Utilization of acetate in the human forearm during exercise after ethanol ingestion.

The uptake of acetate in the human forearm was studied in five fasting (14 h) subjects during 10-min periods of ergometer work at 7 and 10 kilopond-meters per minute (kpm/min). A constant arterial acetate concentration was established by administration of a small quantity of alcohol (25 g) to the subjects after a control work period. Blood flow was measured by an indicator dilution technique. Acetate uptake varied linearly with the product of arterial acetate concentration and blood flow. Acetate metabolism was calculated to account for about 6.5% of the energy metabolism, assuming complete combustion to carbon dioxide and water. Oxygen uptake and blood flow did not change in the presence of acetate and ethanol. After administration of ethanol the arterial concentrations of FFA and glycerol decreased to about half, whereas the lactate concentration increased to about twice the control values, confirming other reports. Glucose utilization was increased and lactate output decreased during the ethanol periods, presumably a consequence of the changing arterial concentrations and increased insulin level. Measurements of the arterial and venous lactate/pyruvate concentration ratios indicate that the NAD-mediated cytoplasmic redox state in the muscle is not changed in the presence of acetate and ethanol.

Kinetics of glycerol uptake by the perfused rat liver. Membrane transport, phosphorylation and effect on NAD redox level.

The kinetics of glycerol uptake by the perfused rat liver were determined according to a model which includes membrane transport, intracellular phosphorylation and competitive inhibition of glycerol phosphorylation by L-glycerol 3-phosphate. The membrane transport obeys first-order kinetics at concentrations below 10 mM in the affluent medium. The K-m of the glycerol phosphorylation was 10 muM and the K-i of the L-glycerol 3-phosphate inhibition was 50 muM. The maximum activity (V) was 3.70 mumoles/min per g liver wet wt. These results are similar to in vitro kinetics of the glycerol kinase, except that K-i was found to be somewhat lower in the intact organ. At low glycerol concentrations, a steep concentration gradient exists across the liver cell membrane. The increase in the lactate to pyruvate concentration ratio during glycerol metabolism is related to the actual concentration of L-glycerol 3-phosphate, not to the rate of glycerol uptake.

Thyroid hormone-induced changes in gluconeogenesis and ketogenesis in perfused rat liver.

The regulation of ketogenesis and gluconeogenesis was studied in isolated, perfused livers from hyper- and euthyroid rats. Experimental conditions were varied with respect to lactate and fatty acid concentration in the perfusion medium and with respect to the nutritional state of the rats. 1. The rate of uptake of oleate in perfused livers was independent of the thyroid and nutritional states of the animals. 2. In livers from 48-h-fasted rats no difference was found in rates of ketogenesis between the euthyroid and hyperthyroid livers except when 10 mM lactate was present in the perfusate. In recently fed rats the rates of ketogenesis from oleate (1 mM) and endogenous substrates were low in euthyroid livers (0.45 and 0.05 mumol/min per g liver, respectively), while these rates in hyperthyroid livers were (1.333 and 0.136 mumol/min per g liver, respectively). With octanoate as substrate, high rates of ketogenesis were found in recently fed livers from both euthyroid and hyperthyroid rats (1.573 and 1.717 mumol/min per g liver, respectively). 3. Without oleate in the perfusion medium the rate of gluconeogenesis from low (1 mM) lactate concentrations in livers from 48 h-fasted-rats was slightly increased in the hyperthyroid state (0.548 mumol/min per g liver) compared to the euthyroid state (0.408 mumol/min per g liver). When lactate concentration in the perfusion medium was raised to 10 mM the rate of gluconeogenesis was increased 4-fold in the hyperthyroid livers (1.800 mumol/min per g liver) but only 20% in the euthyroid livers (0.490 mumol/min per g liver). The presence of oleate (1 mM) had no effect on the rate of gluconeogenesis from low lactate concentrations in livers form 48-h-fasted animals of either thyroid state. At 10 mM lactate the inclusion of oleate caused a pronounced stimulation of gluconeogenesis in euthyroid livers (from 0.490 to 1.766 mumol/min per g liver) but not in hyperthyroid livers (from 1.800 to 1.973 mumol/min per g liver) so that the difference in the rate of gluconeogenesis between the two thyroid states disappeared. 4. The content of endogenous substrates was measured in liver biopsies taken before perfusion. The glycogen concentration was independent of the thyroid state in 48-h fasted animals. The triglyceride content was independent of the thyroid state in recently fed animals. In recently fed animals the glycogen content was reduced by 90% in hyperthyroid animals, and in 48-h-fasted animals the triglyceride content was reduced by 50% in hyperthyroid animals. 5. The energy cost of gluconeogenesis from lactate appeared to be independent of the thyroid state.

