Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion

Mayowa A. Osundiji, Daniel D. Lam, Jill Shaw, Chen-Yu Yueh, S. Pauliina Markkula, Paul Hurst, Carolina Colliva, Aldo Roda, Lora K. Heisler, Mark L. Evans*

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

As patients decline from health to type 2 diabetes, glucose-stimulated insulin secretion (GSIS) typically becomes impaired. Although GSIS is driven predominantly by direct sensing of a rise in blood glucose by pancreatic beta-cells, there is growing evidence that hypothalamic neurons control other aspects of peripheral glucose metabolism. Here we investigated the role of the brain in the modulation of GSIS. To examine the effects of increasing or decreasing hypothalamic glucose sensing on glucose tolerance and insulin secretion, glucose or inhibitors of glucolcinase, respectively, were infused into the third ventricle during intravenous glucose tolerance tests (IVGTTs). Glucose-infused rats displayed improved glucose handling, particularly within the first few minutes of the IVGTT, with a significantly lower area under the excursion curve within the first 10 min (AUC(0-10))). This was explained by increased insulin secretion. In contrast, infusion of the glucokinase inhibitors glucosarnine or mannoheptulose worsened glucose tolerance and decreased GSIS in the first few minutes of IVGTT. Our data suggest a role for brain glucose sensors in the regulation of GSIS, particularly during the early phase. We propose that pharmacological agents targeting hypothalamic glucose-sensing pathways may represent novel therapeutic strategies for enhancing early phase insulin secretion in type 2 diabetes. Diabetes 61:321-328, 2012

Original languageEnglish
Pages (from-to)321-328
Number of pages8
JournalDiabetes
Volume61
Issue number2
Early online date30 Dec 2011
DOIs
Publication statusPublished - Feb 2012

Keywords

  • in-vivo
  • beta-cells
  • rat-brain
  • glucokinase
  • hypoglycemia
  • plasma
  • homeostasis
  • impairment
  • expression
  • responses

Cite this

Osundiji, M. A., Lam, D. D., Shaw, J., Yueh, C-Y., Markkula, S. P., Hurst, P., Colliva, C., Roda, A., Heisler, L. K., & Evans, M. L. (2012). Brain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion. Diabetes, 61(2), 321-328. https://doi.org/10.2337/db11-1050