Insulin secretion from pancreatic islets: Effect of growth hormone and related proteins

Abstract

Insulin responses to clinical grade human growth hormone (hGH), intact hGH, naturally occurring diabetogenic substance (NDS), and subtilisin cleaved forms of hGH (S1 and S3) were studied using hypophysectomized rat pancreatic islets. While clinical grade hGH (200 microgram/ml) elicited a prompt and sustained release of insulin, purified intact hGH (200 microgram/ml) did not. Naturally occurring diabetogenic substance, isolated from clinical grade hGH preparations, stimulated insulin release at 200 ng/ml. Upon repeat stimulation with NDS, a significantly greater insulin release than with initial stimulation was observed. Although S3 (200 microgram/ml) elicited significant insulin release, S1 (200 microgram/ml) did not. Direct stimulation of insulin release with clinical grade hGH is not due to intact hGH but another proteins(s) such as NDS. Enzymic modification of intact hGH appears to enhance insulin stimulatory capacity.

Direct effects of rat growth hormone on rat islets of Langerhans in tissue culture

“…By contrast, when growth hormone is incubated with isolated islets in vitro for up to three hours, it has been shown that there is no direct stimulation of insulin release [4,9,10,11]. This confirms studies using pancreatic pieces or whole pancreatic peffusion [4,9,12,27], although here the acute stimulation of insulin release by GH has also been reported [13,28,29].…”

“…Furthermore, a factor closely associated with growth hormone, but not identical with it, may also stimulate insulin release in per• islets of hypophysectomised rats, while purified, intact, human GH will not [11]. In the light of these observations the question also arises as to whether or not growth hormone is being modified in the tissue culture to a more biologically active material.…”

Different Acute in vivo Effects of Bacterial Derived and Pituitary Growth Hormone Preparations on Plasma Levels of Glucagon, Insulin and Free Fatty Acids in Rabbits

“…4, 5). A variety of fac tors have been demonstrated in pituitary' growth hormone preparations such as lipotropin, a human lipid-mobilizing factor (LMF), neurophysin, an insulotropin and diabetogenic substances [2,14,16,17,19,30,31]. The constituents observed in Cres cormon® on SDS electrophoresis migrated with a similar mobility to parts of the LMF 2 fraction (fig.…”

“…However, there are reports indicating that growth hormone does not stimulate glucagon secretion [5] and that the insulin-releasing properties of growth hormone preparations arc due to a naturally occurring diabetogenic substance and to subtilisin-cleaved forms of growth hormone [19]. There are also contradictory reports whether growth hormone is a lipolytic hor mone in rats [8.…”

“…Various metabolic actions on carbohydrate, protein and fat me tabolism have been attributed to human growth hormone [23]. It has been shown that some metabolic actions of growth hormone preparations, such as the lipid-mobilizing [6,30], diabetogenic [31] and insulin-releasing effects [19] may partly or entirely be due to other pituitary polypeptides. On the other hand, growth-promoting, lactogenic, hyper glycemic and insulin secretagogic activities are enhanced by posttranslational proteolytic cleavage of growth hormone, suggesting that growth hormone may be a prohormone [21].…”