Both types of diabetes are characterized by progressive beta-cell failure and death, leading to absolute or relative insulin deficiency. To date, very limited information is available about the ultrastructural alterations of beta cells in human diabetes. We performed morphological and morphometric electron microscopy evaluation of pancreatic islet cells obtained from 5 non-diabetic (ND), 5 type 1 (T1D) and 5 type 2 (T2D) diabetic organ donors, with similar clinical features. The total number of islet cells examined was 954 in ND, 646 in T1D and 820 in T2D. A lower amount of beta cells was found in both T1D and T2D than in ND islets (57±3 and 47±4 vs. 69±2%, p<0.01), whereas no differences were observed for delta cells; alpha cells were increased (34.8±1.1 vs 24.8±1.8%, p<0.05) only in T2D. In both T1D and T2D more beta cells showed signs of apoptosis than in ND (6.8±2.0 and 9.3±2.3 vs. 2±1.3%, p<0.01). Insulin granules were less represented in T2D than in ND beta cells (3.1±0.5 vs. 8.7±1.1ml%, p<0.01), whereas no significant changes were found in T1D. Volume density of the endoplasmic reticulum was increased in T2D and unchanged in T1D samples (2.8±0.5, p<0.01, and 1.2±0.2 vs. 0.7±0.2 ml%); mitochondria number and volume (9.1±1.1 vs. 5.8±0.4 ml%) were also higher (both p<0.01) in T2D than in ND beta cells, whereas no significant differences were found in T1D. Finally, in the peri-insular infiltrate we found a higher number of macrophages (4.2±0.8 vs 1.0±0.2 cells/islet, p<0.01) in T2D and an increased number of mast cells (1.8±0.3 vs 0.5±0.2 cells/islet, p<0.01) in T1D. These results show that in each type of diabetes, beta cells have specific ultrastructural alterations, as cause or consequence of functional and survival defects; targeting the deranged organelles might improve the outcome of therapeutic interventions.
Ultrastructural Alterations of Beta Cells in Human Type 1 and Type 2 Diabetes Mellitus
MASINI, MATILDE;MARTINO, LUISA;MARSELLI, LORELLA;BUGLIANI, MARCO;MARCHETTI, PIERO;DE TATA, VINCENZO
2015-01-01
Abstract
Both types of diabetes are characterized by progressive beta-cell failure and death, leading to absolute or relative insulin deficiency. To date, very limited information is available about the ultrastructural alterations of beta cells in human diabetes. We performed morphological and morphometric electron microscopy evaluation of pancreatic islet cells obtained from 5 non-diabetic (ND), 5 type 1 (T1D) and 5 type 2 (T2D) diabetic organ donors, with similar clinical features. The total number of islet cells examined was 954 in ND, 646 in T1D and 820 in T2D. A lower amount of beta cells was found in both T1D and T2D than in ND islets (57±3 and 47±4 vs. 69±2%, p<0.01), whereas no differences were observed for delta cells; alpha cells were increased (34.8±1.1 vs 24.8±1.8%, p<0.05) only in T2D. In both T1D and T2D more beta cells showed signs of apoptosis than in ND (6.8±2.0 and 9.3±2.3 vs. 2±1.3%, p<0.01). Insulin granules were less represented in T2D than in ND beta cells (3.1±0.5 vs. 8.7±1.1ml%, p<0.01), whereas no significant changes were found in T1D. Volume density of the endoplasmic reticulum was increased in T2D and unchanged in T1D samples (2.8±0.5, p<0.01, and 1.2±0.2 vs. 0.7±0.2 ml%); mitochondria number and volume (9.1±1.1 vs. 5.8±0.4 ml%) were also higher (both p<0.01) in T2D than in ND beta cells, whereas no significant differences were found in T1D. Finally, in the peri-insular infiltrate we found a higher number of macrophages (4.2±0.8 vs 1.0±0.2 cells/islet, p<0.01) in T2D and an increased number of mast cells (1.8±0.3 vs 0.5±0.2 cells/islet, p<0.01) in T1D. These results show that in each type of diabetes, beta cells have specific ultrastructural alterations, as cause or consequence of functional and survival defects; targeting the deranged organelles might improve the outcome of therapeutic interventions.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
