Background: Islet cell transplantation is a novel therapeutic modality for the cure of diabetes. Pig islet cells are an attractive substitute for human islet cells; however, they are known to be particularly difficult to isolate because of a weak islet capsule and a tendency to be fragmented during enzymatic digestion. Therefore, parameters favoring successful pig islet isolation were investigated using specific-pathogen-free (SPF) miniature pigs.
Methods: Sixty-eight SPF miniature pigs were used for islet isolation. Birth weight, body weight, age, sex, pregnancy history, and the fasting blood glucose levels of each pig were determined. Each pig's general condition was assessed with regard to feeding status and physical activity. Pancreas procurement was performed by one surgical team. Anesthesia duration, operation duration, procedure quality, and perfusate type were recorded. After pancreatectomy, a biopsy was performed for islet density analysis. Decapsulation, cannulation duration, degree of distension, and cold ischemic time were assessed. During islet isolation, pancreas weight, digestion time, and digested tissue proportion were recorded. Isolation results were evaluated by total islet equivalents (IEQ), islet equivalents per gram of pancreas (IEQ/g), isolation index, islet recovery rate, purity, and visual grade. To identify the predictors of higher islet isolation yield, we performed binary logistic regression analysis with significant (P < 0.05) variables from the univariate analysis.
Results: The pigs were categorized into high (n = 34) and low yield (n = 34) groups according to the median IEQ/g or total IEQ values. Body weight and age were significantly different between the two groups. Being male or a positive history of pregnancy in females was factors favoring successful islet isolation. General condition assessments failed to estimate islet isolation results. Long anesthesia duration, which might have caused ischemic injury to the pancreas, negatively affected islet isolation results. Decapsulation, cannulation duration, and subsequent pancreas distension were significantly important in successful islet isolation. Inter-lot variability of Liberase was not observed because of screening processes performed before purchase. Isolation index and islet recovery rate correlated well with islet yields.
Conclusions: Multivariate analysis using total IEQ and IEQ/g as outcome variables indicated that age older than 2, being male and moderate distension by Liberase injection are major determinants influencing successful islet isolation.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/j.1399-3089.2008.00504.x | DOI Listing |
Biomolecules
November 2024
Centre for Diabetes, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK.
Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are related intestinal L-cell derived secretory products. GLP-1 has been extensively studied in terms of its influence on metabolism, but less attention has been devoted to GLP-2 in this regard. The current study compares the effects of these proglucagon-derived peptides on pancreatic beta-cell function, as well as on glucose tolerance and appetite.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Department of Psychology, University of Miami, Coral Gables, FL, United States.
The neuropeptide oxytocin (OXT) and its receptor (OXTR) have been shown to play an important role in glucose metabolism, and pancreatic islets express this ligand and receptor. In the current study, OXTR expression was identified in α-, β-, and δ-cells of the pancreatic islet by RNA hybridization, and OXT protein expression was observed only in β-cells. In order to examine the contribution of islet OXT/OXTR in glycemic control and islet β-cell heath, we developed a β-cell specific OXTR knock-out (β-KO) mouse.
View Article and Find Full Text PDFβ-cell dysfunction in pancreatic islets, characterized as either the loss of β-cell mass or the resistance of β-cell to glucose, is the leading cause of progression to diabetes. Islet transplantation became a promising approach to replenish functional β-cell mass. However, not much known about changes in islets used for transplantation after isolation.
View Article and Find Full Text PDFHuman endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 115 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation.
View Article and Find Full Text PDFLife Sci
January 2025
Immuno-Endocrinology, Diabetes & Metabolism Laboratory, Instituto de Investigaciones en Medicina Traslacional (IIMT), CONICET - Universidad Austral, Pilar, Argentina; Facultad de Ciencias Biomédicas, , Universidad Austral, Pilar, Argentina. Electronic address:
Aims: Type 2 diabetes (T2D) is a prevalent metabolic disease linked to obesity and metabolic syndrome (MS). The glucolipotoxic environment (GLT) impacts tissues causing low-grade inflammation, insulin resistance and the gradual loss of pancreatic β-cell function, leading to hyperglycemia. We have previously shown that Compound A (CpdA), a plant-derived dissociative glucocorticoid receptor-modulator with inflammation-suppressive activity, displays protective effects on β-cells in type 1 diabetes murine models.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!