Aurora Renauld

Adrenocorticotrophic hormone, cortisol and catecholamine concentrations during insulin hypoglycaemia in dogs anaesthetized with thiopentone

Glucose homeostasis is maintained by complex neuroendocrine control mechanisms. Increases in plasma concentrations of various glucose-raising hormones such as glucagon, catecholamines, adrenocorticotrophic hormone (ACTH), and cortisol are observed under certain conditions associated with stress (haemorrhage and hypoglycaemia). The purpose of this study was to determine the effect of thiopentone anaesthesia on the cathecholamine, ACTH and cortisol response to insulin hypoglycaemia in dogs. Blood sugar (BS), plasma cathecholamine, and ACTH, and serum cortisol concentrations were measured during the course of (1) an intravenous insulin test (ITT) and (2) an ACTH test in conscious and in anaesthetized fasted dogs. During the ITT, the anaesthetized dogs showed a moderate resistance, compared with conscious dogs, to the hypoglycaemic action induced by insulin (blood sugar concentration 30 min after insulin injection: 2.91 ± 0.25 vs 1.93 ± 0.12 mM · L−1; P < 0.01). In addition, decreased epinephrine (220 ± 27 vs 332 ± 32 pg · ml−1 ACTH (65 ± 6 vs 90 ± 5 pg · ml−1) and cortisol (4.48 ± 0.3 vs 6.25 ± 0.5 μg · ml−1) concentrations were detected 60 min after insulin injection (P < 0.01). The norepinephrine response to hypoglycaemia was not altered by anaesthesia (273 ± 33 vs 325 ± 25 pg · ml−1). Anaesthetized dogs showed a decreased cortisol response to ACTH at 45 min (5.68 ± 0.54 vs 8.87 ± 0.47 μg · ml−1) when compared with control dogs (P < 0.001). Haemodynamic variables during anaesthesia showed little changes (P < NS); while respiratory rate was altered (P < 0.01 between 60 and 105 min). Arterial pH was decreased (7.29 ± 0.03 vs 7.36 ± 0.04; P < 0.05) and PaCO2 was increased (6.8 ± 0.3 vs 5.2 ± 0.3; P < 0.01) at 30 min from induction of anaesthesia but little change was seen after the beginning of the ITT and ACTH tests. We conclude that thiopentone anaesthesia provokes a moderate resistance to the hypoglycaemic action of insulin. This does not appear to be related to increases in plasma concentrations of cathecholamines, cortisol or ACTH. Since the hyperglycaemic effects of cathecholamines and glucagon are synergistic it is possible that glucagon plays an important role in the altered blood sugar response to insulin administration.RésuméL’homéostase du glucose sanguin est maintenue par des mécanismes de contrôle neuroendocriniens complexes. On observe une augmentation des concentrations plasmatiques (ou sériques) de plusieurs hormones hyperglycémiantes telles que le glucagon, l’ACTH et le cortisol sous certaines conditions liées au stress chirurgical comme l’hémorragie et l’hypoglycémie. Le but principal de cette étude est de déterminer les effets de l’anesthésie au thiopental sur la réponse, à l’hypoglycémie insulinique, des catécholamines, de l’ACTH et du cortisol. On détermine la glycémie et les concentrations plasmatiques des catécholamines et de l’ACTH, et les niveaux sériques du cortisol pendant 1) le test de tolérance à l’insuline, 2) l’épreuve à l’ACTH chez des chiens éveillés et anesthésiés. Lorsqu’on compare les chiens anesthesias avec les chiens éveillés, on constate que l’injection iv d’insuline provoque sur des mesures aux 30 minutes une insulino-résistance (glycémie: 2,91 ± 0,25 vs 1,93 ± 0,12 mM · L−1; P < 0,01) et une baisse de concentration plasmatique mesurée aux 60 minutes de l’épinéphrine (220 ± 27 vs 332 ±32 pg · ml−1), de l’ACTH (65 ±6 vs 90 ± 5 pg · ml−1) et du cortisol (4,48 ± 0,3 vs 6,25 ± 0,5 μg · ml−1) (P < 0,01). La réponse de la norépinéphrine plasmatique n’est pas modifiée par l’anesthésie (273 ± 33 vs 325 ± 25 pg · ml−1). Quarantecinq minutes après l’injection iv d’ACTH, on constate chez les chiens anesthésiés une diminution de la réponse au cortisol (5,68 ± 0,54 vs 8,87 ± 0,47) comparativement aux contrôles (P < 0,001). Les paramètres hémodynamiques pendant l’anesthésie demeurent inchangés (P < NS). Par contre, la fréquence respiratoire change (P < 0,01 entre 60 et 105 min). Trente minutes après l’induction de l’anesthésie, le pH artériel diminue (7,29 ± 0,03 vs 7,36 ± 0,04: P < 0,05), la PaCO2 augmente (6,8 ± 0,3 vs 5,2 ± 0,3; P < 0,01). On note peu de changements après le début des test de tolérance au glucose et l’épreuve à l’ACTH. A partir de ces données on peut conclure que l’anesthésie au thiopental produit une insulino-résistance modérée. Cet effet ne résulte pas d’une augmentation plasmatique des catécholamines, de l’ACTH ou du cortisol. Au contraire, le niveau sanguin de ces hormones diminue. On énonce comme postulat l’intervention probable du glucagon dans les mécanismes de régulation aigus de la glycémie chez les chiens anesthésiés.

