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

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.

Expression of Interferon-Stimulated Genes in Insulitic Pancreatic Islets of Patients Recently Diagnosed With Type 1 Diabetes

“…The DiViD samples were collected by pancreatic tail resections performed 3-9 weeks after the diagnosis of T1D, and the patient characteristics have been described previously in detail (18)(19)(20)(21). Goodquality RNA, suitable for use in this present study, was possible to extract from laser-captured islets from DiViD cases 2-6.…”

“…Total RNA extracted from islets isolated by collagenase digestion from the tip of the tail was subjected to whole transcriptome sequencing as reported (20). Normalized reads per kilobase per million mapped reads for the genes included in the RT2 Profiler PCR array for ISGs are presented in this study, and the full data set (reads) is openly available in the BILS DOI repository (http://doi.bils.se/) under DOI number 10.17044/BILS/G000002.…”

Children diagnosed with both Type 1 diabetes and Celiac disease - An Immunological challenge

“…In this rare in vivo study of human pancreas, mean glucose-stimulated insulin secretion was reduced in islets from T1D patients [52] . Also the genes involved in production and release of insulin as well as genes involved in secretion of insulin for example the insulin gene INS were less expressed in patients than in controls [52] .…”

Presumptive Type 1 Diabetes With Comorbidities and Rapid Progression Despite Numerous Insulin-Positive Islets

“…We wondered why this patient had such severe comorbidities, presumed rapid disease progression, and early death despite the presence of insulin-positive b-cells, appreciable C-peptide, and HLA associated with protection against type 1 diabetes. Perhaps these observations were solely due to poor glycemic control; alternatively, peripheral insulin resistance (11) and/or b-cell dysfunction (related to impaired blood glucose sensing, signal transduction, insulin processing, or insulin secretion) (12) might have been at play.…”