Increase of food intake induced by glucagon in the rat

The effect of intraperitoneal administration of saline, glucose (25 mg/100 g b.w.), insulin (0.025 U/100 g b.w.) and glucagon (50 micrograms/kg b.w.) on glycemia, liver glycogen concentration and food intake was studied on 104 male adult Wistar rats. When saline was injected the amount of food ingested was similar to that expected at the metabolic moment selected for the tests. Glucose administration did not reduce food intake but both insulin and glucagon provoked a threefold increase during the 60 minutes ensuing the injection. The overall ingestion of food during the 24 hours after the injection of the hormones was significantly higher (about 10%) than the control values during the preceding or the succeeding 24 hours. A hyperphagic, rather than a hypophagic effect of glucagon administration is possibly related to the small dose used in the experiments. The mechanisms involved in the increase of food intake due to glucagon are discussed in terms of acceleration of the metabolic reactions that normally prevent large drops of glycemia as glucose utilization proceeds during the inter-meal periods and that in physiological conditions build up until the need for food arises.     

Impaired Leydig Cell Function In Vitro in Testicular Tissue from Human Males with "Sertoli Cell Only" Syndrome

Testicular histopathology in patients with "Sertoli Cell Only" Syndrome is characterized by absence of germinal cells. Some of these patients have high levels of LH in their peripheral blood as well as subnormal serum testosterone levels. This indicates a possible correlation between the lack of germinal cells and an impairment of Leydig cell steroidogenic activity. It has previously been shown that in vitro conversion of tritiated steroid precursors within testicular tissue indicates the Leydig cell steroidogenic activity. In this study we have investigated whether or not testicular tubular cell disorder with lack of germinal cells is related to impairment of the intratesticular steroid metabolism in vitro. Ten patients with testicular histopathology characteristic of "Sertoli cell only" syndrome were investigated and their steroid metabolism patterns were compared with those of 22 control patients. Leydig cell dysfunction was found in the group of patients with SOS; 17 alpha-hydroxylation was significantly lower and the production of 20 alpha-dihydroprogesterone was significantly higher, as compared to the control patients. The Leydig cell impairment may be due to a disturbed influence from the damaged tubules.     

Surgical remodeling of the silhouette by aspiration lipolysis or selective lipectomy

The author, a pioneer in originating the technique of suction lipectomy, discusses in detail the pathophysiology of the fat cell and fat metabolism. In addition, he describes the surgical means by which, since 1977, he has popularized this innovative new approach to the treatment of unsightly fat deposits in many sites in the body, including the thighs, buttocks, abdomen, hips, arms, ankles, breasts, and submental regions.     

Effects of sensory deafferentation on glucose metabolism of muscles during locomotion

We measured the uptake of a radiolabeled analogue of glucose ([3H]FDG) into muscles during treadmill walking so as to determine whether sensory deafferentation of a limb affects the muscles' metabolic response to the exercise. The muscles on the deafferented side took up less tracer than those in the intact side with exercise, but not at rest. Extensor muscles were more affected than flexors by deafferentation. This agrees with the proposal that "reflex" inputs adjust the level of recruitment of motor units by central pattern generators.     

Alterations in alanine metabolism in diabetic dogs during short-term treatment with an artificial B cell

Summary The flux rates of plasma glucose and alanine were studied isotopically (6-³H-glucose and U-¹⁴C-alanine simultaneously) in resting chronically diabetic dogs during short-term treatment with an artificial B cell where the insulin was infused into a peripheral vein. Despite perfect blood glucose control and normal glucose flux rates, the concentration and rates of appearance and disappearance of alanine were significantly elevated in the diabetic animals before, during and after an exogenous glucose load. The incorporation of the carbon moiety of alanine into circulating glucose was also increased, but diminished to a near-normal extent when exogenous glucose was given. The plasma clearance rates for alanine in the diabetic dogs were normal throughout the study. It is concluded that normal blood glucose control in diabetes does not necessarily mean normalization of the entire metabolic network. On the basis of peripheral hyperinsulinaemia alanine formation from glucose and branched chain amino acids is elevated in muscle. This may explain increased flux of alanine despite normal blood glucose control.     

Pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity

The pharmacologic specificity of tolerance to caffeine-induced stimulation of locomotor activity was studied in adult male rats that were given access to either caffeine solution (0.5 or 1.0 mg/ml) or plain water for 10 min every 6 h on a chronic daily basis; daily caffeine intake averaged 41 and 62 mg/kg, respectively. Dose-effect curves were determined for behavioral stimulant and depressant drugs in control and caffeine-treated groups. Drugs were injected IP and locomotor activity was measured for 30 min beginning 35 min later. Rats tolerant to stimulation of locomotor activity by caffeine were also tolerant to theophylline and 7-(2-chloroethyl)theophylline, but not to any of six nonxanthine stimulants, including cocaine, methylphenidate, and d-amphetamine. The adenosine analogs, R(–)-N⁶-2-(phenylisopropyl)adenosine(R(–)-PIA) and 5-(N-ethyl)carboxamidoadenosine (NECA), decreased locomotor activity of control and caffeine-treated (0.5 mg/ml) rats; dose-effect curves in rats consuming caffeine chronically were displaced to the right of the control curves by 10-fold for R(–)-PIA and 100-fold for NECA. Dose-effect curves for the nonadenosine behavioral depressants chlorpromazine and diazepam were unchanged by chronic treatment with caffeine, but the curve for pentobarbital, which is thought to inhibit adenosine receptor binding, was shifted to the right by a factor of 3. Rats withdrawn from chronic caffeine for 24 h were still completely tolerant to caffeine-induced stimulation of locomotor activity. Dose-effect curves for R(–)-PIA and d-amphetamine in rats withdrawn from chronic caffeine for 24 h were not different from curves in control animals. These results indicate that tolerance to caffeine-induced stimulation of locomotor activity is specific to the methylxanthine class of stimulants and is not a property of nonxanthine psychomotor stimulants. Furthermore, the adenosine-antagonist activity of caffeine remains evident even in rats completely tolerant to the stimulant effect of caffeine. These results provide no support for the view that caffeine tolerance is due to enhanced sensitivity of central adenosine systems.A preliminary report of this work appeared in The Pharmacologist (28:140, 1986)     

Are the metabolic characteristics of congenital intraspinal lipoma cells identical to,or different from normal adipocytes?

Congenital intraspinal lipomas are frequently responsible for progressive neurological deficits caused by distortion or compression of the nervous system. Since fat metabolism in these lesions has not been previously studied, the aim of this study was to determine whether intraspinal lipoma cells behave like lipomas or like normal adipocytes. In 11 patients, intraspinal lipoma cells were compared with normal adipocytes isolated from adjacent subcutaneous adipose tissue for the following parameters: lipoprotein lipase (LPL), lipogenesis from U¹⁴C glucose, ß-receptor number, adenylate cyclase activity, cyclic AMP production, and lipolysis in response to ß- and ₂-adrenergic agonists. No significant difference between these two cell populations was found, suggesting that intraspinal lipomas are not lipomatous tumors, but hamartomatous lesions capable of growth and regression along with the changes in the rest of the fatty pool. This emphasizes the danger of an abnormal weight gain, as well as the possible usefulness of an hypocaloric diet in patients who worsen in spite of previous surgery.Research supported by INSERM (CRL 824005 and CRE 854010) and the D.G.R.     

Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET)

To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-¹¹C)-tyrosine by ¹¹C-carboxylation of the appropriate -lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-¹¹C)-Tyrosine in 0.1 N NaH₂PO₄ buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-¹¹C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-¹¹C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma.     

Stretched attend posture,a non-social form of ambivalence,is sensitive to a conflict-reducing drug action

Based upon the ethological element stretched attend to a conspecific, which reflects ambivalence between approach and avoidance in a social context, a simple, non-social behavioral method for studying conflict behavior in mice was investigated. Thus, stretched attend posture (SAP) and other behavioral acts were measured in untreated or drug-treated mice which were individually placed on a perforated platform previously rubbed with foreign male urine and boluses. In naive, untreated mice, the occurrence of SAP was partly housing- and lighting-dependent. After repeated exposure to the test situation, untreated mice showed less SAP, whereas static behavior (immobility and activity at rest) was increased. After single oral treatment with diazepam, clobazam or phenobarbital, SAP was reduced, whereas static behavior or going forwards in SAP was increased. Chlorpromazine and imipramine did not influence SAP. In naive mice, single IP injection of pentylenetetrazol did not significantly increase SAP. The similarity in the behavioral response between experienced, untreated mice and naive animals treated with diazepam, clobazam, or phenobarbital suggests that drug-treated mice behaved as if they were already familiar with the test situation. The latter drug-induced changes are consistent with data obtained in animal models which are based upon the measurement of behavioral inhibition. Under the present test conditions, pentylenetetrazol did not show anxiogenic properties. Nevertheless, the SAP test, based primarily on the measurement of the ambivalence element, offers a simple procedure for examining the conflict-reducing properties of drugs, dispensing with the need of noxious stimuli or prior training.Some of these results were presented at the 15th Annual USGEB/USSBE Meeting in Fribourg, Switzerland (17–18 March 1983) and, published in abstract form in Experientia (1983) 39(6):681–682