Beta-cell hypertrophy in fa/fa rats is associated with basal glucose hypersensitivity and reduced SNARE protein expression

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 5; pp. 997 - 1005
• Main Authors: CHAN, C. B, MACPHAIL, R. M, SHEU, L, WHEELER, M. B, GAISANO, H. Y
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.05.1999
• Subjects: Animals; Biological and medical sciences; Blood Glucose - metabolism; Exocytosis; Female; Glucose; Glucose - pharmacology; Hypertrophy; Insulin; Insulin - blood; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Medical sciences; Membrane Proteins - analysis; Metabolic diseases; Morphology; Nerve Tissue Proteins - analysis; Obesity; Obesity - pathology; Obesity - physiopathology; Proteins; Qa-SNARE Proteins; R-SNARE Proteins; Rats; Rats, Zucker; Signal transduction; SNARE Proteins; Synaptosomal-Associated Protein 25; Syntaxin 1; Vesicular Transport Proteins; Canada; Hyperinsulinemia; Animal model; Obesity; Pancreatic hormone; Pathophysiology; Rat; Langerhans islet; Rodentia; Insulin; Metabolic disorder; Vertebrata; Mammalia; B-Cell; Glycemia; Endocrine pancreas; Hypertrophy
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.5.997

Beta-cell hypertrophy in fa/fa rats is associated with basal glucose hypersensitivity and reduced SNARE protein expression. C B Chan , R M MacPhail , L Sheu , M B Wheeler and H Y Gaisano Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada. cchan@upei.ca Abstract In normal isolated beta-cells, the response to glucose is heterogeneous and characterized by an increasing number of secretory cells as glucose concentration rises (Pipeleers DG, Kiekens R, Ling Z, Wilikens A, Schuit F: Physiologic relevance of heterogeneity in the pancreatic beta-cell population. Diabetologia 37 (Suppl. 2):S57-S64, 1994). We hypothesized that fasting hyperinsulinemia in obesity might be explained by altered beta-cell heterogeneity of signal transduction mechanisms, possibly involving exocytotic proteins. Insulin secretion from individual beta-cells sorted according to the size of the islet donor (<125 microm, >250 microm, and intermediate diameter) was measured by reverse hemolytic plaque assay. Beta-cells from fa/fa rats were hypertrophied 25-40%, independent of donor islet size. This was accompanied by an increased proportion of secretory cells (recruitment) at 5.5-11.0 mmol/l glucose, increased secretion per cell at 2.8 mmol/l glucose, and decreased insulin content after acute glucose exposure without an increase in secretion per cell. Decreased expression of exocytotic (soluble N-ethylmaleimide-sensitive fusion protein receptor [SNARE]) proteins, vesicle-associated membrane protein isoform 2 (VAMP-2), synaptosomal protein of 25 kDa (SNAP-25), and syntaxin-1 and -2 in fa/fa beta-cells may contribute to the failure to sustain excessive plaque size at higher glucose concentrations. Fasting hyperinsulinemia may be maintained by increased recruitment and an exaggerated secretory response in all fa-derived islet populations. Glucose regulates beta-cell responsiveness in the short term, and these effects may involve altered expression of SNARE proteins.