title: Interleukin-1 signaling contributes to acute islet compensation.
abstract: IL-1β is a well-established inducer of both insulin resistance and impaired pancreatic islet function. Despite this, findings examining IL-1 receptor deficiency or antagonism in in vivo animal models, as well as in clinical studies of type 2 diabetic (T2D) patients, have led to conflicting results, suggesting that the actions of IL-1β on glycemic control may be pleiotropic in nature. In the present work, we find that the ability of IL-1β to amplify glucose-stimulated insulin secretion from human islets correlates with donor BMI. Islets from obese donors are sensitized to the insulinotropic effects of this cytokine, whereas the stimulatory effects of IL-1β are lost in islets from obese T2D patients, suggesting a role for IL-1 signaling in islet compensation. Indeed, mice deficient in IL-1 receptor type I become glucose intolerant more rapidly than their WT littermates and have impaired secretory responses during the acute stages of inflammatory and metabolic stress induced by LPS and high-fat diet, respectively. IL-1β directly enhances β cell insulin secretion by increasing granule docking and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex formation at the plasma membrane. Together, our study highlights the importance of IL-1β signaling in islet compensation to metabolic and inflammatory stress.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hajmrle
authors.forename: Nancy
authors.initials: N
authors.lastname: Smith
authors.forename: Aliya F
authors.initials: AF
authors.lastname: Spigelman
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Dai
authors.forename: Laura
authors.initials: L
authors.lastname: Senior
authors.forename: Austin
authors.initials: A
authors.lastname: Bautista
authors.forename: Mourad
authors.initials: M
authors.lastname: Ferdaoussi
authors.forename: Patrick E
authors.initials: PE
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D053583:Interleukin-1beta / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged
chemical_list: C508585:IL1B protein, human; D007328:Insulin; D053583:Interleukin-1beta