Insulin resistance and hypertension in postmenopausal women.

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.

Altered circadian blood pressure profile in patients with active acromegaly. Relationship with left ventricular mass and hormonal values.

To determine the relationships between the circadian blood pressure profile and left ventricular mass, hormonal pattern and insulin sensitivity indices in patients with active acromegaly, ambulatory 24-h blood pressure monitoring (ABPM) was recorded in 25 subjects (47.0 +/- 15.1 years, range 23-72). Serum growth hormone (GH) and insulin-like growth factor-1, fasting and mean plasma glucose and insulin during oral glucose tolerance test (OGTT), insulinogenic index, the sum of the plasma insulin levels and the homeostasis model insulin resistance index (Homa's index) were determined. Left ventricular mass index (LVMI) was calculated from two-dimensional guided M-mode echocardiogram. The prevalence of hypertension was 56% (n = 14) and 40% (n = 10) according to sphygmomanometric measurements and ABPM, respectively. Non-dipping profile was observed in six of 10 hypertensives and in six of 15 normotensives. Serum growth hormone, fasting glucose, the area under the serum insulin curve and LVMI were higher for acromegalics with non-dipping profile than for dippers (all of them, P < 0.05). In non-dippers daytime heart rate was higher than night time (P < 0.001). In conclusion, the main observations in the present study suggested that both normotensive and hypertensive acromegalics had a highly prevalent non-dipping profile with a preserved circadian pattern of heart rate, that was associated with higher levels of serum GH. The disturbance in nocturnal blood fall in normotensives was associated with a decreased insulin sensitivity. The role of GH in blood pressure circadian rhythm regulation in essential hypertension deserves further studies.

Offspring of streptozotocin diabetic rats: size changes in Langerhans islets with time after birth.

It has been demonstrated that, in the diabetic rat, pregnancy and lactation are severely altered: in this study, we have measured the size of Langerhans islets of rat pups, the offspring of experimental diabetic mothers and nondiabetic controls. Diabetes was induced through streptozotocin administration (dose, 60 mg/kg body wt.). This drug was injected in every animal; their blood sugar was measured 1 week later (Haemo-Glukotest, Boehringer Mannheim), and they were then separated into three groups according to their fasting blood sugar levels: (a) severe diabetics (above 16.5 mM/l); (b) mild diabetics (6.5-16.5 mM/l); and (c) nondiabetic normals. They received insulin therapy (2-4 I.U./day) as the mild diabetics exhibited a slightly higher than normal fasting blood sugar, and the diabetic ones, above 15 mM/l. The areas of Langerhans islets of pups were measured 1 and 5 days after parturition; pancreas sections were dyed (haematoxylin-eosin) and morphometry was then performed using a digitalized magnetic tabloid connected to a Zeiss Morphomat 30 (Kontron). On the first day after parturition, the pancreas section areas in pups from mildly and severely diabetic mothers were smaller than those in neonates from nondiabetic controls (P < 0.001). The areas in neonates from severely diabetic mothers showed a more intense decrease than those from mildly diabetic animals (P < 0.01). On day 5 after delivery, the areas of Langerhans islets in offspring from normal mothers decreased and those in pups from diabetic mothers tended to normalize (P < 0.01), particularly those from the severely sick group (P < 0.01). We conclude that after parturition the offspring is no longer exposed to the high blood sugar levels found in both diabetic groups of mothers, thereby no hyperinsulinemia is needed; as time elapses, then, the area of their Langerhans islets tends to normalization.

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 microns2, 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.

Identification of in vitro cytochrome P450 modulators to detect induction by prototype inducers in the mallard duckling (Anas platyrhynchos).

