Although adrenalectomy is usually associated with an impairment of ammonium and/or titratable acid excretion by the kidney, it is uncertain whether rates of renal net acid excretion are also reduced. Further, it is unclear whether the absence of the adrenal gland itself or other factors of adrenal insufficiency mediate such changes in renal acidification parameters. For example, dramatic increases in ammonium excretion can accompany correction of the hyperkalemia seen in adrenal insufficiency. There is also evidence that reduced rates of acid excretion can result from changes in food intake, urine flow rate, urine pH or distal sodium delivery rates. With these considerations in mind, we undertook studies to isolate the chronic effects of adrenalectomy on renal net acid excretion rates in the unanaesthetized rat. To avoid supranormal potassium stores, we gave the adrenalectomized animals potassium-restricted diets. In balance studies, urine flow rates, urine pH, food intake, and distal sodium delivery rates were all successfully controlled for 13 days by pair feeding and by appropriately changing the sodium and potassium contents of diets. Adrenalectomized rats excreted less net acid than did control animals with or without ammonium chloride loading. Further, the severe metabolic acidosis associated with ammonium chloride loading was clearly mitigated by steroid replacement. Accordingly, we conclude that the adrenal gland is essential for normal renal net acid excretion.

The plasma concentration of glucagon (IRG), catecholamines, and hepatic glucose production (Ra) were followed in insulin-induced hypoglycemia in dogs before (normal) and at 14-21 and again at 89-119 days after the injection of alloxan (diabetic). Some diabetic dogs were also tested when euglycemia was restored by phlorizin. In the normal state plasma IRG and epinephrine were raised by a factor of 3 and 15, respectively. Ra increased in two phases, an early peak (350% basal) was followed by a plataeu at about twice basal. In diabetes, irrespective of its duration, plasma IRG was decreased in hypoglycemia, and the rise in plasma epinephrine was significantly reduced. Ra remained unchanged. In phlorizin-treated euglycemic diabetic dogs plasma IRG fell, and the response in plasma epinephrine remained blunted. There was no early rise in Ra, but the same elevated plateau was reached at the same time as in normal animals. In conclusion, the following is observed in diabetic dogs. 1) The sensitivity of alpha-cells to insulin is maintained, but that to hypoglycemia is lost. The concentration of plasma catecholamines is raised less than in normals. With no increase in plasma glucagon this rise is not sufficient to increase Ra. 2) Restoration of euglycemia with phlorizin does not restore normal IRG and epinephrine responses to hypoglycemia but restores the delayed increase of Ra. Thus the restoration of euglycemia in severely diabetic dogs partially restores the responses of the liver, but not of the alpha-cell or sympathetic discharge, to hypoglycemia.

A B S T R A C T We have carried out perfusion studies on hydropenic and bicarbonate-loaded rats to provide direct in vivo observations on bicarbonate accumulation in the short loops of Henle. Analysis of early distal tubular fluid was made during bicarbonate-free saline perfusion from the end proximal to the early distal site, documenting accumulation of "new" bicarbonate. During perfusion in hydropenic rats, steady-state bicarbonate concentrations were suggested by early distal values of -6 mM, which were independent of perfusion rate and virtually indistinguishable from bicarbonate concentration measured during free flow when filtered bicarbonate was allowed to enter the loop. Thus, loop bicarbonate accumulation was apparently sufficient to allow new bicarbonate to enter at a rate comparable to that delivered to the early distal site during free flow, recognizing of course that free-flow delivery rates are the result of complex components of filtration and bidirectional fluxes. In bicarbonate-loaded rats, however, bicarbonate accumulation rates although higher than in hydropenia, were much lower than free-flow delivery rates. Furthermore, early distal bicarbonate concentrations during bicarbonate loading fell as perfusion rate increased, presumably because of a limitation to increasing ionic bicarbonate entry.

Potassium influx in short loops of Henle was assessed using end proximal to early distal perfusion with potassium-free saline. Over a wide range of perfusion rates influx was highly correlated with collected flow rates. The magnitude of the influx was comparable with the delivery rate of potassium to the early distal site seen during free flow, over a narrower range of collected flow rates.

Previous investigations have demonstrated that acetone is a true, if minor precursor of glucose in vivo. In diabetic rats 1.30% of the carbon atoms of circulating glucose arises from acetone, whereas 0.67% does in normal 3-day fasted animals. Calculated from these fractions and the turnover rate of glucose, 48 micrograms/kg. min acetone-carbon is converted to glucose-carbon in diabetic and 16 micrograms/kg. min in normal rats. In both groups of rats the labelling of plasma lactate was stronger than that of glucose. In view of these results we conclude that: the transfer of C-atoms from acetone to glucose increases in diabetes; acetone remains a minor source of glucose even in ketonemic diabetic rats.