American Diabetes Association
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Effects of GLP-1 and GIP on islet function in glucose intolerant, pancreatic insufficient cystic fibrosis

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posted on 2022-07-07, 13:43 authored by 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


Impaired insulin and incretin secretion underlie abnormal glucose tolerance (AGT) in pancreatic insufficient cystic fibrosis (PI-CF). Whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can enhance pancreatic islet function in 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 by randomized, double-blind, cross-over fashion. Another 4 adults with PI-CF and normal glucose tolerance (NGT) and 4 matched non-CF controls 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 non-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 benefit in this population.  Understanding loss of GIP’s insulinotropic action in PI-CF may lead to novel insights into diabetes pathogenesis. 


This study was supported by Public Health Service research grants R01 DK97830 (to AK and MRR), K23 DK107937 (to SS), UL1 TR001878 (University of Pennsylvania Center for Human Phenomic Science), P30 DK19525 (University of Pennsylvania Diabetes Research Center), and T32 DK007314 (University of Pennsylvania Training Grant in Diabetes, Endocrine and Metabolic Diseases) from the National Institutes of Health, Cystic Fibrosis Foundation grant RICKEL19A0-I (to MRR and AK), and the Human Metabolism Resource of the University of Pennsylvania Institute for Diabetes, Obesity & Metabolism


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