Glucose-induced Translational Control of Proinsulin Biosynthesis Is Proportional to Preproinsulin mRNA Levels in Islet β-Cells but Not Regulated via a Positive Feedback of Secreted Insulin*

Proinsulin biosynthesis is regulated in response to nutrients, most notably glucose. In the short term (≤2h) this is due to increases in the translation of pre-existing mRNA. However, prolonging glucose stimulation (24 h) also increases preproinsulin mRNA levels. It has been proposed that secreted insulin from the pancreatic β-cell regulates its own synthesis through a positive autocrine feedback mechanism. Here the comparative contributions of translation and mRNA levels on the levels of proinsulin biosynthesis were examined in isolated pancreatic islets. Also, the autocrine role of insulin upon four β-cell functions (insulin secretion, proinsulin translation, preproinsulin mRNA levels, and total protein synthesis) was investigated in parallel. The results showed that proinsulin biosynthesis is regulated, in the short term (1 h), solely at the level of translation, through an ∼6-fold increase in response to glucose (2.8 mm versus 16.7 mm glucose). In the longer term, when preproinsulin mRNA levels have increased ∼2-fold, a corresponding increase was observed in the fold response of proinsulin translation to a stimulatory glucose concentration (≥10-fold). Importantly, neither exogenously added nor secreted insulin were found to play any role in regulating insulin secretion, proinsulin translation, preproinsulin mRNA levels, or total protein synthesis. The results presented here indicate that long term nutritional state sets the preproinsulin mRNA level in the β-cell at which translation control regulates short term changes in rates of proinsulin biosynthesis in response to glucose, but this is not mediated by any autocrine effect of insulin.

• Publication year

  2003

• Venue

  Journal of Biological Chemistry

• Publication date

  2003-10-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M303509200PMID 12928442
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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