Blood sugar, serum insulin and serum free fatty acid responses to slow graded glucose in thyroxine-treated dogs

SummaryThe effects of short-term (10 days) thyroxine administration (100 µg/kg body weight/die) on the BS, serum IRI and circulating FFA responses to slow, graded glucose stimulation were studied in dogs. The experiments reported demonstrated that the mean basal BS value in thyroxine-treated dogs is higher than that found in untreated controls, and that non-parallel mean BS responses to glucose infusion were observed during the test: the higher curve was found in the thyroxine-treated group. Mean basal serum IRI was similar in both groups, and parallel insulinemic responses to hyperglycemia were observed. Mean serum IRI responses as a function of time from the start of infusion in hyperthyroid dogs were lower than those observed in untreated controls. Mean basal serum FFA levels in both groups did not differ, and parallel serum FFA curves were found during the test. Thyroxine treatment caused a better lipogenic response to combined hyperglycemia/hyperinsulinemia and a steep subsequent rebound of serum FFA, as compared to untreated controls. We conclude that dogs with recently induced hyperthyroidism show an impairment in the net glucose uptake by tissues, a poor insulinemic response to glucose, a good lipogenic response and a sharp subsequent rebound of serum FFA. The high BS curve, the high tissue FFA response to insulin antagonists and the high mean BS level in the fasting condition might be accounted for by a thyroxine-induced active production of cAMP in body cells, but the low insulin secretion evidently is due to other mechanisms.

Blood sugar, serum insulin and serum non- esterified fatty acid levels during thiopentone anaesthesia in dogs

