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JTT‐608 restores impaired early insulin secretion in diabetic Goto‐Kakizaki rats
Author(s) -
Ohta Takeshi,
Furukawa Noboru,
Komuro Goro,
Yonemori Fumihiko,
Wakitani Korekiyo
Publication year - 1999
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702481
Subject(s) - tolbutamide , medicine , endocrinology , insulin , diabetes mellitus , postprandial , secretion , insulin oscillation , chemistry , insulin resistance
We investigated the pharmacological effects of a new antidiabetic agent, JTT‐608, in comparison with the sulphonylurea tolbutamide, in Goto‐Kakizaki (GK) rats, a genetic model of non‐obese insulin‐dependent diabetes mellitus (NIDDM). In isolated perfused pancreas from GK rats, JTT‐608 (200 μ M ) enhanced 11.1 m M glucose‐stimulated insulin secretion in the first and second phases, but had little effect on insulin secretion at 2.8 m M glucose. In contrast, tolbutamide (100 μ M ) markedly stimulated insulin secretion at 2.8 m M glucose and enhanced the second phase of insulin secretion but not the first phase at 11.1 m M glucose.In vivo JTT‐608 also enhanced early insulin secretion only with glucose‐loading. In contrast, tolbutamide enhanced insulin secretion both with and without glucose‐loading. JTT‐608 (10–100 mg kg −1 ) improved oral glucose tolerance with enhanced insulin secretion in a meal tolerance test (MTT). In comparison with tolbutamide, JTT‐608 improved glucose tolerance more efficiently in GK rats than in Wistar rats. We conclude that in diabetic GK rats JTT‐608 suppressed postprandial glucose excursions with enhanced glucose‐stimulated insulin secretion, especially the first phase of insulin secretion.British Journal of Pharmacology (1999) 126 , 1674–1680; doi: 10.1038/sj.bjp.0702481