title: Regulation of glucagon secretion by zinc: lessons from the β cell-specific Znt8 knockout mouse model.
abstract: In type-2 diabetes, hyperglucagonaemia aggravates elevated blood glucose levels. Relative to our knowledge of the β-cell and insulin secretion, there remains a limited understanding of glucagon secretion in α-cells. Regulation of glucagon may be dependent on a combination of factors, which include direct glucose sensing by the α-cell, innervations from the autonomic nervous system and potential 'paracrine' actions by hormones and factors that are released by adjacent endocrine cells within the islets. The list of potential 'paracrine' regulators within the islet includes insulin, somatostatin, γ-aminobutyric acid, glutamate and zinc. Zinc crystallises with insulin in β-cells and is co-secreted with insulin. In the scientific literature, the effect of exogeneous zinc on glucagon secretion has been debated. Here, we confirm that an increase in exogeneous zinc does inhibit glucagon secretion. To determine if there are physiological effects of zinc on glucagon secretion we used a β-cell-specific ZnT8 knockout (Znt8BKO) mouse model. Znt8BKO mice, despite showing lower granular zinc content in β-cells, showed no changes in fasted plasma glucagon levels and glucose regulated glucagon secretion. These findings suggest that zinc secreted from β-cell does not regulate glucagon secretion.
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
authors.forename: A B
authors.initials: AB
authors.lastname: Hardy
authors.forename: A S
authors.initials: AS
authors.lastname: Serino
authors.forename: N
authors.initials: N
authors.lastname: Wijesekara
authors.forename: F
authors.initials: F
authors.lastname: Chimienti
authors.forename: M B
authors.initials: MB
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015032:Zinc / Q000378:metabolism*; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; D007328:Insulin; C516348:Slc30a8 protein, mouse; D000075703:Zinc Transporter 8; D005934:Glucagon; D015032:Zinc