The purpose of this study was to determine the effect of thiopentone anaesthesia on glucose metabolism. Blood sugar (BS), serum immunoreactive insulin (IRI) and serum non-esterified fatty acid (NEFA) concentrations were measured during the course of (1) an intravenous glucose tolerance test (IVGTT), and (2) an intravenous insulin test (ITT), in conscious and anaesthetized fasted dogs. The IVGTTs were repeated in dogs under alpha-or beta-adrenergic blockade, induced by phentolamine or propranolol. During the IVGTT, the anaesthetized dogs showed glucose intolerance (blood sugar levels were higher than in the control group) and little serum IRI response to hyperglycaemia was detected. An attenuated initial decrease and a slower rebound of NEFA concentration was observed in anaesthetized animals than in controls. Phentolamine administration (5 mg · kg−1 iv) partly restored the IRI response without affecting the BS levels; propanolol (1 mg · kg−1 iv) had no effect. Anaesthetized dogs showed a moderate resistance to insulin induced hypoglycaemic action and a lack of serum NEFA response during counter-regulation of hypoglycaemia, while in conscious controls an intense rebound was observed. Hyperinsulinaemia after iv insulin administration was longer in anaesthetized dogs than in controls. The insulin distribution space was 78% of body weight and insulin t1/2 in blood group compared with 54% and 16 min, in controls. We conclude that thiopentone provokes disturbances in glucose and serum NEFA metabolisms and abolishes the serum IRI response to hyperglycaemia. These effects are influenced by extrapancreatic factors regulating serum IRI levels and by an alpha-adrenergic mechanism, via the inhibition of insulin secretion.RésuméCette étude porte sur les effets de l’anesthésie au thiopental sur la glycémie, l’insulinémie et la concentration des acides gras non-estérifiés (AGNE) sur des chiens en réponse à un test d’hyperglycémie provoquée et à une injection intraveineuse d’insuline. Le groupe contrôle se compose de chiens éveillés. Chez les chiens anesthésiés, on constate après le test d’hyperglycémie provoquée, une intolérance au glucose, une absence de réponse insulinique 5 min après l’injection du glucose (29 ± 15 μU · ml−1 comparativement à 85 ± 8 μU · ml−1 pour les contrôles) et une baisse moins importante des AGNE. Un bloc β- adrénergique au propanolol n’a pas modifié ces résultats. Cependant, l’administration de phentolamine (blocage α- adrénergique) rétablit partiellement la réponse insulinique sans modifier la glycémie. Chez le chien anesthesié, l’injection intraveineuse d’insuline entraîne une résistance aux actions hypoglycémiantes de l’insuline et lipolytique des hormones antiinsuliniques. L’insuline injectée lors du test d’hyperglycémie provoquée avait une demi-vie plus longue (27,5 min contre 16 min) et un volume de distribution plus grand (78% contre 54%) chez les chiens anesthésiés que chez les contrôles. On peut conclure que la réponse insulinique à l’hyperglycémie diminue chez les chiens anesthésiés au thiopental. En toute probabilité, on peut attribuer ces résultats à une association de facteurs extrapancréatiques auxquels s’ajoute un facteur α-adrénergique inhibitoire de la sécrétion insulinique.

The effect of chronic prolactin administration upon the blood sugar, insulin and free fatty acid response to a glucose load in the dog

