Role of POMC and AgRP neuronal activities on glycaemia in mice

Autor: Paula G.F. Quaresma, Young-Bum Kim, Michelle Chung, Aykut Göktürk Üner, Onur Keçik, Wenjing Li, Thiago M. de Araújo, Christian Bjørbæk, Hyon Lee, Hyun Jeong Kim
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
Scientific Reports
ISSN: 2045-2322
Popis: 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.
Databáze: OpenAIRE
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