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The results of serial glucose tolerance tests in cortisol-treated, thyroidectomized calves indicate that there is a progressive reduction in the tolerance to glucose and that this is associated with a diminution in the rise in plasma insulin concentration which normally occurs in response to hyperglycaemia. These experimental conditions also stop growth within 12–14 days. All these effects are reversed by injections of thyroxine at a dose which raises the plasma thyroxine concentration to normal values for 7 days in spite of the continued administration of cortisol.

These results suggest that, in the unweaned thyroidectomized calf, daily injections of cortisol reduce the sensitivity of the insulin release mechanism, which may provide an explanation for the severe diabetic syndrome which is known to develop under these conditions.

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Primed continuous intraruminal infusions of tracer amounts of [2-14C]propionate were used to measure propionate production and the incorporation of propionate carbon into glucose by six sheep on a diet of 1000 g chopped hay/day. Primed continuous intravenous infusions of [U-14C]glucose were used to measure the rate of glucose entry in the same sheep. The measurements were repeated 24 h after a single intramuscular injection of betamethasone.

Maximum hyperglycaemia and a significant increase in glucose entry occurred after 24 h but there was no significant change in propionate production or in the synthesis of glucose from propionate.

It is concluded that the increase in glucose entry must arise from substrates other than propionate such as amino acids.

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Metabolic fuels play an important role in the regulation of growth hormone secretion. Hypoglycaemia increases plasma growth hormone (GH) concentrations while hyperglycaemia has a suppressive effect (Roth, Glick, Cuatrecasas & Hollander, 1967). Amino acid infusions have been reported to increase plasma GH, although recent evidence suggests that this effect may be non-specific (Best, Catt & Burger, 1968). Elevated plasma free fatty acids (FFA) have no effect on plasma GH concentrations (Schalch & Kipnis, 1965), whereas depression of plasma FFA by nicotinic acid has been shown to enhance GH secretion (Irie, Sakuma, Tsushima, Shizume & Nakao, 1967). The effect of ketones on plasma GH concentrations has not been studied. As many of the stimuli for GH secretion such as hypoglycaemia, 2-deoxyglucose administration, exercise, starvation, and surgical and psychic stress produce hyperketonaemia, a possible role for ketones in the regulation of GH secretion was investigated.

Eight rhesus monkeys were anaesthetized with sodium

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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.

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Effect on the foetus of diabetic diathesis in the mother


Energy metabolism and hormonal status

Normal newborn infant

Infant of diabetic mother:

Blood glucose and free fatty acids



Growth hormone

Synalbumin antagonist

Adrenal cortex

Adrenal medulla

High perinatal mortality

Congenital abnormalities

Later incidence of clinical diabetes

The diabetogenic effect of pregnancy on the mother

Changes in glucose tolerance in normal pregnancy; criteria of normality; diagnosis of prediabetes

Plasma insulin in normal pregnancy

Glucose tolerance and plasma insulin in gestational diabetes

Parity and the development of diabetes


The subject of pregnancy and diabetes can be considered from two main points of view: that of the baby and that of the mother.

There is no doubt that the children born to diabetic mothers (both before and after the development of clinical diabetes) commonly exceed the mean body weight for their gestational age, have a characteristic appearance,

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P. E. B. REILLY and E. J. H. FORD


Primed continuous infusions of tracer amounts of [U-14C]glucose and of [U-14C]labelled mixed amino acids were used to measure plasma glucose and amino acid entry rates and to obtain an index of the incorporation of amino acid carbon into glucose by sheep before and 24 h after a single intramuscular injection of betamethasone.

Maximum hyperglycaemia occurred 24 h after administration of the steroid, but there was no significant change in arterial amino acid concentration. Mean glucose entry rate was significantly raised 24 h after steroid administration. The rate of incorporation of amino acid carbon into glucose also increased significantly. The increases in plasma glucose concentration and in glucose entry confirm the authors' previous results. The results also indicate that a significant proportion of the additional glucose entry is synthesized from amino acid carbon.

