Hid-1 Is A Novel Player In The Regulation Of Blood Glucose

Peptide hormones and neuropeptides are packaged and stored in specialized intracellular organelles called secretory granules (SGs, also known as dense core vesicles, DCVs). The molecular mechanisms involved in SG biogenesis from the trans-Golgi network (TGN) are largely unknown. A gene designated as hid-1 was identified during a search for mutants with a high-temperature-induced dauer formation (Hid) phenotype in C. elegans. Hid-1 is highly conserved from C. elegans to Homo sapiens. Interestingly, the Hid phenotype of hid-1 mutants is strongly suppressed in C. elegans by mutations in the daf-16 gene, which encodes for a transcription factor downstream of insulin signaling, suggesting a possible role for HID-1 in the insulin branch of the dauer pathway. Our recent studies in C. elegans have implicated an involvement of HID-1 in the early steps of SG exocytosis by controlling the correct sorting of SG cargoes. We demonstrated that HID-1 primarily localized to the medial- and trans-Golgi apparatus. We furthered our study of HID-1 functions in a pancreatic beta cell-specific HID-1 knockout mouse model. We found that HID-1 participated in the regulation of blood glucose. HID-1 deficiency in β cells leads to insufficient insulin release. The molecular mechanism of HID-1 is under investigation.