RiassuntoGli AA. hanno studiato l’effetto della somministrazione cronica di prolattina sulla glicemia e sui livelli sierici dell’IRI e dei NEFA, in cani normali, prima e durante IVGTT. Essi hanno osservato che la somministrazione cronica di prolattina: 1) non modifica i livelli glicemici e di IRI, mentre produce soltanto un lieve e non significativo aumento nella concentrazione sierica dei NEFA; 2) induce una moderata diminuzione della risposta glicemica nei primi 15 min dopo il carico di glucosio, mentre la glicemia media, il valore k ed i livelli sierici di IRI non risultano modificati; 3) accelera lievemente sia la caduta della NEFAemia che si osserva per effetto del carico, sia la sua risalita verso i valori basali dopo il raggiungimento di un minimo, e ciò nonostante la presenza di elevati livelli glicemici ed insulinemici. In cani sottoposti a trattamento cronico con prolattina, la NEFAemia è più elevata di quella che si osserva in animali di controllo non trattati nella fase finale del test, allorché i livelli glicemici ed insulinemici sono già tornati ai valori di partenza. Viene discusso il significato fisiologico di tali variazioni.RésuméOn a étudié l’effet d’une thérapie chronique avec prolactine sur la glycémie et les niveaux d’insuline sérique immunoréactive et des acides gras libres des chiens normaux à jeun, avant et pendant une épreuve de tolérance au glucose i.v. On a observé que: 1) la thérapie semble ne pas affecter chez ces animaux à jeun les niveaux de glucose sanguin et d’insuline sérique immunoréactive et produit seulement une légère mais insignifiante élévation de la concentration des acides gras libres sériques; 2) quoique la thérapie induit une légère déscente des niveaux de la glycémie pendant les premières 15 min après la surcharge de glucose, ni la glycémie moyenne pendant l’épreuve ni le k du glucose n’ont pas été affectés; la courbe d’insuline sérique immunoréactive pendant l’épreuve s’est maintenue également inalterée; 3) la thérapie accélère légèrement la chute de la concentration des acides gras libres sériques suivant la surcharge de glucose; le retour à la ligne de base après une descente au minimum est aussi accéléré par la thérapie en dépit des hauts niveaux d’insuline sérique et de glucose sanguin; à la fin de l’expérience la concentration des acides gras libres sériques est definitivement surnormale, pendant que la glycémie et l’insulinémie sont déjà revenues à la ligne de base, chez les chiens traités. La signification physiologique de ces changements est discutée.ResumenSe estudió el efecto del tratamiento crónico con prolactina sobre los niveles de glucemia, insulina sérica inmuno-reactiva y ácidos grasos libres en perros normales en la condición postabsorptiva, antes y durante una prueba i.v. de tolerancia a la glucosa. Se observó: 1) en la condición post-absorptiva la terapia no afectó ni los niveles de glucemia ni los de insulina sérica inmuno-reactiva, pero sí indujo un muy pequeño aumento, no significativo, en la concentración de ácidos grasos libres circulantes en estos animales; 2) el tratamiento provocó una moderada disminución en los niveles de glucemia alcanzados durante los primeros 15 min luego de la sobrecarga de glucosa, pero no afectó la glucemia promedio durante la prueba, ni el valor k, ni tampoco el perfil de insulina sérica inmuno-reactiva; 3) el tratamiento aceleró levemente la caída de los niveles de ácidos grasos libres por la sobrecarga glucosada, como así también su retorno a la línea de base luego de pasar por un mínimo, a pesar de los elevados niveles de glucemia e insulinemia existentes. La concentración de ácidos grasos libres en suero de los perros tratados con prolactina crónicamente fué mayor que en los controles no inyectados al fin de la prueba, momento en que la glucemia e insulinemia habían retornado a sus valores basales. Se discute el significado fisiológico de todos estos cambios ocasionados por la hormona.ZusammenfassungDie Wirkung einer chronischen Prolactinbehandlung auf den Blutzucker, das immunologisch messbare Seruminsulin und die freien Fettsäuren wurde an normalen Hunden im post-absorptiven Zustand und vor und nach intravenöser Glukosebelastung verfolgt. Folgendes wurde beobachtet: 1) im post-absorptiven Zustand hatte die Behandlung keinen Einfluss auf Blutzucker und Serum IRI, bewirkte aber einen sehr bescheidenen, nicht signifikanten Anstieg der zirkulierenden FFA; 2) die Behandlung bewirkte eine mässige Verringerung der in den ersten 15 Min. nach der Glukosebelastung erreichten Blutzuckerwerte, ohne jedoch den mittleren Blutzuckerspiegel oder das IRI-Profil der Probe zu beeinflussen; 3) die Behandlung beschleunigte in geringem Ausmass den FFA-Abfall nach der Glukosebelastung wie auch nach Erreichung eines Minimuns die Rückkehr zum Ausgangswert trotz der hohen Blutzucker- und Seruminsulin-Werte. Am Ende der Probe, d.h. im Moment, wo Blutzucker und Insulinämie zu den Ausgangswerten zurückgekehrt sind, war die FFA-Konzentration im Serum der mit Prolactin behandelten Hunde höher als die der unbehandelten Tiere. Die physiologische Bedeutung dieser von dem Hormon verursachten Veränderungen wird besprochen.SummaryThe effect of chronic prolactin treatment on blood sugar, serum immunoreactive insulin and free fatty acid levels has been studied in normal dogs in the post-absorptive condition and during an i.v. glucose tolerance test. It was observed that: 1) the chronic administration of prolactin failed to affect either blood sugar or serum immunoreactive insulin levels in these animals in the post-absorptive condition and induced a very minor non-significant increase in serum free fatty acid concentration; 2) although prolactin chronic administration induced a moderate reduction in the blood sugar response in the first fifteen min after the glucose load, the average glucose level, kglucose, and serum IRI profile were unaffected; 3) prolactin administration slightly accelerated the fall of FFA levels during glucose administration as well as the return to baseline values in spite of the high blood glucose and insulin levels. In dogs having undergone chronic prolactin treatment the serum FFA concentration was higher than in non injected animals in the final stages of the test, i.e. at the moment when blood glucose and insulin had returned to basal levels. The physiological significance of these changes is discussed.

