Ultrastructural and secretory heterogeneity of fa/fa (Zucker) rat islets

Molecular and Cellular Endocrinology
C B ChanK W Sulston

Abstract

Many previous studies of obese rodents documented biochemical changes in pancreatic islets that contribute to hyperinsulinemia in vivo. Those studies used heterogeneous populations of islets, although the size of islets from obese rats ranges from < 100 to > 500 microm. Here, functional and morphological changes in size-sorted (< 125 and > 250 microm diameter) islets from obese Zucker (fa/fa) rats were correlated. Ultrastructural examination revealed that > 250 microm cultured islets had an increased number of immature secretory granules in the beta cells. The number of degranulated beta cells in > 250 and < 125 microm cultured islets from fa/fa rats was higher than in lean rat islets (33 vs 25%). The glucose EC50 values for cultured islets were 4.64 +/- 0.43, 7.9 +/- 0.70 and 7.29 +/- 1.64 mmol.l(-1) for > 250 microm, < 125 microm, and lean groups, respectively. Inhibition of insulin secretion by 10 mmol.l(-1) mannoheptulose was reduced by 50% in > 250 microm islets compared with small islets. Studies of individual beta cells by reverse hemolytic plaque assay revealed 3-fold more cells from > 250 microm islets were stimulated by 1.4 mmol.l(-1) glucose than cells from < 125 microm islets. We conclude that functional defects in ...Continue Reading

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Citations

Jul 26, 2008·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Morten Gram PedersenClaudio Cobelli
Feb 15, 2008·Diabetes/metabolism Research and Reviews·Monique C SalehCatherine B Chan
Dec 18, 2003·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·L G SøndergaardJ Rungby
May 10, 2008·Toxicologic Pathology·David A NugentHuw B Jones
Dec 22, 1999·Canadian Journal of Physiology and Pharmacology·C B Chan, J J Surette
Jan 27, 2004·The Journal of Pharmacology and Experimental Therapeutics·Shuhei TomimotoAkemichi Baba

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