Hepatic Balances of Glucose and Insulin in Response to Physiological Increments of Endogenous Insulin during Glucose Infusions in Dogs

Abstract. Hepatic glucose uptake was measured in dogs in relation to physiological increments of plasma insulin levels under steady state conditions. Endogenous insulin secretion was stimulated by the infusion of small glucose loads, achieving normoglycaemia or mild hyperglycaemia. The measurement of hepatic arterial and portal venous blood flows allowed calculation of the relationships between net hepatic balances of insulin and glucose, the magnitude of insulin extraction by the liver and the hepatic sensitivity to physiological levels of insulin. During normoglycaemia, small glucose loads (2 and 4.5 mg/min. kg) reduced hepatic glucose output without a concomitant increase of the estimated total glucose utilization. No changes in arterial or hepatic venous plasma insulin levels occurred. Portal venous plasma insulin alone rose under the influence of the glucose stimulus. In the presence of hyperglycaemia, the liver further reduced its glucose output. Infusions of 11.3 mg/min. kg glucose resulted in reversal of hepatic glucose output to a net uptake of glucose. However, due to the large amounts of insulin emerging from the liver, peripheral tissue glucose utilization was significantly increased. A strong inverse correlation existed between arterial glucose concentration and hepatic glucose output as well as between portal venous plasma insulin level and hepatic glucose output. The net hepatic balance of insulin was promptly raised in response to the glucose perfusions, even when normoglycaemia was maintained. A highly significant, inverse correlation was demonstrated between net hepatic balance of insulin (i.e. net uptake of insulin by the liver) and hepatic glucose output. Hepatic insulin extraction ratio and hepatic plasma insulin clearance increased during glucose administration but no evident relationship to portal venous plasma insulin levels was found. These data suggest that insulin rather than glucose is the primary agent responsible for the reversal of the hepatic gradient of glucose in vivo.

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