| 1. |
- Coppieters, Ken T., et al.
(författare)
-
Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals
- 2011
-
Ingår i: Diabetes/Metabolism Research Reviews. - : Wiley. - 1520-7552 .- 1520-7560. ; 27:8, s. 746-754
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent reports have established the notion that many patients with longstanding type 1 diabetes (T1D) possess a remnant population of insulin-producing beta cells. It remains questionable, however, whether these surviving cells can physiologically sense and respond to glucose stimuli.METHODS: Frozen pancreatic sections from non-diabetic donors (n=8), type 2 diabetic patients (n=4), islet autoantibody-positive non-diabetic patients (n=3), type 1 diabetic patients (n=10) and one case of gestational diabetes were obtained via the network for Pancreatic Organ Donors. All longstanding T1D samples were selected based on the detection of insulin-producing beta cells in the pancreas by immunohistochemistry. RNA was isolated from all sections followed by cDNA preparation and quantitative real-time polymerase chain reaction for insulin, glucose transporter 1 (GLUT1), GLUT2 and GLUT3. Finally, immunofluorescent staining was performed on consecutive sections for all four of these markers and a comparison was made between the expression of GLUT2 in humans versus NOD mice.RESULTS: In contrast to islets from the most widely used T1D model, the NOD mouse, human islets predominantly express GLUT1 and, to a much lesser extent, GLUT3 on their surface instead of GLUT2. Relative expression levels of these receptors do not significantly change in the context of the various (pre-)diabetic conditions studied. Moreover, in both species preservation of GLUT expression was observed even under conditions of substantial leucocyte infiltration or decades of T1D duration.CONCLUSIONS: These data suggest that despite being subjected to multiple years of physiological stress, the remaining beta-cell population in longstanding T1D patients retains a capacity to sense glucose via its GLUTs.
|
|
| 2. |
- Rodriguez-Calvo, Teresa, et al.
(författare)
-
Increased immune cell infiltration of the exocrine pancreas: a possible contribution to the pathogenesis of type 1 diabetes.
- 2014
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 63:11, s. 3880-90
-
Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) results from a complex interplay between genetic susceptibility and environmental factors that have been implicated in the pathogenesis of disease both as triggers and potentiators of β-cell destruction. CD8 T cells are the main cell type found in human islets, and they have been shown in vitro to be capable of killing β-cells overexpressing MHC class I. In this study, we report that CD8 T cells infiltrate the exocrine pancreas of diabetic subjects in high numbers and not only endocrine areas. T1D subjects present significantly higher CD8 T cell density in the exocrine tissue without the presence of prominent insulitis. Even T1D donors without remaining insulin-containing islets and long disease duration show elevated levels of CD8 T cells in the exocrine compartment. In addition, higher numbers of CD4(+) and CD11c(+) cells were found in the exocrine tissue. Preliminary data in type 2 diabetic (T2D) subjects indicate that overall, there might be a spontaneous inflammatory infiltration of the exocrine tissue, common to both T1D and T2D subjects. Our study provides the first information on the precise tissue distribution of CD8 T cells in pancreata from T1D, T2D, autoantibody-positive, and healthy control subjects.
|
|
