title: Glucose control of glucagon secretion-'There's a brand-new gimmick every year'.
abstract: Glucagon from the pancreatic α-cells is a major blood glucose-regulating hormone whose most important role is to prevent hypoglycaemia that can be life-threatening due to the brain's strong dependence on glucose as energy source. Lack of blood glucose-lowering insulin after malfunction or autoimmune destruction of the pancreatic β-cells is the recognized cause of diabetes, but recent evidence indicates that diabetic hyperglycaemia would not develop unless lack of insulin was accompanied by hypersecretion of glucagon. Glucagon release has therefore become an increasingly important target in diabetes management. Despite decades of research, an understanding of how glucagon secretion is regulated remains elusive, and fundamentally different mechanisms continue to be proposed. The autonomous nervous system is an important determinant of glucagon release, but it is clear that secretion is also directly regulated within the pancreatic islets. The present review focuses on pancreatic islet mechanisms involved in glucose regulation of glucagon release. It will be argued that α-cell-intrinsic processes are most important for regulation of glucagon release during recovery from hypoglycaemia and that paracrine inhibition by somatostatin from the δ-cells shapes pulsatile glucagon release in hyperglycaemia. The electrically coupled β-cells ultimately determine islet hormone pulsatility by releasing synchronizing factors that affect the α- and δ-cells.
authors.affiliation: a Department of Medical Cell Biology , Uppsala University , Uppsala , Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Gylfe
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000166:cytology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology*; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D013004:Somatostatin / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D005947:Glucose
keywords: Diabetes; glucagon secretion; glucose homeostasis; signal transduction