Dataset Information

Temporal Analysis of Amylase Expression in Control, Autoantibody-Positive, and Type 1 Diabetes Pancreatic Tissues.

ABSTRACT: Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes and production of hormones to maintain metabolic homeostasis, respectively. While the vast majority of type 1 diabetes research efforts have focused on endocrine function and autoimmunity, recent studies identified a series of unique features (e.g., reduced weight and volume, increased density of leukocytes) within the exocrine pancreas in this disease, but the mechanisms underlying these aberrancies are unknown. Therefore, we histologically assessed amylase, insulin, glucagon, lipase, and/or trypsinogen in 78 organ donor pancreata from birth through adulthood in control subjects and those at various stages of type 1 diabetes. While amylase-positive (AMY⁺) acinar cells were detectable in pancreata from all study groups, tissues from individuals >2 years of age contained clusters of acinar cells devoid of amylase (AMY^-). A majority of these AMY^- cell clusters localized proximal to islets (i.e., peri-islet). Additionally, most AMY^- clusters were positive for the exocrine enzymes lipase and trypsinogen. Interestingly, type 1 diabetes pancreata displayed significant reductions in the frequency of these AMY^- cell clusters. These results support a contribution of the islet-acinar axis in pancreatic development and underscore a potential role for the exocrine pancreas in the pathogenesis of type 1 diabetes.

SUBMITTER: Kusmartseva I

PROVIDER: S-EPMC6925584 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Temporal Analysis of Amylase Expression in Control, Autoantibody-Positive, and Type 1 Diabetes Pancreatic Tissues.

Kusmartseva Irina I Beery Maria M Hiller Helmut H Padilla Myriam M Selman Stephen S Posgai Amanda A Nick Harry S HS Campbell-Thompson Martha M Schatz Desmond A DA Haller Michael J MJ Wasserfall Clive H CH Atkinson Mark A MA

Diabetes 20191009 1

Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes and production of hormones to maintain metabolic homeostasis, respectively. While the vast majority of type 1 diabetes research efforts have focused on endocrine function and autoimmunity, recent studies identified a series of unique features (e.g., reduced weight and volume, increased density of leukocytes) within the exocrine pancreas in this disease, but the mechanisms underlying these aberrancies a ...[more]

PMID: 31597639

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Project description:Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel. Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-β. A more detailed study of a second cohort with 18 potential autoantibody targets revealed marked heterogeneity in autoantibody responses against islet cell autoantigens including two polymorphic variants of ZnT8. A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). Although a few T1D subjects showed autoantibodies against a lung-associated protein KCNRG (6%) and S100-β (8%), no statistically significant autoantibodies were detected against several cytokines. Analysis of the overall autoantibody profiles using a heatmap revealed two major subgroups of approximately similar numbers, consisting of T1D subjects with and without organ-specific autoantibodies. Within the organ-specific subgroup, there was minimal overlap among anti-gastric ATPase, anti-thyroid peroxidase, and anti-transglutaminase seropositivity, and these autoantibodies did not correlate with islet cell autoantibodies. Examination of a third cohort, comprising prospectively collected longitudinal samples from high-risk individuals, revealed that anti-gastric ATPase autoantibodies were present in several individuals prior to detection of islet autoantibodies and before clinical onset of T1D. Taken together, these results suggest that autoantibody portraits derived from islet and organ-specific targets will likely be useful for enhancing the clinical management of T1D.

Project description:BackgroundIslet autoantibodies occur in type 2 diabetes. Our study aimed to investigate the prevalence of positive islet autoimmunity in community patients with type 2 diabetes.MethodsA total of 495 community patients with type 2 diabetes were recruited using the method of cluster sampling in this cross-sectional study. Three islet autoantibodies including glutamic acid decarboxylase antibody (GADA), insulin autoantibody (IAA) and islet cell antibody (ICA) were measured, and clinical characteristics involved in those individuals were evaluated.ResultsThe positive rate of islet autoantibodies was 28.5% in total, while combinations of different autoantibodies were rarely seen. Compared with GADA-negative group, positive counterparts significantly tended to have lower levels of body mass index (BMI), waist-hip ratio (WHR), and urinary microalbumin (mALB) (P < 0.05). Adjusted for confounding factors, WHR, triglycerides (TG), and mALB seemed to be negative independent predictors of GADA (OR < 1, P < 0.05). Patients with positive IAA tended to receive insulin treatment (P < 0.0001). Besides, fasting blood glucose (FBG), serum levels of high-density lipoprotein cholesterol (HDL-CH), aspartate transaminase (AST), and γ-glutamyltransferase (GGT) were more likely to be higher in IAA positive subgroup in comparison with the negative counterparts. While after AST was adjusted by unconditional logistic regression analysis, history of insulin treatment, FBG, HDL-CH, and GGT were confirmed as positive predictors of IAA. Furthermore, in patients who were IAA positive, those treated with exogenous insulin tended to have longer duration of diabetes than non-insulin treatment counterparts (P < 0.0001). With regard to ICA, however, there were no significant differences between the two subgroups, except that serum level of AST/ALT seemed to be slightly different (P = 0.064).ConclusionThese data suggested that type 2 diabetic community patients with positive GADA tended to be lean and were able to maintain normal lipid metabolism, while patients with positivity of IAA were frequently accompanied with insulin treatment and more closely associated with diabetic liver damage.

Dataset Information

Temporal Analysis of Amylase Expression in Control, Autoantibody-Positive, and Type 1 Diabetes Pancreatic Tissues.

Publications

Temporal Analysis of Amylase Expression in Control, Autoantibody-Positive, and Type 1 Diabetes Pancreatic Tissues.

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