Seven modulators of mammalian monooxygenase activity were screened for their ability to selectively stimulate or inhibit in vitro monooxygenase activities of hepatic microsomes from mallard ducklings treated with phenobarbital, beta-naphthoflavone, 3,3',4,4',5-pentachlorobiphenyl or vehicle. Microsomes were assayed fluorometrically for four monooxygenases: benzyloxy-, ethoxy-, methoxy-, and pentoxyresorufin-O-dealkylase, in combination with each of the seven modulators. Four combinations: alpha-naphthoflavone and 2-methylbenzimidazole with benzyloxyresorufin, and Proadifen with methoxy- and ethoxyresorufin, respectively, were evaluated further. beta-Naphthoflavone-treated groups were clearly distinguished from the corn oil vehicle control group by all of the assays and by the effects of the modulators in three of the four assay/modulator combinations. Enzyme activities of the phenobarbital and saline groups were statistically similar (P > or = 0.05) when assayed without modulator added, but each assay/modulator combination distinguished between these groups. The PCB-treated group was distinguished from the corn oil vehicle control group only for BROD activity, with or without the presence of modulator. Graphing of per cent modulation of BROD activity versus initial BROD activity provided the clearest distinction between all of the study groups. Identification of these selective in vitro modulators may improve detection and measurement of low level cytochrome P450 induction in avian species. Also, both the monooxygenase activities induced and the impacts of the modulators indicated differences between mammalian and avian cytochromes P450.

Effect of glucose infusion in dogs on blood sugar, insulinemia and serum free fatty acid responses.

A glucose dose-response study, in normal dogs, was performed in vivo. Glucose doses: a) priming 700 mg/kg body wt, i.v.; b) intravenous infusions: 20 (Group I), 28 (Group II), 44 (Group III) and 100 mg/kg body wt/min (Group IV) for 60 min. The following responses were studied: blood sugar, serum immunoreactive insulin and serum free fatty acids. There were significant effects of the dose of infused glucose on blood sugar and serum insulin integrated responses; the integrated serum free fatty acid response was not influenced. Mean integrated blood sugar responses in groups I, II and III coincided, while that observed in Group IV was increased. Mean integrated serum insulin response in group III was above those found in I, II and IV; the response in II was below the one detected in IV. In groups I and II, there was a linear inverse relationship of blood sugar to serum insulin integrated responses; this relationship vanished as data from groups III and IV were also included in the calculation of respective product-moment correlation coefficient. There was a significant effect of the dose of infused glucose on the insulinogenic index during glucose test. Mean insulinogenic indices in groups II and IV were below that of group III. A small unique peak of insulin response in group I during glucose infusion test was observed. A typical biphasic insulin response in systemic venous blood of animals of group II, was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Natural estrous cycle in normal and diabetic bitches in relation to glucose and insulin tests.

The influence of spontaneous "sex seasons" on blood sugar (BS) and serum insulin levels was studied in bitches with natural diabetes mellitus (DM) and normal controls, in the basal condition and during glucose and insulin tests, was studied. DM increased basal BS, reduced glucose tolerance, distribution space (DS) and clearance from blood, and induced resistance to insulin hypoglycemic action. In normals occurrence of "seasons", inconsistently modified basal BS, increased glucose tolerance and DS; during estrogenic phase (EP), these variables were above those during luteal phase (LP). In diabetics at LP, BS found in lasting condition and during glucose test were higher than in diabetic bitches at EP (respective values at anestrous (A) in between) and glucose DS was smaller. Rate of glucose clearance from blood remained unaffected by "seasons" in both dog groups. Basal serum IRI was not modified by DM or "seasons". In normals, serum IRI response to glucose load was nonsignificant during A and increased during the "seasons"; either insulin DS or the rate of insulin clearance from blood stream remained unchanged under the circumstances, the increase being mediated by insulin secretion. During EP, the increase was particularly intense and mean insulinogenic index (MII) rose. During LP, MII returned to A value, whereby diabetic states might be manifest. Serum IRI profiles during insulin test were not modified by "seasons" in normal bitches; such response in diabetic bitches was intense during A, then decreased (EP) or was later abolished (LP). Either in normal or diabetic bitches, the sensitivity to exogenous insulin hypoglycemic action remained unchanged in spite of "seasons". In diabetic bitches at A, serum IRI after glucose challenge peaked higher than in respective normal controls (insulin clearance and insulin DS were similar): they exhibited relative insulin shortage and resistance to insulin hypoglycemic action partly compensated by promoted insulin secretion. Along with "season", abolished serum IRI response to glucose load in diabetics was observed. During EP, extrapancreatic factors regulating serum IRI concentration and MII did not change in respect to A, whereby abolishment appears mediated by depressed insulin secretion. During LP, insulin antagonism in conjunction with 1) absolute insulin deficiency and 2) intense decrease in MII appears as a powerful factor exposing diabetic bitches to a severe or fatal derangement in diabetic disease.

