Role of POMC and AgRP neuronal activities on glycaemia in mice

Research output: Contribution to journalArticle

Authors

  • Aykut Göktürk Üner
  • Onur Keçik
  • Paula G.F. Quaresma
  • Thiago M. De Araujo
  • Hyon Lee
  • Wenjing Li
  • Hyun Jeong Kim
  • Michelle Chung
  • Christian Bjørbæk
  • Young Bum Kim

External Institution(s)

  • Harvard University
  • Adnan Menderes University

Details

Original languageEnglish (US)
Article number13068
JournalScientific reports
Volume9
Issue number1
StatusPublished - Dec 1 2019
Peer-reviewedYes

Abstract

Leptin regulates both feeding and glycaemia primarily through its receptors expressed on agouti-related peptide (AgRP) and pro-opiomelanocortin-expressing (POMC) neurons; however, it is unknown whether activity of these neuronal populations mediates the regulation of these processes. To determine this, we injected Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) viruses into the hypothalamus of normoglycaemic and diabetic AgRP-ires-cre and POMC-cre mice to chemogenetically activate or inhibit these neuronal populations. Despite robust changes in food intake, activation or inhibition of AgRP neurons did not affect glycaemia, while activation caused significant (P = 0.014) impairment in insulin sensitivity. Stimulation of AgRP neurons in diabetic mice reversed leptin’s ability to inhibit feeding but did not counter leptin’s ability to lower blood glucose levels. Notably, the inhibition of POMC neurons stimulated feeding while decreasing glucose levels in normoglycaemic mice. The findings suggest that leptin’s effects on feeding by AgRP neurons are mediated by changes in neuronal firing, while the control of glucose balance by these cells is independent of chemogenetic activation or inhibition. The firing-dependent glucose lowering mechanism within POMC neurons is a potential target for the development of novel anti-diabetic medicines.

Citation formats

APA

Üner, A. G., Keçik, O., Quaresma, P. G. F., De Araujo, T. M., Lee, H., Li, W., ... Kim, Y. B. (2019). Role of POMC and AgRP neuronal activities on glycaemia in mice. Scientific reports, 9(1), [13068]. https://doi.org/10.1038/s41598-019-49295-7

Harvard

Üner, AG, Keçik, O, Quaresma, PGF, De Araujo, TM, Lee, H, Li, W, Kim, HJ, Chung, M, Bjørbæk, C & Kim, YB 2019, 'Role of POMC and AgRP neuronal activities on glycaemia in mice', Scientific reports, vol. 9, no. 1, 13068. https://doi.org/10.1038/s41598-019-49295-7