Function of Isolated Pancreatic Islets From Patients at Onset of Type 1 Diabetes: Insulin Secretion Can Be Restored After Some Days in a Nondiabetogenic Environment In Vitro

Author:

Krogvold Lars1,Skog Oskar2,Sundström Görel3,Edwin Bjørn4,Buanes Trond5,Hanssen Kristian F.6,Ludvigsson Johnny7,Grabherr Manfred3,Korsgren Olle2,Dahl-Jørgensen Knut1

Affiliation:

1. Paediatric Department, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway

2. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

3. Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden

4. Intervention Centre and Department of Surgery, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway

5. Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway

6. Department of Endocrinology, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway

7. Division of Paediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

Abstract

The understanding of the etiology of type 1 diabetes (T1D) remains limited. One objective of the Diabetes Virus Detection (DiViD) study was to collect pancreatic tissue from living subjects shortly after the diagnosis of T1D. Here we report the insulin secretion ability by in vitro glucose perifusion and explore the expression of insulin pathway genes in isolated islets of Langerhans from these patients. Whole-genome RNA sequencing was performed on islets from six DiViD study patients and two organ donors who died at the onset of T1D, and the findings were compared with those from three nondiabetic organ donors. All human transcripts involved in the insulin pathway were present in the islets at the onset of T1D. Glucose-induced insulin secretion was present in some patients at the onset of T1D, and a perfectly normalized biphasic insulin release was obtained after some days in a nondiabetogenic environment in vitro. This indicates that the potential for endogenous insulin production is good, which could be taken advantage of if the disease process was reversed at diagnosis.

Funder

EXODIAB

Juvenile Diabetes Research Foundation, Sweden

RFI/VR “SNISS” Swedish National Infrastructure for large Scale Sequencing

Science for Life Laboratory, Uppsala, Sweden

Swedish Medical Research Council

Barndiabetesfonden

Diabetes Wellness Sweden

Family Ernfors Fund

Swedish Diabetes Foundation

Swedish National Institutes of Health

South-Eastern Norway Regional Health Authority

PEVNET Study Group

Novo Nordisk Foundation

EXODIAB (Excellence of Diabetes Research in Sweden)

Barndiabetesfonden (Swedish Child Diabetes Foundation)

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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