[Effects of beta-adrenergic blocking with propranolol on the mechanisms of glucose regulation in the dog]. / Efectos del bloqueo beta-adrenérgico con propranolol sobre los mecanismos de regulación de la glucemia en el perro.

Propranolol (P) administration is known to cause hypoglycemia in insulin-dependent diabetic patients. The mechanisms whereby this response is produced remain controversial. Some authors postulate an inhibition in the beta-adrenergic action of catecholamines, responsible for hepatic glycogenolysis, while others indicate that these hormones are not so important in the regulation of blood sugar (BS) level. The present studies were undertaken to assess the mechanism whereby hypoglycemia is developed in the dog, with or without beta-adrenergic blockade. Unanesthetized male mongrel dogs were used, weighing 10-20 kg body wt., fed on dog chow pellets and water ad libitum up to 18-22 hours before the test performances. The dogs were randomly grouped into two groups, A and B in which the effect of P on several hormonal and metabolic responses basally and during insulin (I) test, were respectively studied. Group A was constituted by two subgroups of 6 animals each; the animals of one subgroup were beta-blocked, receiving P p.o. for 10 days (80 mg every 8 hours); the dogs of the remaining subgroup received only P excipient in the same way as the treated ones, for the same period. As P treatment was completed, blood samples were taken by venipuncture, in a peripheral vein, at 0 and 60 min. Some biological controls of beta-blockade, assessed at 0, 30 and 60 min, indicated that mean pulse rate (+/- SE) in the control dogs was 123 +/- 2, 128 +/- 2 and 128 +/- 3 beats/min while in the P treated ones was 106 +/- 2, 103 +/- 1 and 103 +/- 3 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic AMP infusion and blood sugar, serum insulin and serum nonesterified fatty acid responses to glucose in recent experimental hyperthyroid dogs.

Recent experimental hyperthyroid (REH) dogs exhibit poor "in vivo" insulin responses to glucose probably due to a failure somewhere in cAMP-adenylate cyclase system. The actions of exogenous cAMP on these responses and on the regulation of blood sugar (BS) and serum nonesterified fatty acids (NEFA) during glucose infusion tests (GIT) in REH and normal dogs were studied here. Hyperthyroidism was induced by 1-thyroxine administration (100 micrograms/kg body wt./die, 10 days). GIT consisted of i.v. glucose-priming followed by glucose i.v. continuous infusion (60 min). cAMP (0, 33 or 66 mg/kg body wt./min) was infused alone (30 min) and then overlapped to gluco-se infusion (60 min). Peripheral veins were used for infusions and blood sample withdrawal. BS, serum inmunoreactive insulin (IRI) and serum NEFA concentrations, basally and throughout the test, were measured. Basally, there was neither action nor interaction of hyperthyroidism and exogenous cAMP on these variables. During the GIT, the BS levels remained unaffected by hyperthyroidism; cAMP increased them, but failed to interact with hyperthyroidism. cAMP noninfused normal dogs responded to hyperglycemia with hyperinsulinemia, whereas REH dogs noninfused the nucleotide did not. cAMP administration at a high dose promoted their response in normal and REH dogs, particularly in the former; in the latter, the response was still lower than in cAMP noninfused normal controls. Although recent hyperthyroidism increased serum NEFA basal level, it exerted neither action nor interaction with the infused cAMP on serum NEFA during GIT. Results are discussed on the basis that the abolished insulin secretion "in vivo" characterizing the REH dogs, related to beta-adrenergic deficiency, can be for the most part restored by exogenous cAMP administration, despite which some glucose and triglyceride metabolism impairments are developed.

Tumor necrosis factor expressed by primary hippocampal neurons and SH-SY5Y cells is regulated by alpha(2)-adrenergic receptor activation.

