Islet amyloid polypeptide in pancreatic islets from type 1 diabetic subjects

Abstract

Key words: immunocytochemistry, islet amyloid polypeptide, pancreatic islets, type 1 diabetes injection compliments insulin treatment to have a better glycemic control through suppressing glucagon secretion. This study was aimed to investigate the possible IAPP deficient pancreatic islets being responsible for severe IAPP hyposecretion in type 1 diabetics. Results Control islets.Large control islets consisted of major insulin cells, followed by glucagon and SRIF cells at a relative ratio of 6:3:1 whereas in medium sized islets, the relative ratio of three kinds of islet cells was 6:3:1.5 (Table 1 and Fig. 1). About 34% of islet cells were positively stained for IAPP and the ratio of IAPP positive cells to insulin cells was about 60% corresponding to the darkly insulin positive cells (Fig. 1). There were scattered, irregular, sickle-shaped cytoplasms often without nucleus, which were densely positive for both insulin and IAPP without granular appearance (Fig. 1A and B). Insulin ©2 0 1 1 L a n d e s B i o s c i e n c e . D o n o t d i s t r i b u t e .www.landesbioscience.com Islets

Apoptosis of pancreatic β-cells in type 1 diabetes: The role of Caspase-3 in β-cell apoptosis

“…The pancreas was obtained at autopsy from T1D subjects of ages 18 to 75, and the immunocytochemical presence of ACC suggests that ACC mediated apoptosis was in the ongoing process even at the subjects' death with a delicate balance of β-cell apoptosis and regeneration. These data also support that β-cell apoptosis and regeneration process is progressive from the preclinical stage to the end-stage of T1D and T2D 40,41 . The ACC positive β-islet cells were more in type 1 diabetic islets than in type 2 diabetic islets [39][40][41] .…”

“…These data also support that β-cell apoptosis and regeneration process is progressive from the preclinical stage to the end-stage of T1D and T2D 40,41 . The ACC positive β-islet cells were more in type 1 diabetic islets than in type 2 diabetic islets [39][40][41] .…”

“…Our data on ACC-positive cells were 15.7 % for type 1 diabetic islets 43 . Observing immunofluorescence photomicrographs, the positive staining was not clear and hazy for both ACC immunostaining and TUNEL including positive staining in the perinuclear cytoplasm 42 , not as clear as our ACC immunoperoxidase staining 39,41 . Another study using TUNEL reported 0.5% positive cells for normal β-cells 43 .…”

“…One type of large islets consists exclusively of α-cells and PP-cells (50% each) with practically no remaining β-cells and less ACC-cells, suggesting that these large islets correspond to the burntout, end-stage apoptosis-completed stage in response to long-stand compensation of insulin secretion ( Figure 4.E-H) (Case 8) 39 . Another type of large islets consists of remaining weakly insulin-staining minor β-cells, major α-cells and relatively decreased islet amyloid polypeptide (IAPP)-positive β-cells (16%), which represent remaining β-cells with less insulin and lesser IAPP immunostaining, thus suggesting apoptotic β-cell containing less insulin and even lesser IAPP, (Case 7, Table 2) (Figure 4A-D) 41 . The extra-large islets from Case 7 in Table 2 revealed weakly insulin-positive granular β-cells containing abundant cytoplasm with lesser IAPP-positive cells (17%), major α-cells (39%) and increased δ-cells (28%) plus irregular sickle-shaped densely IAPP-positive β-cells ( Figure 4E-H) 41 .…”

“…Another type of large islets consists of remaining weakly insulin-staining minor β-cells, major α-cells and relatively decreased islet amyloid polypeptide (IAPP)-positive β-cells (16%), which represent remaining β-cells with less insulin and lesser IAPP immunostaining, thus suggesting apoptotic β-cell containing less insulin and even lesser IAPP, (Case 7, Table 2) (Figure 4A-D) 41 . The extra-large islets from Case 7 in Table 2 revealed weakly insulin-positive granular β-cells containing abundant cytoplasm with lesser IAPP-positive cells (17%), major α-cells (39%) and increased δ-cells (28%) plus irregular sickle-shaped densely IAPP-positive β-cells ( Figure 4E-H) 41 . The pancreas was obtained at autopsy from T1D subjects of ages 18 to 75, and the immunocytochemical presence of ACC suggests that ACC mediated apoptosis was in the ongoing process even at the subjects' death with a delicate balance of β-cell apoptosis and regeneration.…”