Circadian and Seasonal Variations of Plasma Insulin and Cortisol Concentrations in the Syrian Hamster, Mesocricetus Auratus

Circadian rhythms of plasma insulin, Cortisol, and glucose concentrations were examined in scotosensitive (reproductively sensitive to inhibitory effects of short daylengths) and scotorefractory male and female Syrian hamsters (Mesocricetus auratus) maintained on short (LD 10:14) and long (LD 14:10) daylengths. The baseline concentration (mean of all values obtained every 4 hr six times of day) of insulin was much greater in female than in male scotosensitive hamsters kept on short daylengths. These differences in insulin concentration may account for the observed heavy fat stores in female and low fat stores in male scotosensitive hamsters kept on short daylengths. The baseline concentrations of Cortisol were approximately equal in both scotosensitive and scotorefractory males held on short and long daylengths, but were relatively low in females held on short daylengths and especially high in scotorefractory females held on long daylengths.

The plasma concentrations of both cortisol and insulin varied throughout the day in many of the groups tested. However, the variations were not equivalent. The circadian variations of cortisol were similar irrespective of sex, seasonal condition and daylength. Peak concentrations generally occurred about 12 hr after light onset. In contrast, the circadian variations of insulin differed markedly. For example in male hamsters, robust daily variations were found in scotosensitive hamsters held on short daylengths but not on long daylengths and in scotorefractory hamsters held on long daylengths but not on short daylengths. Furthermore, the daily peak occurred during the light in the scotosensitive hamsters and during the dark in the scotorefractory animals. Neither the daily feeding pattern (about 60% consumed during dark) nor the daily variations of glucose concentration varied appreciably with seasonal condition or daylength. They do not appear to determine nor directly reflect the variations in cortisol and glucose concentrations. It is postulated that the daily rhythms of cortisol and insulin are regulated by different neural pacemaker systems and that changes in the phase relations of circadian systems account in part for seasonal changes in body fat stores.     

Plasma Levels of Growth Hormone,Insulin, Sugar and Acetoacetate in Cattle. Diurnal Variations and Responses to Feeding

The fundamental differences between monogastric animals and ruminants as regards the handling of dietary carbohydrates and as regards the relative importance of gluconeogenesis, rise interesting questions as to the factors regulating the secretion of growth hormone and insulin in poly gastric animals.     

Plasma Insulin during Remission in Juvenile Diabetes Mellitus

Three juvenile diabetics in partial remission were studied before and after the recurrence of overt diabetes. The remissions were partial because glucose tolerance never returned to normal. However, it improved sufficiently to cause the discontinuance of insulin therapy for at least four months.The insulin output in response to double glucose tolerance tests was increased during remission. The degree of remission seemed to be related to the magnitude of the insulin response to glucose. In two of the patients the increase was low and the response very slight. The third patient, however, had a delayed hyper-response and his carbohydrate tolerance during the remission was much more improved than those of the other patients.     

The Quantitative Determination of Fibrinogen in Normal Bovine Plasma and in Cows with Inflammatory Conditions

The quantitative determination of fibrinogen in normal plasma and in cows with inflammatory conditions. A rapid method for the quantitative determination of fibrinogen in bovine plasma is described. The method was employed in the determination of normal values in a material consisting of 100 cows and 50 calves and young animals of various ages. The mean value of the groups of cows was approximately 0.550 g/100 ml. For young animals it was somewhat lower and for cows in the last month of gestation moderately higher than in the other groups. The last part of the experiment involves the determination of the fibrinogen and γ-globulin levels in the plasma of 28 hospitalized cows with various inflammatory conditions. Group A in the material contained animals which were clinically cured and Group B animals that died or were killed. Both groups showed a considerable increase in the fibrinogen level. In Group A the mean value fell back to approximately the normal range while in Group B it remained constantly elevated. The sedimentation rate, SR, in human blood is primarily influenced by the fibrinogen content of the plasma. The SR in bovine blood is very low, and the test is therefore of little significance in diagnostic work. In conclusion, the possibility of using the fibrinogen determination in cattle for the same purpose as the SR in human blood is discussed.     

Insulin Antagonist of Pituitary Origin in Plasma of Normal and Diabetic Subjects

Studies on ultrafiltrates of the plasma of normal and diabetic subjects have shown that a polypeptide of similar characteristics to the growth-hormone-derived polypeptide In-G is present in higher concentrations in diabetic subjects, thus indicating a possible role in the pathogenesis of diabetes mellitus. The polypeptide is absent from the plasma of hypophysectomized diabetic patients.     

Direct Action of Insulin on Plasma Membrane ATPase Activity in Human Lymphocytes

LITTLE is known about the effects of insulin on lymphocytes. Helmreich and Eisen¹ concluded that it has insignificant effects, but others^2–5 have made a case for a role in inflammatory and immunological responses. We^6,7 have demonstrated that noradrenaline enhances the uptake of both glucose and potassium by lymphocytes, as does insulin in several tissues. We have associated this action of noradrenaline with a direct effect on membrane adenosine triphosphatase (ATPase) activity⁷. The observation⁸ that insulin bound to ‘Sepharose’ polymers enhances glucose transport while in contact only with the plasma membrane indicated that insulin might have a direct action similar to that of noradrenaline on membrane ATPase. The observations reported here show that insulin stimulates ATPase activity and glucose uptake in the lymphocyte and suggest a relationship between membrane ATPase activity and glucose transport.     

