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. In addition, it had no effect on blood glucose levels of normal mice and streptozotocin-diabetic rats. M & B 39890A, fed in the diet at the concentration of 1 mg/g for 42 days, reversed the hyperglycemia of the fed diabetic mice without causing tachyphylaxis and improved the sensitivity to exogenous insulin as demonstrated by the lowering of blood glucose. When M & B 39890A was fed to young male mice destined to become diabetic, the development of hyperglycemia was prevented. Thus, M & B 39890A represents a new class of pharmacological agents that may prove to be effective for the chronic treatment of type II diabetics without the risk of hypoglycemia.
Yen
T T
TT
Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285.
Schmiegel
K K
KK
Gold
G
G
Williams
G D
GD
Dininger
N B
NB
Broderick
C L
CL
Gill
A M
AM
D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors*; D001786:Blood Glucose / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D004435:Eating / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D051381:Rats; D011919:Rats, Inbred Strains; D000096926:Benzenesulfonamides
D001120:Arginine; D001786:Blood Glucose; D005576:Colforsin; D005934:Glucagon; D007004:Hypoglycemic Agents; D007093:Imidazoles; D007328:Insulin; C052032:M&B 39890A; D000096926:Benzenesulfonamides