Relationship between Hyperinsulinemia and Ambulatory Blood Pressure Monitoring of Lean and Overweight Male Hypertensives

Objective To elucidate the role of hypertension as part of a state of insulin resistance. Methods Thirty-one uncomplicated hypertensive men not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period and 10 lean normotensive controls were compared. Hypertensive men were divided according to their body mass index into three groups. All subjects came to the clinic for measurements of height, weight, hip and waist circumferences, and sitting blood pressure, and to begin 24 h ambulatory blood pressure monitoring. Plasma glucose and insulin levels were measured during a 2 h oral glucose (75 g)-tolerance test. For the hypertensive population as a whole, behaviors of studied variables among dippers (n= 18) and nondippers (n= 13) were determined. Results During oral glucose-tolerance testing blood glucose levels after 60 min and 120 min were significantly higher (P < 0.05) in members of the high body mass index group than they were in members of the low body mass index group. insulin levels of members of the high and middle body mass index groups were higher than those of members of the low body mass index group after 60 min (P < 0.05 for both comparisons) and 120 min (P < 0.05 for both comparisons). The mean serum insulin level in members of the low body mass index group was significantly higher than that in normotensives after 30 min, 60 min and 120 min (P < 0.05 for all three comparisons). The mean serum insulin: Plasma glucose ratio for men in the low BMI group was significantly higher than that for normotensives after 60 min and 120 min (P < 0.05 for both comparisons). Correlations of blood pressure and insulin levels were not significant. Levels of high-density lipoprotein cholesterol and triglycerides were lower in members of the group with high body mass index than they were in members of the group with low body mass index. Total cholesterol: High-density lipoprotein cholesterol ratio was higher for members of the high body mass index group than it was for members of the middle body mass index group. Weight, body mass index, casual systolic blood pressure, 24 h average systolic blood pressure and diastolic blood pressure, 0700-2300 h systolic blood pressure, and 24 h average heart rate-systolic blood pressure product of dippers were significantly lower than those of nondippers. Conclusions These results suggest that hypertension and being overweight have additive effects increasing insulinemia and that being overweight is associated with a significantly lower nocturnal fall in blood pressure. J Cardiovasc Risk 5: 25-30

Effect of estrogens on blood sugar, serum insulin and serum free fatty acids, and pancreas cytology in female dogs

