Zebrafish as models of mammalian glucagon action

Glucagon is produced by the α-cells in the pancreas and, acting via its receptor (GCGR), it regulates hepatic glucose production. Glucagon antagonism results in hypoglycaemia and can protect against the development of diabetes mellitus, and so it is seen as a potential treatment. However, it is associated with α-cell hyperplasia and tumour growth, the molecular mechanisms for which are unidentified. If you work on human disease, you are probably wary of animal models and may have never gone near a zebrafish, but read on… Li et al. identified two functional (accumulation of cAMP following stimulation) GCGRs in zebrafish. Knockout of these GCGRs in zebrafish larvae results in lower glucose and higher glucagon levels and α-cell hyperplasia. This demonstrates that the compensatory mechanism to glucagon deficiency or interruption of glucagon signalling is conserved in zebrafish, and that GCGR-deficient zebrafish offer an opportunity to unravel the signals that regulate α-cell mass. Read the full article in Journal of Endocrinology 227 93–103