Relation of insulin deficiency to impaired insulin action in NIDDM adult rats given streptozocin as neonates.
We assessed the impact of chronic insulin deficiency on basal and insulin-stimulated glucose utilization by the whole-body mass in vivo in female albino Wistar rats. This assessment was based on a comparison of results in rats given streptozocin (STZ) on day of birth (n0-STZ), when 2 days old (n2-STZ), or when 5 days old (n5-STZ). At 10 wk of age, the n2-STZ rats exhibited characteristics similar to those obtained in the n0-STZ rats: normal growth, modest elevation of basal plasma glucose (8.23 +/- 0.24 mM), glucose intolerance, depleted pancreatic insulin stores (approximately 50% of normal value), and lack of insulin release in response to glucose in vivo. In contrast, the n5-STZ rats exhibited frank basal hyperglycemia (glucose 11.9 +/- 1.1 mM) and glucose intolerance, increased glycosylated hemoglobins, strong reduction of the pancreatic insulin stores (10% of normal value), decreased basal plasma insulin levels (50% of normal value), and lack of insulin release in response to glucose in vivo. Changes in the sensitivity of the neonatal beta-cell to STZ and the regeneration capacity of the beta-cells during the 1st postnatal wk were liable factors for the contrast. In vivo insulin action was assessed with the euglycemic-hyperinsulinemic clamp technique in 10-wk-old anesthetized animals. In the n2-STZ rats compared with controls 1) endogenous glucose production was significantly higher despite a normal plasma insulin level in the basal state, 2) endogenous glucose production rate was similarly suppressed by hyperinsulinemia, and 3) glucose utilization by the whole-body mass was similarly increased by hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Blondel
O
O
Laboratory of Developmental Physiology, University of Paris, France.
Bailbé
D
D
Portha
B
B
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D005947:Glucose