Growth hormone and somatostatin in the plasma of transiently diabetic ducks: basal variation and response to glucose.

In the duck, subtotal pancreatectomy induces a transient diabetes, with decreased insulin and glucagon basal levels as well as responses to glucose. At the same time, a transient increase in basal peripheral somatostatin occurs, followed by an increase in growth hormone in the postdiabetic state. Intravenous glucose induces a slight decrease in somatostatin secretion in normal, but not in diabetic animals, and no significant variation in growth hormone secretion at any state. An obvious role of growth hormone or somatostatin in the development of this transient diabetes in the duck could not be detected in this study.

Somatostatin-like immunoreactivity in duck plasma, hypothalamus and neural lobe during post-hatch growth: comparison with plasma and pituitary growth hormone concentrations.

Variations in the concentrations of plasma and pituitary GH were determined in ducks for 66 and 87 days after hatch, and compared with somatostatin-like immunoreactivity (SLI) in the plasma, hypothalamus and neural lobe. Plasma GH levels gradually decreased during growth, while pituitary GH content increased. The concentration of pituitary GH increased during the first 3 weeks of age and remained relatively constant thereafter. The decline in plasma GH concentration was paralleled by a similar fall in the level of plasma SLI. While the content of hypothalamic SLI increased during development, the SLI concentration was maximal at 14 days of age and lowest in adults. The content and concentration of SLI in the neural lobe, in contrast, increased progressively during development. Gel filtration of hypothalamic and neural lobe extracts demonstrated that both young and older birds had two main peaks of SLI, corresponding to somatostatin-14 and somatostatin-28, and a third, larger form. The elution pattern of plasma SLI was similar in young and older birds and was principally composed of a large molecular species ('big' somatostatin), although an additional small peak eluting between somatostatin-28 and somatostatin-14 was eluted from a large pool of plasma from 90-day-old ducks. These results suggest that increased plasma GH levels in young birds do not result from a hypothalamic somatostatin deficiency nor from variations in molecular forms of SLI, and that the age-related decline in plasma GH concentration is not due to a deficiency in pituitary GH content. The decline in the circulating GH level during growth is probably due to an increase in hypothalamic somatostatin release.

Pancreatic somatostatin, glucagon and insulin during post-hatch growth in the duck (Anas platyrhynchos).

Pancreatic somatostatin-like immunoreactivity (SLI), immunoreactive insulin (IRI) and glucagon-like immunoreactivity (GLI) were measured during growth in ducks. The content of each hormone increased progressively but at different rates in the dorsal, ventral and splenic lobes of the pancreas. In the almost fully grown duck, the splenic lobe contained 80 and 63% of the total content of GLI and SLI respectively but low levels of IRI (23%), which were highest in the dorsal lobe (53%). In contrast to the hormonal content, only total GLI concentrations increased during development, the SLI concentrations remaining stable and IRI concentrations declining during growth. Gel filtration of pancreatic extracts indicated that most of the SLI in the pancreas of young and adult birds was somatostatin-14, although somatostatin-28 was present in the ventral lobe of young birds and larger molecular forms were present in the ventral and dorsal lobes. These changes in pancreatic hormonal content and concentration are dissimilar to age-related changes in SLI, GLI and IRI previously observed in the plasma of ducks. Plasma levels of pancreatic hormones may thus be controlled by hormonal and/or neutral factors during post-hatch growth.

Control of plasma levels of growth hormone, glucagon and insulin in ducklings: roles of free fatty acids and somatostatin.

The effects of plasma free fatty acids (FFA) and somatostatin-14 (S-14) on concentrations of plasma GH, glucagon and insulin were investigated in juvenile ducks. Oleic acid, S-14 or both were infused into 4- to 7-week-old birds and plasma GH, glucagon-like immunoreactivity (GLI), immunoreactive insulin (IRI) and FFA were measured. An increase in plasma GH and a decrease in GLI but no change in IRI was observed after infusion of 9 mg oleic acid/kg per min. A decrease in plasma GH, FFA and IRI and an increase in plasma GLI was seen after infusion of 800 ng S-14/kg per min. These effects of S-14 on IRI and GLI were abolished when S-14 was infused simultaneously with oleic acid. It is concluded that FFA have a direct stimulatory effect on GH secretion and an inhibitory effect on glucagon secretion. Somatostatin-14 directly inhibits the secretion of GH and its stimulatory effect on the secretion of glucagon is mediated by a depression in concentrations of plasma FFA. Finally, S-14 has no effect on plasma insulin when basal levels of plasma FFA are maintained.

Growth hormone secretion and pancreatic function following somatostatin infusion in ducks (Anas platyrhynchos).

The intravenous infusion of somatostatin (800 ng/kg min) reduced the concentration of growth hormone (GH) in the plasma of 4 to 5, 6 to 7 and 8 to 9 week-old ducklings, but not in adult ducks. The inhibition of GH secretion was not due to accompanying changes in pancreatic function, since the infusion of a lower dose of somatostatin (200 ng/kg min) increased glucagon release and decreased plasma free fatty acids (FFA), as observed with the higher dose, but had no effect on GH concentrations. The withdrawal of somatostatin inhibition resulted in rebound GH secretion in immature birds, the magnitude of which was directly related to the pre-treatment level. Following somatostatin infusion (800 ng/kg min) no modification in GH concentration was observed in adult ducks. These results demonstrate that basal GH release in young birds is not autonomous and is suppressible by somatostatin. The data provide further evidence for age-related changes in the control of avian GH and insulin release and for the independence of the effects of somatostatin on the pituitary and pancreas glands.

Comparative effects of somatostatin-28 and somatostatin-14 on basal growth hormone release and pancreatic function in immature ducks (Anas platyrhynchos).

