The impact of substance P on the pathogenesis of insulin resistance leading to gestational diabetes.
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 &#946; (IKK &#946;), 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.
Jolanta
J
Patro-Malysza
Zaneta
Z
Kimber-Trojnar
Katarzyna
K
Skorzynska-Dziduszko
Beata
B
Marciniak
Dorota
D
Darmochwal-Kolarz
Jacek
J
Bartosiewicz
Bozena
B
Leszczynska-Gorzelak
Department of Obstetrics and Perinatology, Medical University of Lublin, ul. Jaczewskiego 8, 20-954 Lublin, Poland. jolapatro@wp.pl.
Jan
J
Oleszczuk
D000818:Animals; D016640:Diabetes, Gestational / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D011247:Pregnancy; D013373:Substance P / Q000378:metabolism*
D013373:Substance P