Characterization of the endocrine pancreas in Type 1 Diabetes: islet size is maintained but islet number is markedly reduced
| Autor: | Olle Korsgren, Knut Dahl-Jørgensen, Oskar Skog, Anna Wiberg, Frode L. Jahnsen, Peter Seiron, Lars Krogvold |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
endocrine system
0303 health sciences medicine.medical_specialty geography Type 1 diabetes geography.geographical_feature_category endocrine system diseases Insulin medicine.medical_treatment Pancreatic islets 030209 endocrinology & metabolism Biology Islet medicine.disease 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Endocrinology Internal medicine medicine PDX1 Endocrine system Pancreas Beta (finance) 030304 developmental biology |
| DOI: | 10.1101/480509 |
| Popis: | Insulin deficiency in type 1 diabetes (T1D) is generally considered a consequence of specific beta-cell loss. Since healthy pancreatic islets consist of ~65% beta cells, this would lead to reduced islet size if the beta cells are not replaced by other cells or tissue. The number of islets per pancreas volume (islet density) would not be affected.In this study, we compared the islet density, size, and size distribution in subjects with recent-onset or long-standing T1D, with that in matched non-diabetic subjects. Results show that subjects with T1D, regardless of disease duration, had a dramatically reduced islet number per mm2, while the islet size was similar in all groups. Insulin-negative islets in T1D subjects were dominated by glucagon-positive cells that frequently had lost the alpha-cell transcription factor ARX while instead expressing PDX1, normally expressed in beta cells.Based on our findings, we propose that failure during childhood to establish a sufficient islet number to reach the beta-cell mass needed to cope with episodes of increased insulin demand contributes to T1D susceptibility. Exhaustion induced by relative lack of beta cells could then potentially drive beta-cell dedifferentiation to alpha-cells, explaining the preserved islet size observed in T1D compared to controls. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|