SummaryWe analyzed the changes in blood sugar (BS), serum immunoreactive insulin (IRI), circulating free fatty acids (FFA) and pancreatic cytology caused by estrogenization at low pharmacological dosage in female dogs. Vehicle-injected and untreated controls (anestrus) were studied as well. Neither mean basal BS nor basal serum IRI was modified by the treatments, while the mean basal serum FFA value was raised. Glucose tolerance was not modified by the estrogens while glucosey-mean was significantly raised. Hyperglycemia was higher for a longer time in estrogenized animals compared to both controls, while the profiles of hyperinsulinemia coincided. In the estrogen-treated bitches, the pancreatic B-cells contained scarse brown-stained granules near their vascular pole, as shown by an immunochemical method. In the peripheral part of the pancreas, near the acini, some solitary, poorly β-granulated B-cells were present. During the IVGTT, serum FFA reached lower values for a longer time in the estrogenized bitches as compared to those found in both control groups. Insulin-induced hypoglycemia in the estrogenized animals coincided with the one evoked in the vehicle controls; in the semilog relationship of serum IRI and time,y-mean was lower than that observed in oil-injected controls, and insulin space was larger. The serum FFA levels of the estrogenized bitches, very high in the basal conditions, did not respond to insulin administration, and were above those found in untreated controls and also in vehicle-injected controls just at the beginning of the test. These results are discussed. We came to the conclusion that estrogenization causes some glucose intolerance in bitches while insulin sensitivity remains normal in the IVITT as studied measuring BS. The glucose intolerance is thought to be related to a reduction in glucose space and occurs despite the normality of the serum IRI response. The pancreas must have an intense secretory responsein vivo so as to maintain normal IRI activity despite degranulation of the islets of Langerhans and poor islet hypertrophy and neoformation. The serum FFA changes are thought to contribute towards the tendency to adiposity in these animals.

Influence of estrogen-progesterone sequential administration on pancreas cytology. Serum insulin and metabolic adjustments in female dogs

SummaryIn bitches in anestrus, artificial endometrial sex cycles were induced. Estrus was induced by 17β-estradiol benzoate administration; matched untreated and vehicle-treated controls were studied. Early metadiestrus (6th day after appearance of metestrum cells in vaginal smears) was induced by the sequential administration of 17β-estradiol benzoate and progesterone: matched studies with only one hormone or vehicles were also carried out. In different groups of animals, blood sugar (BS), serum immunoreactive insulin (IRI) and serum free fatty acids (FFA) in the basal conditions and during glucose and insulin tests were studied. Insulin was immunocytolocalized in sections of pancreas from a part of these animals. Size and insulin content in Langerhans islets were measured by morphometric and cytospectrophotometric computerized analysis. Extrapancreatic factors — space of distribution, t½ in blood stream — regulating serum IRI and BS levels were calculated. The hypoglycemic effect of insulin was enhanced by estrogenization, together with insulin accumulation in Langerhans islets. Progesterone treatment caused mild insulin resistance together with depletion of pancreatic insulin stores in the long run. Glucose tolerance of progesterone-injected bitches was improved after estrogen priming with greater space of distribution of glucose. Furthermore, a high basal serum FFA levels in bitches receiving the hormone sequence was observed. We may therefore conclude that the metabolic and endocrine changes induced in bitches by artificial sex cycles converge towards excellent BS homeostasis leads to the replenishing of pancreatic insulin stores, so that estrogen-progesterone administration in sequence appears to be, in this experimental condition, non-diabetogenic.

Blood sugar, serum insulin and serum free fatty acid responses to graded glucose pulses in hypothyroid dogs

SummaryThe actions of hypothyroidism on BS, serum IRI and circulating FFA profiles observed in response to single glucose pulses at three levels of stimulation (1.00, 0.66 and 0.33 g/kg body weight) in male dogs were studied. Hypothyroidism modified neither of the mean basal values of these variables. There were different mean BS responses for every time and dose with significant interaction between the two. The BS curves at different doses were not parallel. There was a different time effect for every dose of glucose, and normal and hypothyroid dogs did not differ in this respect. The mean serum IRI responses found in normal and hypothyroid dogs were different; the mean responses at different times also differed, and there were significant normality-time and dose-time interactions. If the hypothyroid dogs and the euthyroid controls received a particular dose of glucose, a significant time effect on the serum IRI level was observed. In the normal dogs receiving glucose dose 1.00, a significant serum IRI response between 5 and 25 min was observed; in the hypothyroid dogs receiving a similar treatment, the significant response lasted from 5 to 45 min. In the normal dogs receiving glucose dose 0.66, the response was significant only at 5 min, and the serum IRI levels were below baseline between 60 and 90 min, while in the hypothyroid dogs the IRI response lasted from 5 to 25 min. In both normal and hypothyroid dogs receiving the 0.33 dose, the responses were significant between 5 and 25 min. As for the mean serum FFA responses to glucose, they were different at every time, and a significant normality-time interaction was found. In the euthyroid controls, the response lasted from 5 to 60 min, while it was longer in the hypothyroid dogs, lasting from 5 min after glucose injection until the end of the test.