The onset of liver glycogen synthesis in fasted-refed rats. Effects of streptozocin diabetes and of peripheral insulin replacement.

The mechanism of liver glycogen synthesis after refeeding has been investigated in diabetic rats, diabetic insulin-treated rats, and in control rats fasted for 48 h. The accumulation of liver glycogen was the same in diabetic rats and in control rats after 2 h of feeding, but did not proceed any further in the diabetic group during the next 2 h. Insulin-treated diabetic rats synthesized five times more hepatic glycogen than the control rats after 1 h of refeeding, but the amount accumulated at the end of the refeeding period was the same. Feeding resulted in a transient activation of glycogen synthase in untreated as well as in treated diabetic rats. In control rats, however, glycogen synthase was already partially in the active form before access to food, and the onset of glycogen synthesis occurred without further activation of the enzyme. A transient inactivation of phosphorylase was observed in all groups during the meal, but was very slight in the untreated diabetic rats in which phosphorylase a values were already reduced before the access to food. Peripheral glycemia was markedly increased upon refeeding in treated and untreated diabetic rats, but remained normal in control rats. Peripheral insulinemia was increased by feeding in the control rats and remained low in the diabetic rats and high in the insulin-treated diabetic rats. The results indicate that, in normal controls in contrast to diabetic rats, synthase activation is not a prerequisite for the initiation of glycogen synthesis after a meal; phosphorylase inactivation may be of major importance in normal controls, but also appears to play a role in the diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of Hypo-test, a semiquantitative audio urine-glucose analyzer for blind diabetic individuals.

Hypo-test (Hypoguard Ltd., Suffolk, United Kingdom), a new semiquantitative audio urine-glucose analyzer for blind diabetic individuals, was tested for accuracy and reproducibility against a laboratory glucose method, and for ease of operation by two blind diabetic subjects. Hypo-test results were accurate for urine glucose in the range 0-0.75%, but there was a pronounced tendency for results to be too low at higher urine-glucose concentrations. The reproducibility at high urine-glucose concentrations was poor, and the meter was too sensitive to delays or decreases in the prescribed timing procedure. However, the two blind diabetic subjects found the instrument easy to operate.

The absorption of subcutaneously injected short-acting soluble insulin: influence of injection technique and concentration.

The effect of injection technique on the absorption of subcutaneously injected short-acting insulin [125I-labeled Actrapid (MC), Novo, Copenhagen, Denmark] was investigated in insulin-dependent diabetic patients. In one side of the abdomen insulin was given with a fixed standard technique. In the other side of the abdomen the temperature of the injected insulin, the depth of injection, and the duration of injection were varied. Furthermore, we compared the absorption of U40 and U100 insulin by giving either 8 U of the two insulins or 0.1 ml of both insulins simultaneously to the patients in either side of the abdomen. With regard to the injection technique the only significant finding was a faster absorption rate with deep (12 mm) than with superficial (3 mm) injection. The absorption of U100 insulin was significantly slower than of U40 insulin, when given in the same amount (8 U) as well as in the same volume (0.1 ml).

Self-monitoring of blood glucose without a meter.

We studied the reliability of the Chemstrip system in the self-monitoring of blood glucose by diabetic patients. A total of 453 blood glucose values obtained by 38 diabetic patients using Chemstrip were compared with the glucose values of the same blood samples measured with a conventional laboratory method. We found a definite tendency at concentrations less than 320 mg/dl for patient-read Chemstrip values to be too low. Also, we found a wide range in laboratory values corresponding to a given patient-read Chemstrip value. However, a better agreement between Chemstrip and laboratory values was obtained when the Chemstrips were read by trained staff. We recommend, therefore, that the use of Chemstrip in the self-monitoring of blood glucose can be restricted to patients who have shown competence in the use of Chemstrip during prior testing.

Hypoglycemia and hemostatic parameters in juvenile-onset diabetes.

