Decreased islet sensitivity to insulin in hamsters with dietary-induced insulin resistance.
In the present study, we evaluated the autocrine modulatory effect of insulin on glucose metabolism and glucose-induced insulin secretion in islets isolated from hamsters with insulin resistance (IR) induced by administration of a sucrose-rich diet (SRD) during 5 weeks. We used an approach of two metabolic pathways (glucose oxidation and utilization) based on the measurement of 14CO2 and 3H2O production from D-[U-14C]-glucose and D-[5-(3)H]-glucose, respectively, in isolated islets incubated with 3.3 and 16.7 mM glucose alone, or with 5 or 15 mU/ml insulin, anti-insulin guinea-pig serum (1:500), 25 microM nifedipine, or 150 nM wortmannin. Insulin release was measured by radioimmunoassay in islets incubated with 3.3 or 16.7 mM glucose, with or without 75, 150, and 300 nM wortmannin. Results showed that the stimulatory effect of insulin upon 14CO2 and 3H2O production in control islets was not observed in SRD islets. Addition of anti-insulin serum, nifedipine or wortmannin to the medium with 16.7 mM glucose decreased 14CO2 and 3H2O production in control but not in SRD islets. Whereas wortmannin did not decrease insulin release induced by 16.7 mM glucose in SRD hamsters, it did in controls. We can conclude that the autocrine stimulatory effect of insulin upon glucose metabolism observed in normal islets is attenuated or even absent in islets from IR animals. Such decreased islet sensitivity to insulin did not prevent the compensatory secretion of insulin from maintaining glucose homeostasis, suggesting that, at least in this model, the islets can put forward alternative mechanisms to overcome such defect.
Francini
Flavio
F
CENEXA-Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET, PAHO/WHO Collaborating Center), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 1900 La Plata, Argentina.
Gagliardino
Juan J
JJ
Borelli
María I
MI
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001834:Body Water / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002245:Carbon Dioxide / Q000378:metabolism; D006224:Cricetinae; D004032:Diet; D004326:Drinking / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008647:Mesocricetus; D009543:Nifedipine / Q000494:pharmacology; D010084:Oxidation-Reduction; D014867:Water / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D002121:Calcium Channel Blockers; D007004:Hypoglycemic Agents; D007328:Insulin; D007329:Insulin Antagonists; D014867:Water; D002245:Carbon Dioxide; D009543:Nifedipine; D005947:Glucose; D000077191:Wortmannin