Selenium supplements increased the circulating Se levels. Supplementation was associated with modest changes in thyroid hormones, with an earlier normalisation of T4 and reverse T3 plasma levels. The addition of AT and zinc did not produce any additional change.

Type I diabetic patients with impaired kidney function are at an excessively high risk of severe hypoglycemia. In addition to low HbA1c levels, a low body mass index appears to be a risk indicator for this adverse effect of insulin therapy.

Non-glucoregulatory hormones (T4, T3, rT3, TSH and testosterone) were studied by radioimmunoassay in juvenile-type diabetics in moderate control and in ketosis due to insulin withdrawal and in age matched "normals" during a mild prolonged exercise test. The basal serum hormone levels revealed the following findings: Serum testosterone was markedly lower in diabetics than in normals ( 177 +/- 24 resp. 618 +/- 52 ng/dl). This is in contrast to other studies, but it may reflect decreased testicular function due to an early, clinically not apparent atherosclerotic disease. Serum T3 was significantly lower in diabetics than in normals (110 +/- 16 resp. 145 +/- 19), suggesting an early "low T3-syndrome" in juvenile-type diabetics. However, increased serum rT3 levels were not observed, and serum T4 and TSH were normal. Mild prolonged exercise had no major effects on these nonglucoregulatory hormones. In juvenile-type diabetics the degree of metabolic control had no influence on the response of the mentioned hormones. However, an increased cortisol/testosterone ratio in ketotic diabetics in the basal state with a further increase during exercise was demonstrated, indicating an aggravation of the catabolic state in these patients during exercise.

D uring a fast, fatty acids and later ketone bodies readily replace glucose as a fuel for muscle. 1~4 This switch in muscle fuels is one of-the first steps man takes to restrict the unnecessary use of carbohydrates and thereby limit the need for gluconeogenesis from protein when he is deprived of food. Although diminished circulating levels of insulin and glucose undoubtedly contribute to these changes, other mechanisms such as diminished insulin sensitivity and inhibition of glucose metabolism by lipid substrates may also play a role. 5 " 7 In order to study this problem, we have evaluated some of the factors governing the metabolism of glucose in skeletal muscle using the isolated perfused rat hindquarter preparation. This report deals with the effects of starvation, moderately severe diabetes, and acetoacetate on glucose uptake and disposition in resting and exercising muscle. METHODSThe hindquarter preparation used has been described previously. 8 In essence, the tissue of the lower third of an anesthetized rat is perfused through a cannula inserted into the aorta, and perfusate leaving the preparation exits through a cannula in the vena cava. To make the hindquarter as much as possible a muscle preparation, skin and superficial adipose tissue are removed and abdominal branches of the great vessels that do not supply muscle are ligated.The perfusion medium is composed of Krebs-Henseleit solution and contains aged human red cells (7-8 g/100 ml), 4% albumin, 5 mM glucose, and lactate and pyruvate at physiologic concentrations. Throughout the perfusion, it is gassed with 95% O 2 -5% CO 2 ; flow to the preparation is maintained at a rate of 11 ml/min. We have replaced the bulb oxygenator utilized in early experiments with a silastic coil in order to eliminate the need for a second passage of medium through the pump and thereby to diminish hemolysis. Flow rate with this system is 12-13 ml/min. This has not appeared to alter the metabolism of the preparation. On the other hand, as hemolyzed red cells degrade insulin, 9 -93 it has made experiments at low concentrations of insulin more feasible (see below).The isolated perfused hindquarter offers several advantages over many earlier skeletal muscle preparations; the tissue receives exogenous substrates and O 2 through the usual vascular channels, normal anatomical relationships to bone and nerve are maintained, and the muscle can be made to exercise by sciatic nerve stimulation. A comparison of the metabolic characteristics of the perfused hindquarter and hindquarter muscle of an intact rat is shown in Table 1. RESULTS Glucose utilization.It is not clear whether during starvation the utilization of glucose by skeletal muscle is diminished by factors other than the decreases in plasma insulin and glucose. We have previously shown that the stimulation of glucose uptake by insulin is not depressed in hindquarters of starved rats; however, supraphysiologic concentrations of insulin were used. 11 To explore the possibility that glucose utilization might be diminished ...

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