The Impact of Substance P on the Pathogenesis of Insulin Resistance Leading to Gestational Diabetes
Jolanta Patro-Malysza, Zaneta Kimber-Trojnar, Katarzyna Skorzynska-Dziduszko, Beata Marciniak, Dorota Darmochwal-Kolarz, Jacek Bartosiewicz, Bozena Leszczynska-Gorzelak and Jan Oleszczuk
Affiliation: Department of Obstetrics and Perinatology, Medical University of Lublin, ul. Jaczewskiego 8, 20-954 Lublin, Poland.
Keywords: Gestational diabetes, insulin receptor substrate, insulin resistance, metabolism, pregnancy, substance P.
Gestational diabetes mellitus is one of the most often medical conditions during pregnancy affecting 5-6% of
all pregnancies. The etiology of gestational diabetes is not clearly understood. In obesity and diabetes mellitus type 2, abnormal
insulin signaling is an important agent mediating the increase of insulin resistance. Insulin receptor substrate serine
phosphorylation is a time-controlled physiological reaction in insulin signaling that has been disrupted by metabolic
and inflammatory stresses to support insulin resistance. Several kinases, including inhibitor of nuclear factor ĸB kinase
β (IKK β), c-Jun N-terminal kinase (JNK), mammalian target of rapamycin (mTOR), protein kinase C (PKC) and ribosomal
S6 protein kinase (S6K), are activated by these stimulators of insulin resistance and phosphorylate insulin receptor
substrate proteins on several serine residues in an uncontrollable method. There are an increasing number of data indicating
that substance P, being one of the crucial activators of these kinases, is a potent cytokine that impairs insulin signaling.
Here we discuss recent studies that expand our understanding of how substance P may contribute to the development of
insulin resistance. In our opinion, there are many interesting data suggesting that substance P may be a new player in the
pathogenesis of this unfavorable condition, leading not only to the development of diabetes mellitus type 2, but also gestational
diabetes. Since the etiology of gestational diabetes remains unclear, there is a strong need to explore new directions,
including those not directly associated with the canonical knowledge regarding this pathology.
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