Conlon J M, Youson J H, Mommsen T P
Department of Biomedical Sciences, Creighton University Medical School, Omaha, NE 68178.
Biochem J. 1993 Nov 1;295 ( Pt 3)(Pt 3):857-61. doi: 10.1042/bj2950857.
The bowfin, Amia calva (order Amiiformes) occupies an important position in phylogeny as a surviving representative of a group of primitive ray-finned fishes from which the present-day teleosts may have evolved. Glucagon and glucagon-like peptide (GLP) were isolated from an extract of bowfin pancreas and their primary structures determined. Bowfin glucagon shows only four amino acid substitutions compared with human glucagon, and bowfin glucagon was equipotent and equally effective as human glucagon in stimulation of glycogenolysis in dispersed hepatocytes from a teleost fish, the copper rockfish, Sebastes caurinus. In contrast, bowfin GLP shows 15 amino acid substitutions and three amino acid deletions compared with the corresponding region of human GLP-1-(7-37)-peptide. In particular, the bowfin peptide contains an N-terminal tyrosine residue rather than the N-terminal histidine residue found in all other glucagon-related peptides so far characterized. Bowfin GLP stimulated glycogenolysis in rockfish hepatocytes, but was 3-fold less effective and 23-fold less potent than human GLP-1-(7-37)-peptide. We speculate that selective mutations in the GLP domain of bowfin preproglucagon may be an adaptive response to the previously demonstrated low biological potency of bowfin insulin.
弓鳍鱼，即雀鳝（弓鳍鱼目），作为一群原始硬骨鱼的现存代表，在系统发育中占据重要地位，现代硬骨鱼可能是由这群原始硬骨鱼进化而来的。从弓鳍鱼胰腺提取物中分离出了胰高血糖素和胰高血糖素样肽（GLP），并确定了它们的一级结构。与人类胰高血糖素相比，弓鳍鱼胰高血糖素仅显示四个氨基酸替换，并且在刺激硬骨鱼铜岩鱼（Sebastes caurinus）分散肝细胞中的糖原分解方面，弓鳍鱼胰高血糖素与人类胰高血糖素具有同等效力且同样有效。相比之下，与人类GLP-1-(7-37)-肽的相应区域相比，弓鳍鱼GLP显示15个氨基酸替换和3个氨基酸缺失。特别是，弓鳍鱼肽含有一个N端酪氨酸残基，而不是迄今为止所有其他已鉴定的胰高血糖素相关肽中发现的N端组氨酸残基。弓鳍鱼GLP刺激了岩鱼肝细胞中的糖原分解，但效力比人类GLP-1-(7-37)-肽低3倍，效能低23倍。我们推测，弓鳍鱼前胰高血糖素GLP结构域中的选择性突变可能是对先前证明的弓鳍鱼胰岛素低生物活性的一种适应性反应。