Plasma Testosterone in Cows Related to Day of Gestation and Sex of the Foetus,and Plasma Testosterone Levels Around Parturition

No significant differences in plasma testosterone level were observed between cows carrying a male foetus and cows carrying a female foetus at any ten-day interval from day 35 of gestation until parturition. Reported higher abortion rates for male than for female foetuses would thus appear not to be due to effects of foetal testosterone on the maternal endocrine balance. In spite of a great individual variation in plasma testosterone values at similar stages of gestation, certain trends are evident. From the 35th to the 80th day of gestation the average concentration was 90–100 pg/ml. Later it rose and reached 200 pg/ml on the 180th day, remaining at this level until after partus. During the first day after parturition plasma testosterone fell significantly and stabilized around 120 pg/ml.     

Insulin Regulates Glut4 Confinement in Plasma Membrane Clusters in Adipose Cells

Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin’s effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60–240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.     

The Effect of Concentrate Feeding on Calcium Metabolism and Plasma Gastrin Concentration in Parturient Cows

The effect of concentrate feeding on calcium metabolism was studied in pregnant cows. The concentrate (5 kg/day) was added to the diet about three weeks before expected calving. A control group was fed only hay during the whole dry period. It was earlier observed in sheep that concentrate feeding was followed by a disturbance in calcium homeostasis, but no such disturbances were observed in the cows. The concentrate fed cows consumed 50 % more calcium than the controls and were found to mobilize less calcium from the skeleton immediately after calving. There was no evidence for the theory that the gastro-intestinal hormone gastrin is involved in calcium homeostasis in the parturient cow.     

Total Thyroxine and Free Thyroxine Index in Plasma of Dairy Cows in Relation To Strength of Heat

Total thyroxine (TT4) and free thyroxine index (FT4I) were measured in peripheral plasma of cows. The samples were collected at the time of insemination from 66 cows showing pronounced signs of the heat and from 56 cows showing weak or silent heat. Neither TT4 or FT4I in plasma differed significantly between the two categories of oestrous cows.     

Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women

ContextObesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity.ObjectivesWe compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development.Methods30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression.ResultsSystemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR.ConclusionOur results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.     

Effect of Acipimox on Plasma Lipids and Glucose/Insulin in Pregnant Rats

To determine how a reduction in maternal hypertriglyceridemia during late pregnancy may affect glucose/insulin relationships, pregnant and virgin rats were orally treated with acipimox, a potent antilipolytic agent. In 20-day pregnant rats receiving 80 mg of acipimox, plasma triglycerides (TG), free fatty acids (FFA), and glycerol decreased more than in virgin rats shortly after the drug (up to 7 hours), when compared with animals treated with distilled water, whereas plasma glucose level was unaffected by the treatment in either group of rats. When acipimox was given every 12 hours from day 17 to day 20 of pregnancy, plasma TG, FFA, and glycerol levels progressively increased, whereas they either decreased or did not change in virgin rats receiving the same treatment, with no effect in plasma glucose levels in either group. Fetal body weight was lower than in controls in 20-day pregnant rats that received acipimox for 3 days. On day 20 of pregnancy, 3 hours after receiving acipimox or distilled water, rats received a 2 g glucose/kg oral load and it was found that the change in plasma glucose was similar in both groups, whereas the increase in plasma insulin was greater in pregnant rats treated with acipimox. However, no difference was found in either variable after the oral glucose load in virgin rats receiving acipimox or distilled water. No differences in plasma glucose levels were found after intravenous (IV) administration of insulin in pregnant rats treated or not treated with acipimox. In conclusion, present results show that administration of acipimox during the last days of gestation inhibited lipolysis and decreased fetal weight. Over a short period of time, in pregnant rats, reductions of plasma FFA and TG after acipimox treatment improved the glucose-induced insulin release, but did not seem to have any effect in peripheral insulin resistance.     

Selenium Levels and Glutathione Peroxidase Activity in Blood,Plasma and Reproductive Organs in Dairy Cows

Selenium levels and glutathione peroxidase activity were determined in blood and reproductive organs in 12 Norwegian dairy cows at different stages of the oestrus cycle. Blood samples were collected before slaughter, and samples from genital organs were obtained as soon as possible after slaughter. Blood and plasma selenium levels were significantly correlated with selenium levels in follicular fluid, and in ovarian and uterine tissues, but not with the levels in corpora lutea. The activity of blood glutathione peroxidase was significantly correlated with that in ovarian and uterine tissue, but not with activity in corpora lutea and follicular fluid. No effect of stage of oestrus cycle on selenium content or glutathione peroxidase in reproductive tissue was observed.     

Circadian and Ultradian Rhythms in Blood Glucose and Plasma Insulin of Healthy Adults

The circadian and ultradian variations of blood glucose and plasma insulin have been characterized individually and as a group phenomenon in five healthy young adults studied while adhering as closely as possible to their usual routine of sleep, activity, meal content and timing. Three complementary methods were used to analyze the data: displaying raw data as a function of time; cosinor method according to Nelson and Halberg; and time series analyses as proposed by De Prins and Malbecq. The subjects were studied in the laboratory and their life routine were controlled, but very close to that of their habitual routine. They had mainly ultradian rhythms of blood glucose (mainly about 6 hr) and circadian rhythms of immunoreactive insulin (I.R.I.). Blood glucose ultradian rhythms seem to be mainly but not exclusively mealtime dependent, while I.R.I, circadian rhythms appear to be primarily endogenous in origin. Therefore, the role played by insulin in the control of blood glucose levels seems to be programmed on a circadian basis rather than by a time independent feedback phenomenon as postulated by the conventional homeostatic hypothesis. The advantage of this chronophysiologic approach is to consider circadian rhythms of both I.R.I. and insulin effectiveness as an adaptive phenomenon able to maintain blood sugar changes in the ultradian domain of rhythms.