Increased insulin action in cultured hepatocytes from rats with diabetes induced by neonatal streptozotocin.

Previous studies have shown that Wistar rats injected at birth (n0) with STZ (n0-STZ) develop as adults a noninsulin-dependent diabetic state characterized by a lack of insulin response to glucose in vivo, a mild basal hyperglycemia, and an impaired glucose tolerance. Our former in vivo studies using the insulin-glucose clamp technique revealed an increased insulin action upon hepatic glucose production in these animals. We have now cultured hepatocytes from these mildly diabetic rats in parallel with hepatocytes from control rats, to examine more closely basal and insulin-regulated glucose production and glucose incorporation into glycogen.

Plasma atrial natriuretic peptide and vasopressin during thermal dehydration in supine posture.

After 30 minutes spent in an upright posture six healthy male subjects underwent two 130-minute experiments in a supine posture, the first in thermoneutral conditions (TC) and the second, 15 days later, in a hot environment (HE) in order to obtain a water loss of 2.5% body weight. In thermoneutral conditions, the supine posture induced plasma volume expansion, resulting in slightly lowered plasma vasopressin (AVP) levels and higher plasma atrial natriuretic peptide (ANP) levels, compared to the values obtained in the upright posture (P less than 0.

Insulin receptor tyrosine residues 1162 and 1163 control insulin stimulation of myristoyl-diacylglycerol generation and subsequent activation of glucose transport.

Chinese hamster ovary (CHO) transfectants expressing human insulin receptors that were mutated at tyrosines 1162 and 1163 (CHO-Y2 cells) exhibit decreased insulin stimulation of both receptor tyrosine kinase and 2-deoxyglucose uptake compared with transfectants expressing wild-type human insulin receptors (CHO-R cells). We now provide evidence that insulin stimulation of myristoyl-diacylglycerol (DAG) production is also markedly impaired in CHO-Y2 cells; this is manifested as a decreased responsiveness and sensitivity to insulin as compared with CHO-R and parental CHO cells. Further, we report that (i) the concentration-response curves of insulin-stimulated myristoyl-DAG production and 2-deoxyglucose uptake were superimposable within each of the three cell lines.

Comparison of neuroendocrine measurements under laboratory and naturalistic conditions.

Urinary catecholamines and cortisol were measured in healthy nonsmoking white collar workers (14 male and 15 female managers, 15 male and 14 female clerical workers), aged 30-50 years, during a one-hour period of laboratory-induced stress comprising five tests and a Type A interview, and during a subsequent period of rest in the laboratory. Values were compared with data obtained four months earlier from the same subjects during a normal day at work (4 values) and during a work-free day at home (4 values). No significant group differences were found during rest in the laboratory.

Dual effect of metformin in cultured rat hepatocytes: potentiation of insulin action and prevention of insulin-induced resistance.

The ability of the biguanide hypoglycemic agent metformin to improve the acute effects of insulin on glucose and/or lipid metabolism was investigated in both insulin-responsive and insulin-resistant cultured rat hepatocytes: (1) metformin (20 micrograms/mL, 16 hours) increased the insulin-dependent stimulation of glycogen and lipid synthesis through an exclusive enhancement of the responsiveness without modification of the cell sensitivity to the hormone; (2) metformin neither altered basal glycogenesis from [U-14C]glucose and basal lipogenesis from [1-14C]acetate nor insulin binding. These results indicate the ability of this drug to selectively potentiate the acute action of insulin at a postreceptor step in normal liver cells. A prolonged incubation with insulin (16 hours, 5 x 10(-7) mol/L) led the hepatocytes to a state of resistance evidenced by a 50% decrease in their maximal responsiveness and sensitivity to a subsequent acute stimulation by the hormone, as assessed on lipogenesis.

Evidence for the involvement of vicinal sulfhydryl groups in the insulin stimulation of intracellular glucose metabolism in Zajdela hepatoma cells.

Phenylarsine oxide (PhAsO), a dithiol reagent that blocks insulin stimulation of glucose transport in 3T3 L1 cells, also altered insulin stimulation of intracellular glucose metabolism in Zajdela Hepatoma cultured cells. PhAsO (2 microM) similarly inhibited the insulin-induced glycogen and lipid syntheses without modifying the basal level of these processes, cell viability or the ATP content. Prior incubation of the cells with PhAsO did not prevent insulin binding to the cells, or activation of the receptor tyrosine kinase, while it minimally (16%) altered receptor internalization.

Blood pressure in healthy men and women under laboratory and naturalistic conditions.

Thirty healthy nonsmoking men and 30 women underwent a laboratory reactivity assessment with systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) recorded at rest and during behavioral (mirror image tracing, mental arithmetic, color word conflict task and a semistructured Type A interview), and physical tasks (isometric exercise and the cold pressor test). Causal SBP and DBP were measured in a physician's clinic. Four months earlier SBP, DBP and HR had been monitored during a day at work and a day at home.

Blood lipids as related to cardiovascular and neuroendocrine functions under different conditions in healthy males and females.

