Total forearm glucose utilization (FGU) was determined during 100 gm. oral glucose tolerance tests (GTT) in twenty-five normal volunteers. In addition, the concomitant balance of insulin, growth hormone, and lactate across the forearm was studied in thirteen subjects. The increment in FGU during the three hours following glucose ingestion amounted to 74 mg./100 ml. forearm; it may be calculated that increased peripheral glucose utilization accounted for the disposal of 42 per cent of the 100 gm. load and that during the GTT some 58 gm. of extra glucose reached the peripheral circulation. Serum insulin concentrations in mixed venous (MY) blood rose steeply after glucose loading, while growth hormone levels were reduced. Additional observations in thirteen subjects showed that MV insulin levels remained significantly lower than corresponding arterialized venous (AV) concentrations between thirty and 150 minutes, suggesting that insulin was being continually removed bythe forearm tissues during this time. Significant AV-MV differences were not detected in growth hormone levels. Plasma lactate concentrations rose immediately after glucose loading, reaching a peak at sixty minutes and declining thereafter. The initial elevation was associated with lactate uptake by the forearm and the subsequent fall with lactate release, suggesting that peripheral lactate metabolism has little or no influence on the shape of the lactate response curve. It is suggested thatthis early rise in lactate concentrations is the result of increased hepatic lactate production and that the timing and height of the lactate peak reflect the pattern of enhanced hepatic glucoseutilization after oral glucose loading. Our results suggest that the disposition of a 100 gm. oral glucose load is accounted for mainly by hepatic glucose conservation rather than peripheral uptake and, therefore, that the former is the major determinant of the shape of the oral glucose tolerance curve.

The relationship between the basal glucose concentration, glucose tolerance and peripheral glucose uptake has been studied in nonobese diabetic males not requiring insulin by determining forearm glucose uptake (FCU) during a 100 gm. oral glucose tolerance test (GTT) before and after carbohydrate restriction. On a normal diet basal glucose concentrations were elevated and glucose tolerance was grossly impaired; the increment in FCU during the CTT (0 to 180 minutes) amounted to 52.8 mg./100 ml. forearm. After carbohydrate restriction basal glucose concentrations were reduced, the glucose tolerance curve was lowered and the increment in FCU rose to 76.5 mg./100 ml. forearm; glucose tolerance, however, expressed as the incremental area under the glucose tolerance curve (0 to 180 minutes), remained unchanged. Serum insulin responses during the tests were low and uninfluenced by carbohydrate restriction. Blood lactate concentrations were increased by glucose loading before but not after carbohydrate restriction. FFA and β-hydroxybutyrate concentrations fell progressively after glucose loading while, conversely, acetoacetate concentrations were initially unchanged. During the GTT acetoacetate was taken up by the forearm while lactate and β-hydroxybutyrate were released. In addition, the responses of three diabetics on a normal diet were compared with those of age-matched normal men; in each diabetic FGU was equal to or greater than that in the normal subjects, but nonetheless, the increment in glucose concentrations was several times greater. The results suggest that in these patients with diabetes [1] the lowering of the glucose tolerance curve by carbohydrate restriction is not synonymous with an over-all improvement in tissue glucose disposal but is due primarily to a fall in the basal glucose concentration and [2] the impairment of glucose tolerance both before and after carbohydrate restriction is predominantly the result of a reduction in hepatic rather than peripheral glucose uptake.

Forearm glucose uptake and lactate balance across the forearm were determined in normal subjects during 100-gm. oral glucose tolerance tests (GTT) before and after a lowcarbohydrate diet; in addition, β-hydroxybutyrate and acetoacetateresponses were measured following carbohydrate restriction. After a low-carbohydrate diet, glucose tolerance was significantly impaired (dietary diabetes) and the rise in seruminsulin levels was frequently, but not invariably, delayed. Forearm glucose utilization, however, was not significantly decreased at any phase of the GTT or during the GTT as a whole. With a normal diet, lactate levels rose immediately after glucose loading, reaching peak concentrations at sixty minutes and falling progressively thereafter; this rise was associated with lactate utilization by the forearm and the subsequent fall in plasma concentrations with lactate release. In contrast, following carbohydrate restriction lactate concentrations were initially reduced by glucose administration, this reduction taking place despite continuing lactate release from the forearm. These results suggest that after glucose loading the shape of the lactate response curve is not determined primarily by changes in peripheral lactate balance. Marked elevation in basal FFA, β-hydroxybutyrate, and acetoacetate levels accompanied carbohydrate restriction. FFA and β-hydroxybutyrate concentrations were immediately decreased and acetoacetate levels initially increased by glucose loading, the latter declining only during the second hour of the GTT; throughout the test, acetoacetate was taken up by the forearm while β-hydroxybutyrate was released. Basal FFA and β-hydroxybutyrate concentrations were not correlated with the degree of glucose intolerance induced in the volunteers. The results show that the impairment of glucose tolerance following carbohydrate restriction is not the result of decreased peripheral glucose utilization. It is suggested that the major cause of dietary diabetes is a delay in the hepatic uptake of the glucose load and that this is primarily the. result of low hepatic glucokinase activity rather than delayed insulin secretion.

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