UMMS Affiliation

Department of Medicine, Diabetes Center of Excellence

Publication Date

2019-01-02

Document Type

Article

Disciplines

Endocrine System Diseases | Endocrinology | Endocrinology, Diabetes, and Metabolism | Hormones, Hormone Substitutes, and Hormone Antagonists | Nutritional and Metabolic Diseases

Abstract

Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found that donor islets contained beta cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in the gene encoding hepatocyte nuclear factor-1alpha (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment.

Keywords

Diabetes, Endocrinology, Insulin, Islet cells

Rights and Permissions

Copyright © 2019, American Society for Clinical Investigation. Publisher PDF posted as allowed by publisher's policy posted at https://www.jci.org/kiosks/terms.

DOI of Published Version

10.1172/JCI121994

Source

J Clin Invest. 2019 Jan 2;129(1):246-251. doi: 10.1172/JCI121994. Epub 2018 Dec 3. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of clinical investigation

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

30507613

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