Neuron expression of the cytokine tumor necrosis factor-alpha (TNF), and the regulation of the levels of TNF by alpha(2)-adrenergic receptor activation were investigated. Adult rat hippocampal neurons and phorbol ester (PMA)-differentiated SH-SY5Y cells were examined. Intracellular levels of TNF mRNA accumulation, as well as TNF protein and that released into the supernatant were quantified by in situ hybridization, immunocytochemistry and bioanalysis, respectively. Both neuron cultures demonstrated constitutive production of TNF. Activation of the alpha(2)-adrenergic receptor increased intracellular levels of TNF mRNA and protein in SH-SY5Y cells after addition of graded concentrations of the selective agonist, Brimonidine (UK-14304) to parallel cultures. Intracellular levels of mRNA were increased in a concentration-dependent fashion within 15 min of UK-14304 addition and were sustained during 24 hr of receptor activation. In addition, the levels of TNF in the supernatant were increased in both types of neuron cultures within 15 min of alpha(2)-adrenergic receptor activation. Furthermore, levels of TNF significantly increased in the supernatants of both neuron cultures after potassium-induced depolarization. A reduction in this depolarization-induced release occurred in hippocampal neuron cultures after exposure to the sympathomimetic tyramine with media replacement to deplete endogenous catecholamines. This finding reveals a role for endogenous catecholamines in the regulation of TNF production. Potassium-induced depolarization resulted in the release of TNF in hippocampal neuron cultures within 15 min but not until 24 hr in SH-SY5Y cultures demonstrating a temporally mediated event dependent upon cell type. Neuron expression of TNF, regulated by alpha(2)-adrenergic receptor activation demonstrates not only how a neuron controls its own production of this pleiotropic cytokine, but also displays a normal role for neurons in directing the many functions of TNF.

Influence of exogenous ATP on blood sugar, serum insulin and serum free fatty acids in short-term experimental hyperthyroid dogs and in euthyroid controls.

We studied the influence of ATP administration on blood sugar (BS), serum immunoreactive insulin (IRI) and serum free fatty acid (FFA) responses to glucose-induced hyperglycemia in short-term experimental hyperthyroid (STEH) dogs and in euthyroid controls. Hyperthyroidism was induced by a 10-day s.c. treatment with 100 micrograms/kg body weight 1-thyroxine. Glucose challenge was performed by i.v. infusion (700 mg/kg body weight as a priming dose, followed by 20 mg/kg body weight/min for 60 min). ATP (1 mg/kg body weight/min) was infused for 100 min 40 min before and 60 min during glucose administration). Glucose-induced hyperglycemia was more prolonged in the hyperthyroid group. ATP treatment did not affect the BS profile of controls but raised that of STEH animals. In the normal controls the insulinemic response to hyperglycemia was enhanced during ATP infusion. By contrast, in the STEH dogs insulin levels during glucose infusion was lower than in controls and did not significantly increase when ATP was added. ATP infusion induced a significant elevation of serum FFA, which was more pronounced in hyperthyroid animals with a greater fall during glucose administration and a marked increase during the period of recovery from hyperglycemia. In conclusion, we postulate that short-term hyperthyroidism in dogs may inhibit adenylate cyclase function in pancreatic B-cells and chiefly stimulate the action of cAMP-phosphodiesterase activity, thereby affecting insulin secretion.

Blood sugar serum insulin and free fatty acid levels in normal dogs. Sex differences.

Sex influences on blood sugar, serum immunoreactive insulin and free fatty acid levels in normal dogs, basally and during intravenous glucose tolerance tests, were studied. Serum free fatty acid levels were the variable most affected by sex in our study. They were high in males in the post-absorptive condition, with a prompt, sharp suppressibility by combined hyperglycaemia and hyperinsulinaemia, followed by intense, subsequent rebound. Low in fasted females, they were poorly, non-significantly suppressed by glucose administration, and no subsequent rebound was observed. Insulin response was hardly impaired in males in respect to females, and neither blood sugar and serum insulin basal levels, nor the rate of glucose disappearance from blood depended upon sex.

