Progesterone decreases the oxidation of 2-deoxyglucose and glucose through the pentose-phosphate pathway in isolated female rat adipocytes and, therefore, the effect of this steroid on the activity of the phosphorylating enzyme, hexokinase, was studied. After a 30-min incubation in vitro, progesterone decreased total hexokinase activity but did not affect the isoenzyme-I activity. Progesterone had no direct effect on fat cell cytosol hexokinase and its action on glucose oxidation was not affected by variations in the concentration of Mg2+, the cofactor of hexokinase. Our data suggest that the decreased activity of hexokinase in the presence of progesterone is due to a decrease in the activity of the insulin-sensitive isoenzyme-II. This results from the steroid acting at a step beyond enzyme activation and may be mediated by a feedback mechanism.
M.-Th. Sutter-Dub and M.-Th. Vergnaud
A. P. F. FLINT
Progesterone in vitro decreases the rates of glucose uptake and of acetate uptake and oxidation, of lipogenesis from acetate and of oxygen consumption, and reduces the intracellular concentrations of ATP and citrate in slices of luteinized rat ovary incubated in a bicarbonate-buffered medium. The effect on glucose uptake was shown to be due to inhibition by progesterone of the membrane transport of glucose. In view of the steroid concentrations used to elicit these effects in vitro and the known actions of steroids such as progesterone on biological membranes, these observations are thought to be due to non-physiological lytic effects.
J. M. BASSETT
Some metabolic effects of cortisol were investigated in non-pregnant ewes fed either ad lib. or on a restricted ration.
Cortisol (25 mg./day) administered for a period of 21 days stimulated the voluntary food intake of fat ewes offered food ad lib. Higher levels of cortisol (50 and 75 mg./day) administered for similar periods subsequently had little additional effect on voluntary food intake, but an even greater cortisol dose (150 mg./day) resulted in a marked decline in voluntary food intake. Ewes fed a constant restricted ration did not refuse food at any time during cortisol administration.
Urinary nitrogen excretion was increased during cortisol administration but sequential increases in the cortisol dose failed to increase urinary nitrogen excretion proportionately above the level attained during administration of 25 mg. cortisol/day.
The blood glucose level was elevated progressively as the level of cortisol administered was increased. Similarly, tolerance for a glucose load was impaired progressively.
Only very small changes in blood ketones and plasma free fatty acid levels were observed during cortisol administration.
The changes in blood glucose during cortisol administration cannot be accounted for by changes in gluconeogenesis, and it is suggested that they reflect a progressive impairment of glucose utilization relative to the blood glucose level, though not a reduction in total glucose utilization.
R. L. REID and N. T. HINKS
The effects of insulin, glucose injection and oral glycerol on blood or plasma levels of glucose, free fatty acids (FFA), acetic acid and ketone bodies have been studied in alloxan-diabetic sheep. Insulin (0·5 i.u./kg.) lowered glucose levels only slightly, but induced a prompt and marked fall in FFA and acetate levels; ketones declined steadily after the first hour. The rate of utilization of injected glucose was considerably slower in diabetic than in non-diabetic sheep. FFA levels did not decline after glucose injection, while acetate levels declined slowly. Ketone levels were not affected significantly. Glycerol (180 ml.) per os reduced acetate and ketone levels, while tending to increase FFA values. Blood glucose also increased considerably. These data are consistent with present knowledge of the metabolic lesions in severe diabetes. However, it is concluded that there is impairment of acetate and, probably, ketone oxidation in severe diabetic ketosis. Finally, the metabolic changes recorded are compared with those which occur after insulin, glucose or glycerol administration to ewes showing clinical signs of ovine pregnancy toxaemia following severe and prolonged undernourishment in late pregnancy.
L Morgan, J Arendt, D Owens, S Folkard, S Hampton, S Deacon, J English, D Ribeiro and K Taylor
This study was undertaken to determine whether the internal clock contributes to the hormone and metabolic responses following food, in an experiment designed to dissociate internal clock effects from other factors. Nine female subjects participated. They lived indoors for 31 days with normal time cues, including the natural light: darkness cycle. For 7 days they retired to bed from 0000 h to 0800 h. They then underwent a 26-h 'constant routine' (CR) starting at 0800 h, being seated awake in dim light with hourly 88 Kcal drinks. They then lived on an imposed 27-h day (18 h of wakefulness, 9 h allowed for sleep), for a total of 27 days. A second 26-h CR, starting at 2200 h, was completed. During each CR salivary melatonin and plasma glucose, triacylglycerol (TAG), non-essential fatty acids (NEFA), insulin, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured hourly. Melatonin and body temperature data indicated no shift in the endogenous clock during the 27-h imposed schedule. Postprandial NEFA, GIP and GLP-1 showed no consistent effects. Glucose, TAG and insulin increased during the night in the first CR. There was a significant effect of both the endogenous clock and sleep for glucose and TAG, but not for insulin. These findings may be relevant to the known increased risk of cardiovascular disease amongst shift workers.
