Blockade of IRS1 in isolated rat pancreatic islets improves glucose-induced insulin secretion.
Several neural, hormonal and biochemical inputs actively participate in the balance of insulin secretion induced by blood glucose fluctuations. The exact role of insulin as an autocrine and paracrine participant in the control of its own secretion remains to be determined, mostly due to insufficient knowledge about the molecular phenomena that govern insulin signaling in pancreatic islets. In the present experiments we demonstrate that higher insulin receptor and insulin receptor substrates-1 and -2 (IRS1 and IRS2) concentrations are predominantly encountered in cells of the periphery of rat pancreatic islets, as compared to centrally located cells, and that partial blockade of IRS1 protein expression by antisense oligonucleotide treatment leads to improved insulin secretion induced by glucose overload, which is accompanied by lower steady-state glucagon secretion and blunted glucose-induced glucagon fall. These data reinforce the inhibitory role of insulin upon its own secretion in isolated, undisrupted pancreatic islets.
Araujo
Eliana P
EP
Department of Physiology and Biophysics, University of Campinas, Campinas, Brazil.
Amaral
Maria E C
ME
Souza
Cláudio T
CT
Bordin
Silvana
S
Ferreira
Fabiano
F
Saad
Mario J A
MJ
Boschero
Antonio C
AC
Magalhães
Everardo C
EC
Velloso
Lício A
LA
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005947:Glucose / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010750:Phosphoproteins / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D017931:DNA Primers; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D005947:Glucose