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PMID:12435589

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Citation

Araujo, EP, Amaral, ME, Souza, CT, Bordin, S, Ferreira, F, Saad, MJ, Boschero, AC, Magalhães, EC and Velloso, LA (2002) Blockade of IRS1 in isolated rat pancreatic islets improves glucose-induced insulin secretion. FEBS Lett. 531:437-42

Abstract

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.

Links

PubMed

Keywords

Animals; Base Sequence; DNA Primers; Glucose/pharmacology; Immunohistochemistry; Insulin/secretion; Insulin Receptor Substrate Proteins; Islets of Langerhans/drug effects; Islets of Langerhans/metabolism; Islets of Langerhans/secretion; Male; Phosphoproteins/antagonists & inhibitors; Rats; Rats, Wistar

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:INSR

involved_in

GO:0042327: positive regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:INSR

involved_in

GO:0032868: response to insulin

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:INSR

involved_in

GO:0009749: response to glucose

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:IRS1

involved_in

GO:0070094: positive regulation of glucagon secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:IRS1

involved_in

GO:0090275: negative regulation of somatostatin secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:IRS1

involved_in

GO:0046676: negative regulation of insulin secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:IRS1

involved_in

GO:0042327: positive regulation of phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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