C G Walker, M C Sugden, G F Gibbons and M J Holness
). Adipocyte glucose metabolism ex vivo under ‘fasting’ conditions We incubated isolated EPI adipocytes with low glucose and in the absence of insulin to mimic the fasting extracellular milieu. Absolute rates of glucose oxidation to CO 2 by
M. GRIFFITHS, D. L. McINTOSH and R. M. C. LECKIE
Alloxan diabetes can be induced in red and in grey kangaroos and the initial changes in blood sugar levels after injection of the drug are similar to those in other herbivores, or in other vertebrates generally.
In general the presence or absence and the severity of catabolic effects of diabetes in rabbits, sheep and red kangaroos all eating the same diet depends on the amount of food eaten.
Injection of large amounts of cortisone into normal rabbits and a sheep induced the usual catabolic effects and injection of cortisone exacerbated the catabolism of diabetic rabbits and diabetic sheep. The same and larger dose rates of cortisone injected into 12 normal and two diabetic red kangaroos had no effect on N balance, hyperglycaemia, food intake, glycosuria, insulin sensitivity, or on intravenous glucose tolerance.
SJ Fisher, ZQ Shi, HL Lickley, S Efendic, M Vranic and A Giacca
At supraphysiological levels, IGF-I bypasses some forms of insulin resistance and has been proposed as a therapeutic agent in the treatment of diabetes. Unfortunately, side effects of high-dose IGF-I (100-250 microg/kg) have precluded its clinical use. Low-dose IGF-I (40-80 microg/kg), however, shows minimal side effects but has not been systematically evaluated. In our previous study under conditions of declining glucose, low-dose IGF-I infusion was more effective in stimulating glucose utilization, but less effective in suppressing glucose production and lipolysis than low-dose insulin. However, under conditions of hyperglycemia, we could not observe any differential effects between high-dose infusions of IGF-I and insulin. To determine whether the differential effects of IGF-I and insulin are dose-related or related to the prevailing glucose level, 3 h glucose clamps were performed in the same animal model as in the previous studies, i.e. the moderately hyperglycemic (175 mg/dl) insulin-infused depancreatized dog, with additional infusions of low-dose IGF-I (67.8 microg/kg, i.e. 29.1 microg/kg bolus plus 0.215 microg/kg( )per min infusion; n=5) or insulin 49.5 mU/kg (9 mU/kg bolus plus 0.45 mU/kg per min; n=7). As in the previous study under conditions of declining glucose, low-dose IGF-I had significant metabolic effects in vivo, in our model of complete absence of endogenous insulin secretion. Glucose production was similarly suppressed with both IGF-I and insulin, by 54+/-3 and 56+/-2% s.e. (P=NS) respectively. Glucose utilization was stimulated to the same extent (IGF-I 5.2+/-0.2, insulin 5.5+/-0.3 mg/kg per min, P=NS). Glucagon, free fatty acid, glycerol, alanine and beta-hydroxybutyrate, were suppressed, while lactate and pyruvate levels were raised, similarly with IGF-I and insulin. We conclude that: (i) differential effects of IGF-I and insulin may be masked under hyperglycemic conditions, independent of the hormone dose; (ii) low-dose IGF-I has no selective advantage over additional insulin in suppressing glucose production and lipolysis, nor in stimulating glucose utilization during hyperglycemia and subbasal insulin infusion when insulin secretion is absent, as in type 1 diabetes mellitus.
Anthony J Weinhaus, Laurence E Stout, Nicholas V Bhagroo, T Clark Brelje and Robert L Sorenson
PRL have increased glucose metabolism ( Weinhaus et al. 1996 ). In addition, the elevated insulin secretion can be accounted for solely in terms of their increased rates of glucose oxidation ( Weinhaus et al. 1996 , 1998 ). In β-cells, the rate
Daniel Simões, Patrícia Riva, Rodrigo Antonio Peliciari-Garcia, Vinicius Fernandes Cruzat, Maria Fernanda Graciano, Ana Claudia Munhoz, Marco Taneda, José Cipolla-Neto and Angelo Rafael Carpinelli
) has a significant role in the process of insulin secretion, negatively regulating GSIS in pancreatic islets and modulating glucose metabolism ( Morgan et al. 2009 , Rebelato et al. 2011 ). Briefly, NOX consists of two membrane-bound subunits, gp91