Quantitation of insulin stores in Langerhans islets by combined immunohistochemistry and computerized microspectrophotometric analysis

Histology, size, and insulin content of Langerhans islets from normal and recent experimental hyperthyroid (REH) dogs were studied. Insulin localization in the islets was revealed by immunohistochemistry, and the remaining two variables were analyzed by computerized microspectrophotometry according to an original technique described here. Observed under the light microscope, the REH dog pancreas section shows larger than normal islets whose scarce beta-granules are mainly located near B-cell borders and grouped along capillaries. The brown areas occupied by insulin in Langerhans islets from REH and normal dogs (mean±SEM) are 5182±311 and 4236±287 μm2, the total mean insulin amount per respective islet section — as expressed in absorbance arbitrary units — is 1108 and 1846, and the light absorbances per such area units are 0.214±0.070 and 0.436±0.060, respectively. Measuring these variables in dog and human (large) pancreases by the conventional methods successfully used for small pancreases would have been technically impossible.

Effects of short-term thyroxine treatment on pancreatic cytology and responses of blood sugar, serum insulin and serum free fatty acids to epinephrine infusion

The influence of short-term treatment with l-thyroxine on pancreatic histology and on the responses of glycemia, insulinemia and serum free fatty acids to a continuous l-epinephrine infusion in the absence or presence of alpha- and beta-adrenergic blockade was studied in male dogs. l-Epinephrine dosage: 0.06 microgram/kg body weight/min for 55 min. Two experimental groups were studied, one treated for 10 days with sodium l-thyroxine, one daily dose of 100 micrograms/kg body weight, the other of untreated controls. Three alternative treatments were applied to dogs of both groups: 1) no treatment; 2) alpha-adrenergic blockade with phentolamine (2.0 mg/kg body weight, 35 min before starting the l-epinephrine infusion); 3) beta-adrenergic blockade with propranolol (0.3 mg/kg body weight, 20 min before starting the l-epinephrine infusion). Body weight, rectal temperature, heart and respiratory rates were used as guidelines to assess experimental hyperthyroidism. Insulin immunocytolocalization was also studied in the Langerhans islets of T4-treated and control dogs. Body weight decreased and rectal temperature did not vary as a result of thyroxine administration which had no significant effect on respiratory and heart rate. The mean number of breaths from 0 to 120 min from the start of l-epinephrine infusion decreased in both T4-treated and control dogs submitted to propranolol blockage compared to non-blocked animals; phentolamine had no effect on the respiratory rate. Thyroxine treatment did not modify the number of heart beats, but phentolamine blockade had a different effect in T4-treated compared to control dogs whereas propranolol had similar effects in these two groups. Histological examination of the Langerhans islets of dogs submitted to short-term thyroxine treatment showed degranulation though no vacuolation. Most of the beta-granules contained in the B-cells of these islets were found near the cell membrane, thus forming a dark brown line after the immunochemical reaction. Since negative images of B-cell nuclei and vascular spaces were predominant in these specimens, the pancreas of T4-treated dogs presented a mesh structure. In dogs submitted to short-term thyroxine treatment, the hyperglycemic response to l-epinephrine was enhanced and prolonged as compared to untreated controls. In normal dogs, this response is mainly mediated by alpha-adrenergic receptors while beta-receptors hardly influence this response.(ABSTRACT TRUNCATED AT 400 WORDS)