Importance of glucagon for nitrogen loss in diabetes--via an accelerated hepatic conversion of amino nitrogen to urea nitrogen.
In diabetes mellitus amino nitrogen is lost from organs and excreted as urea. Traditionally it has been assumed that the only explanation of this phenomenon was lack of insulin. The blood amino acid concentration in diabetic patients is, however, reduced, which suggests that the hepatic uptake of amino acids is accelerated. Glucagon accelerates the hepatic uptake and conversion of amino nitrogen into urea nitrogen, and hyperglucagonaemia is present in diabetes. This survey describes the significance of hyperglucagonaemia in the abnormal diabetic nitrogen metabolism. Rats with experimental diabetes and hyperglucagonaemia, given the same amount of food as controls, double the urinary excretion of urea-N within 4 days. This increase can be completely normalized by an intensive insulin treatment regimen, which normalises the hyperglucagonaemia as well. Selective hyperglucagonaemia in otherwise optimally insulin treated diabetic rats raises the urinary urea-N excretion by one third, also within 4 days. The kinetics of urea synthesis in experimental diabetes is changed towards an increased maximum rate, but only after 14 days, so this alone cannot explain the increased urea excretion. Constant hyperglucagonaemia increases the spontaneous rate of urea synthesis within 2 days. In uncontrolled diabetes nitrogen is lost from most organs, and most is lost from muscles. Selective hyperglucagonaemia in insulin treated diabetic rats leads to a loss of muscle nitrogen of about one third of that seen in uncontrolled diabetes. It is suggested that he glucagon induced loss of muscle nitrogen is due to an increased flux of amino nitrogen from muscle to liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Almdal
T P
TP
Medical Department A, Rigshospitalet, Copenhagen.
D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D014508:Urea / Q000378:metabolism*
D014508:Urea; D005934:Glucagon; D009584:Nitrogen