Compound M & B 39890A [N-(3-imidazol-1-ylpropyl)- 2-(3-trifluoromethylbenezensulphonamido)-benzamide hydrochloride], a glucagon and insulin secretion inhibitor, improves insulin sensitivity in viable yellow obese-diabetic mice.

Compound M & B 39890A [N-(3-imidazol-1-ylpropyl)-2- (3-trifluoromethylbenzenesulphonamido)benzamide hydrochloride] had no effect on cellular cAMP and cGMP levels but significantly inhibited insulin and glucagon secretion from freshly isolated normal rat islets stimulated with 10 mM glucose and 20 mM arginine. Daily gavage of the compound for three days lowered the elevated blood glucose and plasma insulin levels in fed, male viable yellow obese-diabetic mice; the minimum effective dose was 25 mg/kg. However, M & B 39890A did not affect the blood glucose level of fasted diabetic mice.

Antidiabetic activity of MTP-3115 in normal and diabetic mice.

MTP-3115 is a newly-synthesized thiopyranopyrimidine compound with a structure similar to that of MTP-1403 and MTP-1307. However, the biological profile of MTP-3115 is different from that of MTP-1403 and MTP-1307 (previously reported). Similar to MTP-1403 and MTP-1307, MTP-3115 improves glucose tolerance in both normal and obese-diabetic viable yellow mice with equal potency.

Effects of LY104119, a thermogenic weight-reducing compound, on norepinephrine concentrations and turnover in obese and lean mice.

Dopamine (DA) accumulation in interscapular brown adipose tissue (IBAT), heart, and liver was linear for more than 60 min after injection of 1-cyclohexyl-2-mercapto-imidazole (CHMI), a DA beta-hydroxylase inhibitor, into mice and served as an index of the rate of synthesis of norepinephrine (NE) in these tissues. There was a marked diurnal rhythm of DA accumulation in all three tissues of mice fed ad libitum, the rhythm being dampened in obese mice in IBAT and liver but not in heart. LY104119 acutely decreased NE concentration in IBAT, heart and liver, but not in brain, and it also decreased DA accumulation after CHMI in IBAT, heart and liver.