Hypoglycemia was induced by intravenous infusion of insulin in six juvenile-onset diabetic subjects. Hemostatic parameters were assessed before insulin infusion and 0, 1, and 2 h after discontinuation of insulin infusion. The onset of hypoglycemia coincided with an enhancement of ADP-induced platelet aggregation in five of the patients; platelet aggregation returned to normal levels during the next 2 h. The recalcification time was significantly shortened at the onset of hypoglycemia and continued to decrease for the next 2 h despite the return of serum glucose to normal levels. Correspondingly, a significant increase in fibrinogen was found. The ethanol gelation test was positive in two patients 2 h after stopping insulin infusion. Platelet counts decreased significantly after stopping insulin infusion. Thus, insulin-induced hypoglycemia markedly affects hemostatic balance and may potentially lead to intravascular coagulation in juvenile-onset diabetic patients.

No response of pancreatic hormones to hypoglycemia in diabetic autonomic neuropathy.

The responses of pancreatic hormones (i.e. glucagon, pancreatic polypeptide, and somatostatin) to insulin-induced hypoglycemia were investigated in 18 insulin-dependent diabetics without residual beta-cell function and in 6 normal subjects. Nine of the diabetics had autonomic neuropathy, and 9 had no neuropathy. After hypoglycemia, no significant increase in any of the 3 pancreatic hormones was found in the diabetics with autonomic neuropathy, whereas significant increments were found in the diabetics without neuropathy and in the normal subjects. These results suggest that autonomic nervous activity is of major importance for pancreatic hormone release during hypoglycemia in man.

Diminished immunoreactive gastric inhibitory polypeptide response to a meal in newly diagnosed type I (insulin-dependent) diabetics.

The release of immunoreactive gastric inhibitory polypeptide (IR-GIP) in response to a standard meal was examined in 10 normal subjects and 15 type I (insulin-dependent) diabetics 7 days (test I), 14 days (test II), and 3 months (test III) after time of diagnosis. During all three tests, the diabetics had significantly lower plasma IR-GIP concentrations than the controls from 15-90 min after the standard meal. The IR-GIP response in the diabetics measured as the integrated area under the response curve corresponded to 70% of that of normal subjects. beta-cell function evaluated from the C-peptide response to the meal increased significantly from test I to test III whereas the IR-GIP response was similar during all three tests. As GIP is known to potentiate glucose-induced insulin secretion and possibly the biosynthesis of insulin, the low IR-GIP responses in subjects with type I diabetes may significantly influence insulin levels and hyperglycemia.

Combined adrenal myelolipoma and adenoma associated with Cushing's syndrome.

A case of Cushing's syndrome in a 31-year-old woman is presented. The resected left adrenal gland revealed a tumor consisting of cortical cells intermingled with myelolipomatous tissue comparable to that of normal bone marrow. The adjacent cortex was atrophic. Postoperative plasma cortisol concentrations have remained quite low. Previously, 28 cases of surgically removed adrenocortical tumors with a main diagnosis of myelolipoma have been published. Of these, three cases (two pituitary Cushing's disease, one steroid 21-hydroxylase deficiency) were associated with endocrine dysfunction. The combination of a myelolipoma and a true adenoma has only been described once before (in a case of virilization) and never in connection with Cushing's syndrome. The etiology of myelolipoma is discussed, and a local trigger mechanism related to adrenocortical growth disturbances is suggested.

[Adrenal cortex function in patients with AIDS and healthy HIV-positive persons]. / Binyrebarkfunktionen hos AIDS-patienter og raske HIV1-positive personer.

Adrenal function was estimated by synthetic ACTH test in 18 men with AIDS (or AIDS-related complex) and compared with that of 10 HIV positive but otherwise healthy men. According to this test none fulfilled the criteria for adrenal insufficiency defined as plasma cortisol concentration less than 500 nmol/l 30 minutes after ACTH stimulation. Seven of eighteen AIDS patients had baseline cortisol concentrations above 0.5 mumol/l compared to none in the HIV-positive group. Three of eighteen AIDS patients had a limited response to synthetic ACTH injection compared to none in the HIV-positive group. Two of these three AIDS patients had lowered serum Na+ concentration; they survived for two and three weeks, respectively. Otherwise the basal cortisol level and response to synthetic ACTH was uncorrelated with survival time, other signs of adrenal insufficiency, treatment with ketokonazole, CMV-infection, T-helper cell count or Th/Ts-ratio. The pituitary-adrenal axis was estimated by measuring the diurnal rhythm of serum ACTH and cortisol in eight patients and was found intact and normal in all of them. Thus, absolute adrenal insufficiency is uncommon in AIDS-patients. Relative adrenal insufficiency may occur in severely ill preterminal patients as a result of primary target organ failure, but the pituitary-adrenal axis generally appears to be undisturbed.