We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Recovered Insulin Exocytosis by Long-Term Glinide Treatment in Diabetic GK Rats Analyzed by TIRF Microscopy.
- Authors
Kawai, Junko; Ohara-Imaizumi, Mica; Nakamichi, Yoko; Kikuta, Toshiki; Hatta, Maiko; Okamura, Tadashi; Watada, Hirotaka; Kawamori, Ryuzo; Nagamatsu, Shinya
- Abstract
It is unclear if long term-treatment of diabetic GK rat with nateglinide improves the insulin release. In the present study, we administrated nateglinide (Nate), glibenclamide (Gli), insulin (Ins), and vehicle (GKv) for 7 weeks to diabetic GK rats, and then examined the beta-cell functions using TIRF microscopy. Because the expression of exocytosis-related protein (SNAREs) is known to decrease in diabetes, we first examined the expression of syntaxin 1A and SNAP-25 proteins by immunohistochemistry and TIRF microscopy. The number of syntaxin I and SNAP-25 clusters in the plasma membrane analyzed by TIRF increased in Nate-, Ins- and Gli- treated GK beta-cells. In accordance with this increase, the number of insulin granules docked to the plasma membrane was markedly increased in Nate- and Ins-treated GK beta-cells (Cont, 310.2±16.3 : GKv, 96.7±5.6 : Nate, 249.4±11.0 : Ins, 210.1±9.7 per 200um²), but not in Gli-treated GK beta-cells (Gli, 148.5±15.1 per 200um²). We then examined the real-time motion of insulin granules using TIRFM analysis. Beta-cells were prepared from drug-treated GK rats, then infected with insulin-GFP adenovirus in order to label the insulin granules. We observed the fusion from previously docked granules stimulated by 16.7mM glucose in Nate- and Ins- treated GK beta-cells, in spite of little fusion observed in GKv and Gli-treated beta-cells. OGTT showed the improved glucose tolerance in Nate-, Gli-, and Ins-treated GK rats. Our data indicate that long-term Nate-treatment in GK rats improves the expression of SNAREs, docking status of insulin granules and fusion from them in diabetic beta-cells.
- Subjects
INSULIN; EXOCYTOSIS; HYPOGLYCEMIC agents; FLUORESCENCE microscopy; PANCREATIC beta cells; LABORATORY rats
- Publication
Diabetes, 2007, Vol 56, pA382
- ISSN
0012-1797
- Publication type
Article