Influence of testosterone on blood sugar, serum insulin and free fatty acid responses to glucose in normal male dog.

The influence of testosterone propionate chronic treatment on blood sugar, serum immunoreactive insulin and free fatty acid levels of male, normal, fasted, unanesthetized dogs, basally and during an intravenous glucose tolerance test has been studied. Control experiments using uninjected or vehicle-injected dogs were also performed. Blood sugar and serum immunoreactive insulin basal levels were not affected by testosterone propionate and/or its vehicle, but serum free fatty acids basal values were increased. The blood sugar curve during the test observed in the dogs in the three conditions differed little; neither glucose space nor glucose "k" value were affected by treatments. Testosterone administration reduced by 50% the serum immunoreactive insulin peak following glucose load, as compared to vehicle-injected controls. Hyperglycemia and hyperinsulinaemia induced a fall in serum free fatty acid levels in control groups, followed by a recovery period at the end of the test. Either the fall or the recovery were more intense in testosterone-treated dogs than in vehicle-injected controls. Results are discussed, emphasizing that testosterone exerts a moderate "diabetogenic" action in male dog, inasmuch as although it intensely promotes lipid mobilization and moderately reduces the insulin response to glucose, fails to induce any glucose intolerance.

Alterations in blood sugar, serum insulin and circulating free fatty acid responses to glucose load produced in dogs by chloralose anaesthesia.

The effects of chloralose anaesthesia on the BS, serum IRI and circulating FEA responses to glucose in dogs, in the course of glucose tolerance tests were studied. Chloralose induced a moderate glucose intolerance, and abolished both, the insulin response to hyperglycaemia in these animals and the lipolytic response at the end of the test. These effects indicate that chloralose anaesthesia is definitely improper for metabolic studied in experimental biology.

Effects of thyroid-stimulating hormone upon the regulation of serum insulin levels and on the blood sugar and serum free fatty acid responses to insulin [author's transl].

The effect of a chronic treatment with thyroid-stimulating hormone on the blood sugar, serum insulin and free fatty acid responses to exogenous insulin in dogs was studied comparatively. Either before or after thyroid-stimulating hormone treatment, the blood sugar levels were significantly below- and serum immunoreactive insulin above- their respective base line throughout the test. The blood sugar basal value was raised by the treatment, while the blood sugar levels at any time during the test were not affected. Neither were their respective serum insulin values, nor serum insulin base line. The rate of disappearance of exogenous insulin from blood was not affected either, and insulin space was hardly, significantly increased. Hypoglycaemia induced a mobilization of free fatty acids from lipid stores, which was more intense and prolonged after thyroid-stimulating treatment. These results are discussed, emphasizing the weak lipomobilizing effect of thyroid-stimulating hormone in this species, as well as taking into consideration the mild participation of an extra-pancreatic mechanism such as insulin space in the regulation of serum insulin levels in normal dogs as modified by thyroid-stimulating hormone.

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

The effects of short-term (10 days) thyroxine administration (100 micrograms/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 to 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 free fatty acid responses to graded glucose pulses in hypothyroid dogs.

The 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.

Experimental hyperthyroidism in dogs. Evaluation and effects on blood sugar, serum insulin and free fatty acids during glibenclamide infusion test.

The effects of hyperthyroidism on the BS, serum IRI and FFA responses to HB 419 were studied. Hyperthyroidism, induced by l-thyroxine administration, caused an increase in body temperature, respiratory rate, BS, serum FFA and PBI basal levels. Fasting serum cholesterol was reduced, and body weight, basal metabolic and heart rates, as well as basal serum insulin level failed to be affected. The hypoglycaemic response to HB 419 was moderately facilitated by hyperthyroidism, despite of inducing an impairment in the insulin secretory response. Serum FFA profile, similarly shaped in hyperthyroid dogs and in euthyroid controls, was shifted upwards by hyperthyroid condition. Results are discussed.

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

In bitches in anestrus, artificial endometrial sex cycles were induced. Estrus was induced by 17 beta-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 17 beta-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. Extra-pancreatic factors--space of distribution, t1/2 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 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.