Search

To clearly understand the hyperglycemic action of glucocorticoids, we studied the action of glucagon on lactate gluconeogenesis in the liver of rats 7 days after adrenalectomy and after treatment with 1 mg/kg dexamethasone for 7 days. The liver was isolated and cyclically perfused at 20 ml/min with 25 ml of perfusion medium containing 5 mM lactate, [U-14C]lactate, and 0-100 ng/ml glucagon. In the absence of glucagon, incorporation of [14C]lactate into glucose carbon 1 did not change significantly in the adrenalectomized rat liver (1.66 +/- 0.12% of total radioactivity for 5 min) and increased in the dexamethasone-treated rat liver (3. 61 +/- 0.54%, P0.01) compared to the normal rat liver (1.99 +/- 0. 28%). The response of lactate gluconeogenesis to glucagon was extremely blunted in the adrenalectomized rat liver and was much larger in the dexamethasone-treated rat than in the normal rat liver (at a glucagon concentration of 100 ng/ml, 2.13 +/- 0.33, 8.55 +/- 1. 06, and 4.61 +/- 0.53% for 5 min, respectively). Glucagon binding to liver plasma membrane was not changed by adrenalectomy and was decreased by dexamethasone treatment. These results suggest that glucocorticoids induce hyperglycemia by increasing the response to glucagon, together with the high basal activity of hepatic gluconeogenesis. In addition, these effects do not occur through changes in glucagon binding to receptors.

The bihormonal control by insulin and glucagon of blood ketone body level was studied. Mixed solutions with various molar ratios of glucagon and insulin (G/I) were subcutaneously infused continuously for five days by use of the osmotic minipump in the normal rats. The concentrations of insulin and glucagon solution were set at the high G/I molar ratio, the moderate G/I molar ratio and the low G/I molar ratio. In addition, the moderate G/I molar ratio group was divided into three sub-groups: low glucagon and low insulin, moderate glucagon and moderate insulin, and high glucagon and high insulin. After five days, the rats were decapitated to measure plasma ketone body, free fatty acid (FFA), glucose, insulin and glucagon. The FFA level was not significantly different among three groups. The glucose level was not different between the high and moderate G/I molar ratio groups, and decreased in the low G/I molar ratio group. 3-beta-hydroxybutyrate (3-OHBA) and acetoacetate (AcAc) levels in the high G/I molar ratio group were elevated, and 3-OHBA level in the low G/I molar ratio group was lowered compared to those in the moderate G/I molar ratio group. Among three moderate G/I molar ratio sub-groups, there was no difference in 3-OHBA and AcAc levels. These results demonstrate that plasma ketone body levels are controlled by the plasma G/I molar ratio.

To study effects of the portal-arterial glucose difference on the hepatic glycogenesis, the liver was isolated from fasted rats and was bivascularly perfused. Thirty-five milliliters of Krebs-Ringer buffer (pH 7.4) with 2 mM glucose, 3 mM lactate, 20 ng/ml insulin, and [1-14C]glucose or [U-14C]lactate was recirculated at flow rates of 14 ml/min via the portal vein and 7 ml/min via the hepatic artery. Glucose was continuously infused at a rate of 27.75 mumol/min into the portal (P experiment) and the arterial cannula (A experiment), and the portal-arterial glucose gradients were +1.98 and -3.96 mM. Perfusate glucose concentration was not different between the P and A experiments within 20 min. Perfusate lactate level was higher in the P experiment than in the A experiment at 20 min. Incorporation of radioactivity from [14C]glucose into glycogen was higher in the P experiment than in the A experiment (0.245 +/- 0.014%/20 min vs 0.175 +/- 0.022%/20 min, P0.01), and not influenced by the addition of insulin. Incorporation of 14C from [14C]lactate into glycogen was not different between the P and A experiments, and was significantly increased with the addition of insulin. This activity, in the presence of insulin, was higher in the P experiment than in the A experiment (0.490 +/- 0.028%/20 min vs 0.406 +/- 0.025%/20 min, P0.05). These results suggest that the portal-arterial glucose difference has an important role in the regulation of hepatic glycogenesis from exogenous glucose and gluconeogenesis.

INTRODUCTION found on his back. The hemoglobin level was 13.8 g/ dL, leukocyte count was 392/mL, and no abnormal About 60% of patients with acquired immunodeparameters of the renal and liver functions were found ficiency syndrome (AIDS) develop phenuexcept for 840 IU (normal, 140–360 IU) of lactic dehymocystis pneumonia.1 The present drugs drogenase (LDH). In addition, Human Immunodefiof choice include sulfamethoxazole/triciency Virus (HIV) antibodies were found, and the methoprim and pentamidine. Pentamidine-induced CD4/CD8 lymphocyte ratio was 0.05 (CD4 8 cells/mL, diabetes mellitus is a serious side effect. Plasma tumor CD8 165 cells/mL). On breathing room air, the patient necrosis factor a (TNF-a) increases in some AIDS pashowed severe hypoxemia (PaO2 46.5 Torr) with low tients.2 TNF-a is associated with the insulin resistance3 PaCO2 (27.2 Torr). Chest X-ray revealed bilateral difand pancreatic b cell dysfunction.4 We report one pafuse alveolar infiltrates. A bronchoalveolar lavage was tient with a very high level of plasma TNF-a who performed on hospital day 1, and the sample demonacquired diabetes mellitus following pentamidine strated the presence of Pneumocystis carini (silver treatment for pneumocystis pneumoniae. stain). He was treated with intravenous pentamidine isethionate 150 mg/day (3 mg/kg) and peroral sulfamethoxazole/trimethoprim (8 g/day). On hospital day CASE REPORT 11, plasma glucose was 80 mg/dL after breakfast. On A 29-year-old heterosexual man with a 4-week history hospital day 30, he had complaints of thirst, polydipsia, of fever, dyspnea, and productive cough was admitted and polyuria. Fasting plasma glucose was 1440 mg/ to our hospital. He had no previous history of any dl. Other laboratory data in this point showed urinary serious disease and no family member with diabetes glucose 41, urinary ketone 1, serum insulin 6 mU/ mellitus. He was found to have fever (37.48C), tachycarmL, serum C-peptide 1.5 ng/mL, serum ICA antibody dia (90 beats/min), tachypnea (30 breaths/min), and negative, serum GAD antibody negative, TNF-a 220 cyanosis. Chest auscultation revealed Velcro rales in pg/mL (normal LT 6) and IL-6 44 pg/mL (normal LT the bilateral lower lung area. Kaposi’s sarcoma was 25). The treatment of sulfamethoxazole/trimethoprim and pentamidine isethionate was discontinued. The patient received intravenous fluid hydration and regu