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

Whittaker, P. G.; Taylor, K. W.

doi:10.1007/bf00251014

Cited by 24 publications

(13 citation statements)

References 28 publications

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“…The concomitant stimulation of plasma insulin and glucose concentrations during GH administration was consistent with earlier observations that GH has a direct stimulatory effect on insulin secretion (Whittaker & Taylor, 1977), but that it also causes insulin resistance. This latter phenomenon is well documented in man, where human GH causes insulin resistance at two levels, at the hepatic level where it impairs the ability ofinsulin to suppress glucose production (Hansen, Tsalikian, Beaufrere et al 1986) and at the extrahepatic level where it impairs the insulin-mediated glucose utilization by peripheral tissues (Rizza, Mandarino & Gerich, 1982;Rosenfeld, Wilson, Dollar et al 1982).…”

Section: Discussionsupporting

confidence: 91%

Influence of protein nutrition on the response of growing lambs to exogenous bovine growth hormone

MacRae¹,

Bruce²,

Hovell³

et al. 1991

Journal of Endocrinology

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Interactions between protein supply and the anabolic response to exogenous bovine (b) GH have been examined in two experiments using 28-35 kg lambs sustained entirely by intragastric infusion of volatile fatty acids (700 kJ/kg W 0.75 per day) into the rumen and the casein (600 mg (low protein; LP) or 1200 mg (high protein; HP)/kg W 0.75 per day) into the abomasum. Sheep received continuous i.v. infusions of bGH for 6 days in experiment 1 and for 18 days in experiment 2. