of AMPK action is modification of ionic currents. These results demonstrate that AMPK signaling is a critical feature that regulates AKH secretion, and, ultimately, metabolic homeostasis. The significance of these findings is that AMPK is important in the regulation of glucagon signaling, suggesting that the organization of metabolic networks is highly conserved and that AMPK plays a prominent role in these networks.
Department of Biology, Wake Forest University, Winston-Salem, NC 27109, USA.
Jason T
JT
Braco
Emily L
EL
Gillespie
Gregory E
GE
Alberto
Jay E
JE
Brenman
Erik C
EC
Johnson
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002470:Cell Survival; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D007301:Insect Hormones / Q000235:genetics / Q000378:metabolism; D055099:Neuroendocrine Cells / Q000378:metabolism; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives*; D015398:Signal Transduction
D007301:Insect Hormones; D009842:Oligopeptides; C044833:adipokinetic hormone; D005934:Glucagon; D055372:AMP-Activated Protein Kinases; D011761:Pyrrolidonecarboxylic Acid