Role of substance P in the regulation of glucose metabolism via insulin signaling-associated pathways

Iordanes Karagiannides, Kyriaki Bakirtzi, Efi Kokkotou, Dimitris Stavrakis, Kara Gross Margolis, Thomas Thomou, Nino Giorgadze, James L Kirkland, Charalabos Pothoulakis

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Substance P (SP), encoded by the tachykinin 1 (Tac1) gene, is the most potent tachykinin ligand for the high-affinity neurokinin-1 receptor (NK-1R).Wepreviously reported that NK-1R-deficient mice show less weight gain and reduced circulating levels of leptin and insulin in response to a high-fat diet (HFD) and demonstrated the presence of functional NK-1R in isolated human preadipocytes. Here we assessed the effects of SP on weight gain in response to HFD and determined glucose metabolism in Tac1-deficient (Tac1-/-) mice. The effect of SP on the expression of molecules that may predispose to reduced glucose uptake was also determined in isolated human mesenteric, omental, and sc preadipocytes. We show that although weight accumulation in response to HFD was similar between Tac1-/- mice and wild-type littermates, Tac1-/- mice demonstrated lower glucose and leptin and increased adiponectin blood levels and showed improved responses to insulin challenge after HFD. SP stimulated phosphorylation of c-Jun N-terminal kinase, protein kinase Cθ, mammalian target of rapamycin, and inhibitory serine insulin receptor substrate-1 phosphorylation in human preadipocytes in vitro. Preincubation of human mesenteric preadipocytes with the protein kinase Cθ pseudosubstrate inhibitor reduced insulin receptor substrate 1 phosphorylation in response to SP. Lastly, SP also induced insulin receptor substrate-1 phosphorylation in maturehumansc adipocytes. Our results demonstrate an important role for SP in adipose tissue responses and obesity-associated pathologies. These novel SP effects on molecules that enhance insulin resistance at the adipocyte level may reflect an important role for this peptide in the pathophysiology of type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)4571-4580
Number of pages10
JournalEndocrinology
Volume152
Issue number12
DOIs
StatePublished - Dec 2011

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Substance P
Tachykinins
Insulin
Glucose
High Fat Diet
Neurokinin-1 Receptors
Insulin Receptor Substrate Proteins
Phosphorylation
Leptin
Adipocytes
Protein Kinase C
Weight Gain
JNK Mitogen-Activated Protein Kinases
Adiponectin
Sirolimus
Type 2 Diabetes Mellitus
Insulin Resistance
Adipose Tissue
Obesity
Pathology

ASJC Scopus subject areas

  • Endocrinology

Cite this

Karagiannides, I., Bakirtzi, K., Kokkotou, E., Stavrakis, D., Margolis, K. G., Thomou, T., ... Pothoulakis, C. (2011). Role of substance P in the regulation of glucose metabolism via insulin signaling-associated pathways. Endocrinology, 152(12), 4571-4580. https://doi.org/10.1210/en.2011-1170

Role of substance P in the regulation of glucose metabolism via insulin signaling-associated pathways. / Karagiannides, Iordanes; Bakirtzi, Kyriaki; Kokkotou, Efi; Stavrakis, Dimitris; Margolis, Kara Gross; Thomou, Thomas; Giorgadze, Nino; Kirkland, James L; Pothoulakis, Charalabos.

In: Endocrinology, Vol. 152, No. 12, 12.2011, p. 4571-4580.

Research output: Contribution to journalArticle

Karagiannides, I, Bakirtzi, K, Kokkotou, E, Stavrakis, D, Margolis, KG, Thomou, T, Giorgadze, N, Kirkland, JL & Pothoulakis, C 2011, 'Role of substance P in the regulation of glucose metabolism via insulin signaling-associated pathways', Endocrinology, vol. 152, no. 12, pp. 4571-4580. https://doi.org/10.1210/en.2011-1170
Karagiannides I, Bakirtzi K, Kokkotou E, Stavrakis D, Margolis KG, Thomou T et al. Role of substance P in the regulation of glucose metabolism via insulin signaling-associated pathways. Endocrinology. 2011 Dec;152(12):4571-4580. https://doi.org/10.1210/en.2011-1170
Karagiannides, Iordanes ; Bakirtzi, Kyriaki ; Kokkotou, Efi ; Stavrakis, Dimitris ; Margolis, Kara Gross ; Thomou, Thomas ; Giorgadze, Nino ; Kirkland, James L ; Pothoulakis, Charalabos. / Role of substance P in the regulation of glucose metabolism via insulin signaling-associated pathways. In: Endocrinology. 2011 ; Vol. 152, No. 12. pp. 4571-4580.
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