Neuropeptide�B stimulates insulin secretion and expression but not proliferation in rat insulin‑producing INS‑1E cells

Abstract

neuropeptide B (nPB) regulates food intake, body weight and energy homeostasis by interacting with nPBW1/nPBW2 in humans and nPBW1 in rodents. nPB and nPBW1 are widely expressed in the central nervous system and peripheral tissues including pancreatic islets. although previous studies have demonstrated a prominent role for nPB and nPBW1 in controlling glucose and energy homeostasis, it remains unknown as to whether nPB modulates pancreatic β-cell functions. Therefore, the aim of the present study was to investigate the effects of nPB on insulin expression and secretion in vitro. Furthermore, the role of nPB in the modulation of inS-1e cell growth, viability and death was examined. Gene expression was assessed by reverse transcription-quantitative Pcr. cell proliferation and viability were determined by Brdu or MTT tests, respectively. apoptotic cell death was evaluated by relative quantification histone-complexed DNA fragments (mono-and oligonucleosomes). insulin secretion was studied using an eliSa test. Protein phosphorylation was assessed by western blot analysis. nPB and nPBW1 mrna was expressed in inS-1e cells and rat pancreatic islets. in inS-1e cells, nPB enhanced insulin 1 mrna expression via an erK1/2-dependent mechanism. Furthermore, nPB stimulated insulin secretion from inS-1e cells and rat pancreatic islets. By contrast, nPB failed to affect inS-1e cell growth or death. We conclude that nPB may regulate insulin secretion and expression in inS-1e cells and insulin secretion in rat pancreatic islets.

Neuropeptide B promotes proliferation and differentiation of rat brown primary preadipocytes

“…In this context, it is important to point out that contradictory observations were reported regarding the effects of NPB on cell replication and cell death. For example, NPB suppresses proliferation of rat calvaria osteoblast-like cells [18] and promoted replication of rat adrenocortical cells [7]; however, no effects on proliferation in rat insulin-producing INS-1E cells were reported [19]. In the present study, we found that NPB promotes both viability and proliferation of brown preadipocytes.…”

“…For example, it was demonstrated that p38 promotes the expression and/or activity of transcription factors such as PGC‐1α, activating transcription factor 2; both of which are of crucial relevance at stimulating UCP1 expression [29]. Importantly, NPB was found to enhance ERK1/2 phosphorylation in INS‐1E cells [19]. Therefore, since NPB is able to increase differentiation of rat preadipocytes into mature adipocytes in our study, we assessed the effects of this peptide on phosphorylation of p38 and ERK1/2.…”

The Role of Peptide Hormones Discovered in the 21st Century in the Regulation of Adipose Tissue Functions

“…Both, NPB and NPW can activate adenylate cyclase/PKA-dependent cascade, however only NPB activates the PLC/PKC-dependent cascade [ 117 ]. NPB can enhance phosphorylation of ERK1/2 MAP kinase in INS-1E cells [ 118 ] and can stimulate p-38 MAP kinase in rat brown preadipocytes [ 119 ].…”

“…Neuropeptide B is widely expressed in the organism, predominantly in the central nervous system [ 106 , 120 , 121 ], as well as in peripheral tissues, such as the gastrointestinal system, heart, ovary, testes, adrenals, pancreatic islets, and fat tissue [ 118 , 121 , 122 , 123 ]. Neuropeptide B was implicated in controlling appetite [ 108 ], inflammatory pain [ 124 ], stress hormone secretion [ 125 ], and the stimulation of aldosterone [ 126 ], insulin [ 118 ], progesterone, and testosterone [ 127 ].…”

The Role of Neuropeptide B and Its Receptors in Controlling Appetite, Metabolism, and Energy Homeostasis

“…It should be pointed out that both types of NPB receptors interact with another ligand, termed neuropeptide W [ 11 , 15 ]. The intracellular signaling of NPBWR1 and NPBWR1 encompasses the modulation of cAMP, calcium, phospholipase C, or MAP kinase signaling [ 10 , 11 , 16 , 17 ]. The expression of NPB and its receptors in the CNS and various peripheral tissues was reported ( Table 1 and Table 2 ).…”