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Several amino acids have been shown to stimulate insulin release from the pancreatic β-cell (Fajans, Knopf, Floyd, Power & Conn, 1963; Fajans, Floyd, Knopf & Conn, 1967). Although the various amino acids act directly on the β-cell there is some evidence that in the normal post-prandial state synergism occurs with various alimentary factors (Jarrett, Graver & Cohen, 1969). In this respect amino acids play a similar role to glucose after ingestion of a meal. The rise in both glucose and aminoacid levels stimulates insulin release and the insulin causes an increased uptake of glucose and amino acids by the tissues. In both instances other hormonal and alimentary factors may influence the effect of the metabolite on the β-cell.

There is evidence that the secretion of insulin in response to hyperglycaemia is impaired in the newborn infant (Baird & Farquhar, 1962). Since insulin plays an important role in tissue growth it

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It has been reported that hypoglycin and hypoglycin-like compounds, including 4-pentenoic acid, inhibit fatty acid oxidation and gluconeogenesis as well as inducing profound hypoglycaemia (Bressler, Corredor & Brendel, 1969). A vinyl group separated by two carbon atoms from the carboxyl group is apparently a structural requirement for biological effects (Corredor, Brendel & Bressler, 1967), valeric acid, the saturated analogue of 4-pentenoic acid, being inactive. In the course of investigations on insulin secretion in ruminants we observed that valerate is a very potent insulin secretogogue (Horino, Machlin, Hertelendy & Kipnis, 1968). In this communication evidence is presented which shows that 4-pentenoic acid is also a potent stimulant of insulin secretion in the sheep and, contrary to observations in non-ruminants, it can induce hyperglycaemia and inhibit lipolysis.

Four castrated male sheep (35–50 kg) were infused through a polyethylene catheter inserted into a jugular vein after a 24-h fast. Two animals received I

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In mammals, neurohypophysial hormones play a physiological role in the regulation of the metabolism of water and influence the contractility of certain smooth muscles. They may also produce hyperglycaemia (see Waring & Landgrebe, 1950; Mirsky, 1963; Cash & Kaplan, 1964). It is not known whether this response is of physiological significance. A hyperglycaemic effect has also recently been shown when the homologous neurohypophysial hormone, arginine vasotocin, is injected into lampreys (Cyclostomata) and toads (Amphibia) (Bentley & Follett, 1965; Bentley, 1965) and when oxytocin is given i.v. to chickens (Kook, Cho & Yun, 1964). The neurohypophysis of the chicken (Gallus domesticus) contains oxytocin, and vasotocin is also present but at five times greater concentration (Munsick, Sawyer & van Dyke, 1960; Heller & Pickering, 1961). Vasotocin is much more active than oxytocin in producing antidiuresis and contraction of the oviduct in this species (Munsick et al. 1960). The present study confirms the

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Since Cushing [1932] described the syndrome of pituitary basophilism (Cushing's syndrome) many cases of the condition have been published. The syndrome is characterized by an obesity sparing the limbs, by marked hypertension, glycosuria and hyperglycaemia, osteoporosis, characteristic cutaneous striae, polycythaemia, amenorrhoea and hypertrichosis in the female, impotence in the male, asthenia and diminished resistance to infection [Cohen & Dible, 1936]. Pathological findings in the condition have been very varied in cases which have been clinically indistinguishable (see Crooke's [1935] series). By 1936 the following abnormalities had been described: basophil adenoma and basophilia (relative increase of pituitary basophil cells); adreno-cortical hyperplasia, adenoma, carcinoma; and thymic carcinoma associated with adreno-cortical hyperplasia. In a few cases neither adreno-cortical, thymic, nor anterior pituitary tumours were recorded [Oppenheimer, Globus, Silver & Shaskin, 1935; Freyberg, Barker, Newburgh & Coller, 1936; Crooke, 1935; Cohen & Dible, 1936].

It seemed remarkable that such diverse pathological findings should be