Session 1: Regulation of digestive events

Dr C.H. Malbert, Dr T. Studzinski
1999 Reproduction nutrition development (Print)  
tat1on de recherches avicoles, Inra, Tours, 373s(J Nouzilly, France) Upon insulin binding and its autophosphorylation, the insulin receptor (IR) phosphorylates various endogenous substrates such as IRS-1 (Insulin Receptor Substrate-1) and SHC (Src Homology and Collagen protein). IRS-1 (180 kDa) is considered as the major IR substrate in mammalian species. The tyrosine phosphorylation on specific motifs (YXXM, YMXM), allows IRS-1 to interact with several proteins through their SH2 domains such
more » ... SH2 domains such as PI-3 kinase, Grb2, SHPTP2. In mammals, SHC (66, 52 and 46 kDa) are encoded by the same gene. IRS-1 and SHC are involved in metabolic and mitogenic effects of the IR. We have recently partially or totally cloned and sequenced the coding region of chicken SHC and IRS-1, respectively. These genes are highly conserved when compared to mammals. In the present study, we have characterized and studied the expression and tyrosine phosphorylation of IRS-1 and SHC in vivo in chicken muscle and liver. Thirty 9-week-old chickens were subjected to three nutritional states (ad libitum, fasted for 48 h, and refed for 30 min after 48 h fast). By using differential immunoprecipitation of liver and muscle materials with specific antibodies directed against SHC or IRS-1, we have demonstrated that these two substrates are expressed in chicken. We have also shown that IRS-1 and mainly the 52-kDa SHC isoform are associated to the IR. The levels of tyrosine phosphorylation of IRS-1 and SHC are dependent upon the nutritional state with a decrease in phosphorylation in the fasted state which is restored after 30 min of refeeding. Their phosphorylation is well correlated with plasma insulin levels. Finally, IRS-1 and SHC mRNA levels have been examined in the three nutritional states using RT-PCR techniques. Fasting increased IRS-1 mRNA expression in the liver but not in the muscle. In conclusion, SHC and IRS-1 are expressed and associated with IR in chicken liver and muscle. Their tyrosine phosphorylation is regulated by the nutritional state. It is now impossible to differentiate the age versus diet related influences on digestive secretions. The MMC pattern quantitatively and qualitatively modulates pancreatic secretion in calves. Histamine increases pancreatic secretion primarily via H2 and partially via H1 receptor activation. The role of physiological histamine needs to be further defined. CCKB receptors present on the acini themselves modulate acini secretion in the absence of intrinsic or extrinsic regulatory pathways. CCKA receptor activation partially determines postnatal small intestine mucosal development in calves. Nitrates may change the myoelectric activity of the fed rat stomach. More data are needed in order to clarify their effect in the fasted state. Starch is an excellent example of a nutrient that requires a careful ratio between degradability and digestion capacity for optimal utilisation.
doi:10.1051/rnd:19990139 fatcat:mvcsso2fmnbnla5dpwl7ym6pcu