Antihyperglycemic effect of aporphines and their derivatives in normal and diabetic rats.
The antihyperglycemic actions of some aporphines and their derivatives in normal Wistar, streptozotocin (STZ)-induced diabetic (IDDM) and nicotinamide-STZ induced diabetic (NIDDM) rats were investigated in this study. These compounds included thaliporphine, glaucine, boldine, N-methyllaurotetanine, and predicentrine and the derivatives, N-[2-(2-methoxyphenoxy)ethyl]norglaucine and diacetyl- N-allylsecoboldine. Bolus intravenous injection of these compounds decreased the plasma glucose levels in a dose-dependent manner in both normal and diabetic rats. Among them, thaliporphine was found to have the most potent antihyperglycemic effect in both NIDDM and IDDM diabetic rats. It was found that thaliporphine could stimulate the release of insulin in both normal and diabetic rats, and a dose of 1 mg per kg thaliporphine could significantly attenuate the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. Similar treatment with thaliporphine significantly increased the skeletal muscle glycogen synthesis in both normal and diabetic rats. Hence, the hypoglycemic effect of thaliporphine in diabetic rats could be attributed to the stimulation of insulin release and the increase of glucose utilization.
Chi
Tzong-Cherng
TC
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lee
Shoei-Sheng
SS
Su
Ming-Jai
MJ
D000818:Animals; D001060:Aporphines / Q000737:chemistry / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000627:therapeutic use*; D007328:Insulin / Q000819:agonists; D008297:Male; D009536:Niacinamide; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D001060:Aporphines; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D009536:Niacinamide; C080702:thaliporphine