The neuropeptide substance P/neurokinin‐1 receptor system and diabetes: From mechanism to therapy

Abstract

Diabetes is a significant public health issue known as the world's fastestgrowing disease condition. It is characterized by persistent hyperglycemia and subsequent chronic complications leading to organ dysfunction and, ultimately, the failure of target organs. Substance P (SP) is an undecapeptide that belongs to the family of tachykinin (TK) peptides. The SP-mediated activation of the neurokinin 1 receptor (NK1R) regulates many pathophysiological processes in the body. There is also a relation between the SP/NK1R system and diabetic processes. Importantly, deregulated expression of SP has been reported in diabetes and diabetes-associated chronic complications. SP can induce both diabetogenic and antidiabetogenic effects and thus affect the pathology of diabetes destructively or protectively. Here, we review the current knowledge of the functional relevance of the SP/NK1R system in diabetes pathogenesis and its exploitation for diabetes therapy. A comprehensive understanding of the role of the SP/NK1R system in diabetes is expected to shed further light on developing new therapeutic possibilities for diabetes and its associated chronic conditions.

Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry

“…Impairment of adenosine kinase in GDM, the main regulator of adenosine levels, results in alterations in methylation-dependent gene expression regulation mechanisms that are essential for fetal programming [22]. Substance P (SP) is a member of the tachykinin (TK) peptides family and mediates activation of the neurokinin 1 receptor (NK1R), thus modifying multiple pathophysiologic processes in the organism [23]. SP is a neurotransmitter secreted by nerve endings, various non-neuronal cells, monocytes, and macrophages [24].…”

“…Fu et al investigated associations between SP, interleukin 6 (IL-6), and c-reactive protein (CRP) with T2DM and found higher SP, IL-6, and CRP concentrations, higher values of homeostatic model assessment-insulin resistance (HOMA-IR) in obese patients with T2DM and a positive correlation between body mass index (BMI), logHOMA-IR, and SP [27]. However, the overall effect of SP on diabetes may be ambivalent, with studies reporting both diabetogenic and anti-diabetogenic effects [23]. SP is considered to be a crucial neurotransmitter in the pancreas that additionally influences pancreatic secretion [23].…”

“…However, the overall effect of SP on diabetes may be ambivalent, with studies reporting both diabetogenic and anti-diabetogenic effects [23]. SP is considered to be a crucial neurotransmitter in the pancreas that additionally influences pancreatic secretion [23]. Murine models showed that individuals with NK1R deficiency when fed with a high-fat diet had lower weight gain and reduced levels of circulating leptin and insulin in their blood [28].…”