Glycogen synthesis in the perfused liver of streptozotocin-diabetic rats.
1. Net glycogen accumulation was measured in sequentially removed samples during perfusion of the liver of starved streptozotocin-diabetic rats, and shown to be significantly impaired, compared with rates in normal (starved) rats. 2. In perfusions of normal livers with glucose plus C3 substrates, there was an increase in the proportion of glycogen synthetase 'a', compared with that in the absence of substrates. This response to substrates, followed in sequential synthesis and enzymic sensitivity in the perfused liver of diabetic rats were reversed by pretreatment in vivo with glucose plus fructose, or insulin. Glucose alone did not produce this effect. 4. Glucose, fructose, insulin or cortisol added to e perfusion medium (in the absence of pretreatment in vivo) did not stimulate glycogen synthesis in diabetic rats. 5. In intact diabetic rats, there was a decline in rates of net hepatic glycogen accumulation, and the response of glycogen synthetase to substrates. The most rapid rates of synthesis were obtained after fructose administration. 6. These results demonstrate that there is a marked inherent impairment in hepatic glycogen synthesis in starved diabetic rats, which can be rapidly reversed in vivo but no in perfusion. Thus hepatic glycogen synthesis does not appear to be sensitive to either the short-term direct action of insulin (added alone to perfusions) of to long-term insulin deprivation in vivo. The regulatory roles of substrates, insulin and glycogen synthetase in hepatic glycogen accumulation are discussed.
D000818:Animals; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000378:metabolism*; D005632:Fructose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D005958:Glucosephosphates / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D010477:Perfusion; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D013217:Starvation; D013311:Streptozocin; D014532:Uridine Diphosphate Glucose / Q000378:metabolism; D014539:Uridine Diphosphate Sugars
D005958:Glucosephosphates; D008112:Liver Glycogen; D014539:Uridine Diphosphate Sugars; D005632:Fructose; D013311:Streptozocin; D006005:Phosphorylases; D006006:Glycogen Synthase; D005947:Glucose; D014532:Uridine Diphosphate Glucose