Development of hyperglycaemia and insulin resistance in conscious genetically diabetic (C57BL/KsJ-db/db) mice.
A bolus injection of insulin dose-dependently reduced plasma glucose levels in genetically diabetic (db/db) mice and their normoglycaemic litter-mates (+/+ mice) aged 5, 8 and 12 weeks. Compared between the groups, the dose-response curves showed that insulin resistance was already present in the 5-week-old db/db mice when they were still normoglycaemic. The minimum effective dose of insulin was lower in the +/+ (32 micrograms/kg) than in the db/db (100 micrograms/kg) mice and the maximum response which was obtained at 320-1000 micrograms/kg of the hormone was higher in the former (about 80%) than in the latter (about 55%). Although the basal plasma glucose levels in the db/db mice were significantly increased with age as compared with those in the +/+ mice, the insulin response curves were identical in the db/db mice from 5 to 12 weeks of age. The number of insulin binding sites were significantly decreased by 22-50% (5-12-week-old) in the liver plasma membrane from the db/db mice compared with that from the +/+ mice, while its affinity was not significantly changed between the groups. Streptozotocin (100 mg/kg, i.p.) treatment increased the number of insulin receptors in the db/db mice to a number comparable with those in the +/+ mice. Coinciding with the change, the hypoglycaemic action of insulin was slightly enhanced in the streptozotocin-treated db/db mice compared with that in non-treated db/db mice, but was still considerably depressed when compared with that in +/+ mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Kodama
H
H
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Ibaraki, Japan.
Fujita
M
M
Yamaguchi
I
I
D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D006943:Hyperglycemia / Q000235:genetics / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D013045:Species Specificity
D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin