Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis

Sarah C. Nyirjesy, Amy J. Peleckis, Jack N. Eiel, Kathryn Gallagher, Andriana Doliba, Abigail Tami, Anneliese J. Flatt, Diva D. De Leon, Denis Hadjiliadis, Saba Sheikh, Darko Stefanovski, Robert Gallop, David A. D’alessio, Ronald C. Rubenstein, Andrea Kelly, Michael R. Rickels

Research output: Contribution to journalArticlepeer-review

Abstract

Impaired insulin and incretin secretion underlie abnormal glucose tolerance (AGT) in pancreatic insufficient cystic fibrosis (PI-CF). Whether the incretin hormones glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can enhance pancreatic islet function in cystic fibrosis (CF) is not known. We studied 32 adults with PI-CF and AGT randomized to receive either GLP-1 (n = 16) or GIP (n = 16) during glucose-potentiated arginine (GPA) testing of islet function on two occasions, with either incretin or placebo infused, in a randomized, double-blind, cross-over fashion. Another four adults with PI-CF and normal glucose tolerance (NGT) and four matched control participants without CF underwent similar assessment with GIP. In PI-CF with AGT, GLP-1 substantially augmented second-phase insulin secretion but without effect on the acute insulin response to GPA or the proinsulin secretory ratio (PISR), while GIP infusion did not enhance second-phase or GPA-induced insulin secretion but increased the PISR. GIP also did not enhance second-phase insulin in PI-CF with NGT but did so markedly in control participants without CF controls. These data indicate that GLP-1, but not GIP, augments glucose-dependent insulin secretion in PI-CF, supporting the likelihood that GLP-1 agonists could have therapeutic benefitinthis population. Understanding loss of GIP’s insulinotropic action in PI-CF may lead to novel insights into diabetes pathogenesis.

Original languageEnglish
Pages (from-to)2153-2165
Number of pages13
JournalDiabetes
Volume71
Issue number10
DOIs
StatePublished - Oct 2022

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