Islet Function in the Pathogenesis of Cystic Fibrosis-Related Diabetes Mellitus

Author:

Westholm Efraim1ORCID,Wendt Anna1ORCID,Eliasson Lena1ORCID

Affiliation:

1. Department of Clinical Sciences in Malmö, Islet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Malmö, Sweden

Abstract

Cystic fibrosis-related diabetes mellitus (CFRD) is the most common non-pulmonary co-morbidity in cystic fibrosis (CF). CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene ( CFTR), which leads to aberrant luminal fluid secretions in organs such as the lungs and pancreas. How dysfunctional CFTR leads to CFRD is still under debate. Both intrinsic effects of dysfunctional CFTR in hormone secreting cells of the islets and effects of exocrine damage have been proposed. In the current review, we discuss these non-mutually exclusive hypotheses with a special focus on how dysfunctional CFTR in endocrine cells may contribute to an altered glucose homeostasis. We outline the proposed role of CFTR in the molecular pathways of β-cell insulin secretion and α-cell glucagon secretion, and touch upon the importance of the exocrine pancreas and intra-pancreatic crosstalk for proper islet function.

Funder

CF-Trust

the Swedish Foundation for Strategic Research

the Swedish Research Council

Region Skåne-ALF

The Swedish Diabetes Foundation and Albert Påhlsson Foundation

Publisher

SAGE Publications

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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