Abstract

To quantify the extent to which exogenous glucose is used directly or indirectly for hepatic glycogen synthesis, fasted rats were given [U-14C,3-3H] glucose intragastrically, intravenously, or as a component of a solid diet eaten ad libitum. In all cases liver glycogen was deposited at high linear rates over a 3-h period. Portal vein glucose levels seldom exceeded 8 mM. At a time when the specific activities of 3H and 14C in circulating glucose were identical with those in the administered material their values in newly synthesized glycogen were reduced by 72-88% and 50-65%, respectively. An intragastric load of unlabeled glucose sufficient to suppress completely hepatic glucose output greatly stimulated the incorporation of intravenously infused [14C]bicarbonate, [14C]lactate, [14C]alanine, and [14C] glutamine into liver glycogen. Using an improved assay the ability of liver homogenates to phosphorylate glucose at concentrations of 5-10 mM was found to be far short of what would be needed if glucose were used directly to support hepatic glycogen synthesis in vivo. These data support the notion that in the rat a major fraction of liver glycogen deposited in response to exogenous carbohydrate is formed by a pathway involving glucose leads to C3 unit leads to glycogen, although the site of the initial steps in the sequence is not yet known. The limited capacity of the liver to utilize intact glucose for glycogen synthesis might reside in its limited capacity to phosphorylate the sugar at physiological concentrations.

Highlights

  • T Oquantify the extentto which exogenous glucoseis be obtained when the liver preparations were presented with used directly or indirectlfyor hepatic glycogensynthe- a mixture of glucose, gluconeogenic precursors, and certain sis, fasted rats were given [U-’4C,3-3H] glucoseintra- amino acids

  • An intragastric load of unlabeled glucose sufficient to suppress completely hepatic glucose output greatly suggested that following the absorption of glucose a product of its metabolism might serve as the major substrate for glycogen synthesis in the liver, the conversion of triose toglycogen being permissivelystimulated by an elevated blood glucose level (6)

  • 5-10 mM was found to be far short of what would be carbohydrate metabolism.,using the rat as the needed if glucose were used directly to support hepatic experimental model we sought answers to thfeollowing quesglycogen synthesis in vivo

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Summary

RESULTS

Fasted rats received [U-14C,3-3H]glucose (2.a5nd 1pCi per mmol, respectively) intravenously a t a rate of 334 mg/100 g body weight/h as described under "Experimental Procedures." Values are means f. Fasted rats were allowed to eat ad libitum a powdered diet (40% glucose containing [U-'4C,3-3H]glucose(2.5 and 1 pCi per mmol, respectively) as described under "Experimental Procedures." Values are means f S.E. for the number of animals shown. Takentogether,thedata of Tables 1-111 indicatedthat regardless of the route by which the animals received exogenous carbohydrate only 12-28% of the glycogen deposited in TABLEIV liver could have been formed from the direct incorporationof circulating glucose Fasted rats received [U-"Cllactate (3 PCi per mmol) intravenously at a rate of 57 mg/100 g body weight/h together with wateror unlabeled glucose (167 mg/100 g body weight/h) intragastrically as described under"ExperimentalProcedures."Values are means f S.E. for the number of animals shown in parentheses

Liver glycogen
Glucose Glucose
Glycogen Synthesis in the Rat
Glucose phosphorylated
Findings
The central role of the mammalian liver in glucose homemin
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