Impaired in vivo insulin secretion in response to non-glucidic secretagogues in adult rats after neonatal streptozotocin.
In the perfused pancreas of adult rats that were injected with streptozotocin (STZ) during the neonatal period, the release of insulin caused by glucose is more severely affected than that evoked by other secretagogues. We have now examined whether a comparable situation prevails in vivo. In anesthetised rats, the 0-10 min plasma insulin incremental area recorded after intravenous glucose administration (2.8 mumol/g body wt) was severely decreased in STZ rats, with a K value for glucose utilization of 1.9 +/- 0.2 x 10(-2)/min, as compared with control rats, with a K value of 4.4 +/- 0.4 x 10(-2)/min. At the 2nd min of the test, the plasma insulin increment was about 5 times lower in STZ than control rats. After glibenclamide administration (0.1 nmol/g body wt), the insulin incremental area was 3 times lower in STZ than control rats. Relative to the post-prandial readings, the plasma glucose concentration was decreased to the same extent, however, in control and STZ rats injected with glibenclamide. The secretory response to succinic acid methyl ester (SAM; 1.0 mumol/g body wt) was virtually abolished in the STZ rats. In the latter animals, SAM also failed to enhance the hypoglycemic action of glibenclamide in contrast to the situation found in control rats. Iterative intraperitoneal administration of SAM (1.0 mumol/g body wt) thrice daily for 7-10 days failed to improve significantly the insulin secretory response to glucose or glibenclamide, whether in control or STZ rats. These findings indicate that the altered metabolism of glucose in the B cell of STZ rats coincides with an impaired secretory response to glibenclamide and SAM, as possibly attributable, in part at least, to a loss of the modulating action of glucose upon the secretory response to the hypoglycemic sulfonylurea and succinate ester.
Vicent
D
D
Fundacion Jimenez Diaz, Madrid, Spain.
Villanueva-Peñacarrillo
M L
ML
Valverde
I
I
Malaisse
W J
WJ
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013311:Streptozocin / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D013386:Succinates; D013311:Streptozocin; D005947:Glucose; D005905:Glyburide; C041105:monomethyl succinate