The 30-min infusion of somatostatin (SRIF)-14 or SRIF-28 (800 ng/kg/min) in 7- to 8-week-old ducklings reduced the basal level of plasma growth hormone (GH). The magnitude of the GH suppression induced by SRIF-14 was similar to that elicited by SRIF-28. "Rebound" GH secretion was observed 30 min after infusion, the GH concentration being elevated above the basal level. The increase in GH secretion after SRIF-14 infusion was greater than that induced by SRIF-28. Plasma insulin and free fatty acid (FFA) levels were similarly reduced after 10 and 30 min of SRIF-14 or SRIF-28 infusion. Following infusion the FFA levels returned to the pretreatment concentration, whereas the insulin concentration in both groups remained suppressed 30 min after infusion. The insulin level was still suppressed 60 min after SRIF-14 infusion, but not after SRIF-28 infusion. The infusion of SRIF-14 resulted in a marked, progressive increase in the glucagon concentration, which was reduced in birds infused with SRIF-28 and accompanied by hypoglycaemia. Following SRIF-28 infusion a "rebound" in the glucagon concentration occurred and remained elevated for at least 60 min. These results demonstrate comparative effects of SRIF-14 and SRIF-28 on the basal release of pituitary GH and pancreatic insulin and glucagon, and in particular they suggest that SRIF-28 is more potent in inhibiting pancreatic A cell activity.

Influence of insulin and glucagon on secretion of growth hormone in growing ducks (Anas platyrhynchos).

An inverse age-related pattern of GH secretion has been identified in immature ducks between 2 and 9 weeks of age, the plasma level of GH falling progressively from 30-40 ng/ml at 2 weeks of age to the adult level (less than 10 ng/ml) by 9 weeks of age. This decrease in GH secretion was not accompanied by any age-related changes in the concentrations of plasma immunoreactive insulin of glucagon-like immunoreactivity or in plasma glucose or free fatty acid level. In 4- to 6-week-old ducklings the intravenous infusion of insulin (2.5 or 10 mu./kg per min for 30 min) and glucagon (0.1 or 0.5 micrograms/kg per min for 30 min) induced some inhibition of GH secretion, independently of changes in blood glucose level. These results suggest that although insulin and especially glucagon have direct effects on GH secretion in the duck, maturational differences in pancreatic function are unlikely to be causally related to the decrease in GH secretion during growth.

Pituitary and adrenal control of pancreatic endocrine function in the duck. III. Effects of glucose, oleic acid, arginine, insulin and glucagon infusions in hypophysectomized or normal ducks.

The existence of plasma metabolites (glucose, free fatty acids [FFA[, aminoacids [AA])--pancreatic hormones (insulin, glucagon) feedback mechanisms and of insulin-glucagon relationships were studied in hypophysectomised ducks; the insulinogenic effect of glucagon was also studied in normal ducks in physiological conditions. Glucose infusion stimulated insulin secretion in hypophysectomised ducks; during oleic acid infusion, plasma IRI (immunoreactive insulin) was not modified whereas plasma GLI (glucagon like immunoreactivity) level drops slightly. Arginine induced insulin and glucagon secretion. Plasma GLI did not decrease during insulin infusion. In normal ducks glucagon was insulinogenic, hyperglycaemic and hypoaminoacidaemic. These biological properties of glucagon were lost in hypophysectomised ducks, except the effect on plasma aminoacids. It is concluded that the anterior pituitary and the adrenal cortex indirectly control the endocrine function of the pancreas, via the plasma metabolites and the insulin-glucagon interactions. In normal ducks, glucagon is probably insulinogenic in physiological conditions.

Pituitary and adrenal control of pancreatic endocrine function in the duck. II. Plasma free fatty acids, aminoacids, and insulin variations following hypophysectomy and replacement therapy with growth hormone and corticosterone.

The levels of plasma free fatty acids, aminoacids and insulin were studied in normal, hypophysectomized and beef growth hormone and/or corticosterone treated hypophysectomized ducks. Hypophysectomy decreased plasma free fatty acids, aminoacids and insulin levels; growth hormone and growth hormone + corticosterone treatments in hypophysectomized animals induced opposite changes, while corticosterone alone only increased the concentrations of plasma aminoacids and insulin. However, corticosterone enhanced the growth hormone effects on the three parameters. It is suggested that four feed-back mechanisms may be involved in the control of glucagon secretion by the anterior pituitary and the adrenal cortex : glucose-glucagon, free fatty acids-glucagon, aminoacids-glucagon and insulin-glucagon. In addition, in these experiments, insulin and glucagon always varied in opposite directions.

Pituitary and adrenal control of pancreatic endocrine function in the duck.

Recent clinical and immunological data suggest that the classical concept of "idiopathic autoimmune diseases" is to be revised. In a normal population, autoimmunity reactions against thyroid gland, gastric mucosa and adrenals develop slowly with increasing age and are found more frequently in women than in men (at least so far as thyroid antibodies are concerned) as is lowering of the functional activity of T lymphocytes. Diabetes takes its place among a series of factors diminishing immunocyte reactivity, and thus enhancing the development of the autoimmunity process. This may perhaps be promoted in some way by genetic factors, perhaps those which also play a definite though as yet ill-defined role in determining the emergence of diabetes. For the present, diabetes mellitus itself must only rarely be considered a consequence of an autoimmune process and then only in certain insulin-dependent cases. By contrast, diabetes appears frequently to be an activator of autoimmune phenomena against tissues other than pancreas, namely thyroid gland, adrenals and gastric mucosa. Awareness of these associations should encourage physicians to seek latent humoral or cellular evidence of autoimmune phenomena in diabetics; this would favour the early recognition of clinically important abnormalities which may accompany the diabetes.