Correlations were calculated between, on the one hand, total serum cholesterol, low-density (LDL) and high-density (HDL) lipoprotein cholesterol, and triglycerides, and, on the other hand, systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), urinary epinephrine, norepinephrine, and cortisol in 30 healthy males and 30 healthy females, aged 30-50. The cardiovascular and neuroendocrine measurements were obtained under different real-life and laboratory conditions. The most striking finding was that, in men, but not in women, total serum cholesterol was significantly positively correlated with SBP in all conditions (LDL and HDL cholesterol followed the same pattern).

Insulin action is mimicked by polyclonal antireceptor antibodies that activate the insulin receptor tyrosine kinase.

The insulin-like properties of anti-insulin receptor antibodies (P95 Ab) that have been characterized as being directed against the receptor beta-subunit, were studied as probes to assess the interrelationship between insulin action and receptor phosphorylation. When tested on intact cells, P95 Ab mimicked insulin effects. On isolated fat cells, they stimulated 2-deoxyglucose (2-DG) transport and lipogenesis and the P95 antibody maximal effects (173 and 232% of the control values, respectively) represented about 50% of the maximal effects elicited by insulin (317 and 475% of the control values).

Detection and characterization of anionic polypeptide fraction binding sites in rat liver plasma membranes and cultured hepatocytes.

The binding of human 125I-labeled 'anionic polypeptidic fraction' (APF) to purified rat liver plasma membranes was studied. The dissociation constant for this binding was 3.0 micrograms protein/mg membrane protein.

Type A behavior in healthy males and females as related to physiological reactivity and blood lipids.

Type A behavior was assessed in 30 men and 30 women (ages 30-50) by a Videotaped Structured Interview (VSI). Scores for total Type A behavior as well as subcomponents (competitiveness, time urgency, hostility) were examined in relation to cardiovascular and neuroendocrine reactivity during a work day (change from a work-free day) and during laboratory-induced stress (change from resting condition). In addition, Type A and Type B males and females were compared with regard to total serum cholesterol, LDL and HDL cholesterol, and triglycerides.

Body temperature and plasma prolactin and norepinephrine relationships during exercise in a warm environment: effect of dehydration.

The effects of euhydration (Eh) and light (Dh1) and moderate (Dh2) dehydrations on plasma prolactin (PRL) levels were studied in 5 young male volunteers at rest and during exercise to exhaustion (50% of VO2max) in a warm environment (Tdb = 35 degrees C, rh = 20-30%). Light and moderate dehydrations (loss of 1.1 and 1.

Lipoprotein synthesis and secretion by cultured rat hepatocytes. Parallel inhibition of secretion of VLDL, HDL and albumin by monensin.

The biosynthesis and secretion of very-low-density lipoproteins (VLDL) and high-density lipoproteins (HDL) by cultured normal rat hepatocytes was investigated with particular emphasis on its modification by monensin. This acidic ionophore coordinately inhibited the rates of secretion of the several VLDL apolipoproteins and the VLDL lipids, suggesting an effect late in the process of biosynthesis and secretion, probably at the stage of exiting from the Golgi apparatus. The secretion of immunoreactive albumin into the medium was comparably inhibited, implying that the pathway and mechanisms involved in albumin secretion may be closely similar to those for VLDL synthesis and secretion.

Plasma AVP, neurophysin, renin activity, and aldosterone during submaximal exercise performed until exhaustion in trained and untrained men.

The effect of intense muscular work (80% of maximal oxygen uptake) on responses of plasma hormones involved in electrolyte and water balance were measured in 14 male subjects. They were divided into three groups according to their maximal oxygen uptake and the duration of exercise performed until exhaustion: well trained subjects (group I), trained subjects (group II), and untrained subjects (group III). Pulmonary gas exchange, heart rate, rectal and skin temperature, and weight loss were measured as well as hematocrit and plasma and urine sodium and potassium concentrations.

[Determination of lecithin-cholesterol acyltransferase. Studies on the precipitation of beta-lipoproteins by dextran sulphate (author's transl)].

Uncertainties in assays of lecithin-cholesterol acyltransferase (LCAT) are generally related to the degree of isotopic equilibrium obtained by rapid exchange of unesterified cholesterol between the different lipoproteins. A new method is presented based on the precipitation of serum beta-lipoprotein with sulfated polysaccharides prior to the LCAT determination. In the absence of Beta-lipoproteins, more than 7 per cent of serum free cholesterol is esterified in the first hour and the reaction rate is linear for about 2 h.

[Activities of pulmonary phospholipases of fetal rats. Variations during development].

Turnover of adult rat lung phospholipids implies intervention of phospholipases. This work clearly demonstrates: There is in fetal or adult rat lung an inactive form of phospholipase that is convertible to an active form by the action of lysed platelets. An increase of both active and inactive forms of the fetal enzyme with gestational age.

[The effects of Triton WR 1339 on the secretion of bile lipids in the rat].

Rats bearing a biliary fistula received i.v. a solution of Triton WR 1339.