Dataset Information

Small human islets comprised of more ?-cells with higher insulin content than large islets.

ABSTRACT: For the past 30 years, data have suggested that unique islet populations exist, based on morphology and glucose sensitivity. Yet little has been done to determine the mechanism of these functional differences. The purpose of this study was to determine whether human islets were comprised functionally unique populations, and to elucidate a possible mechanism. Islets or pancreatic sections from 29 human donors were analyzed. Islets were isolated and measured for insulin secretion, cell composition and organization, insulin and glucagon granule density and insulin content. Insulin secretion was significantly greater in small compared with large islets. In sectioned human pancreata, ?-cells comprised a higher proportion of the total endocrine cells in small islets (63%) than large islets (39%). A higher percentage of ?-cells in small islets contacted blood vessels (44%) compared with large islets (31%). Total insulin content of isolated human islets was significantly greater in the small (1323 ± 512 ?IU/IE) compared with large islets (126 ± 48 ?IU/IE). There was less immunostaining for insulin in the large islets from human pancreatic sections, especially in the core of the islet, compared with small islets. The results suggest that differences in insulin secretion between large and small islets may be due to a higher percentage of ?-cells in small islets with more ?-cells in contact with blood vessels and a higher concentration of insulin/?-cell in small islets.

SUBMITTER: Farhat B

PROVIDER: S-EPMC4204020 | biostudies-literature | 2013 Mar-Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Small human islets comprised of more β-cells with higher insulin content than large islets.

Farhat Bilal B Almelkar Akshay A Ramachandran Karthik K Williams S Janette SJ Huang Han-Hung HH Zamierowksi David D Novikova Lesya L Stehno-Bittel Lisa L

Islets 20130301 2

For the past 30 years, data have suggested that unique islet populations exist, based on morphology and glucose sensitivity. Yet little has been done to determine the mechanism of these functional differences. The purpose of this study was to determine whether human islets were comprised functionally unique populations, and to elucidate a possible mechanism. Islets or pancreatic sections from 29 human donors were analyzed. Islets were isolated and measured for insulin secretion, cell composition ...[more]

PMID: 23648896

Similar Datasets

Project description:PurposeType 1 diabetes (T1D) accounts for an estimated 5% of all diabetes in the United States, afflicting over 1.25 million individuals. Maintaining long-term blood glucose control is the major goal for individuals with T1D. In T1D, insulin-secreting pancreatic islet β-cells are destroyed by the immune system, but glucagon-secreting islet α-cells survive. These remaining α-cells no longer respond properly to fluctuating blood glucose concentrations. Dysregulated α-cell function contributes to hyper- and hypoglycemia which can lead to macrovascular and microvascular complications. To this end, we sought to discover small molecules that suppress α-cell function for their potential as preclinical candidate compounds. Prior high-throughput screening identified a set of glucagon-suppressing compounds using a rodent α-cell line model, but these compounds were not validated in human systems.ResultsHere, we dissociated and replated primary human islet cells and exposed them to 24 h treatment with this set of candidate glucagon-suppressing compounds. Glucagon accumulation in the medium was measured and we determined that compounds SW049164 and SW088799 exhibited significant activity. Candidate compounds were also counter-screened in our InsGLuc-MIN6 β-cell insulin secretion reporter assay. SW049164 and SW088799 had minimal impact on insulin release after a 24 h exposure. To further validate these hits, we treated intact human islets with a selection of the top candidates for 24 h. SW049164 and SW088799 significantly inhibited glucagon release into the medium without significantly altering whole islet glucagon or insulin content. In concentration-response curves SW088799 exhibited significant inhibition of glucagon release with an IC50 of 1.26 µM.ConclusionGiven the set of tested candidates were all top hits from the primary screen in rodent α-cells, this suggests some conservation of mechanism of action between human and rodents, at least for SW088799. Future structure-activity relationship studies of SW088799 may aid in elucidating its protein target(s) or enable its use as a tool compound to suppress α-cell activity in vitro.

Dataset Information

Small human islets comprised of more ?-cells with higher insulin content than large islets.

Publications

Small human islets comprised of more β-cells with higher insulin content than large islets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets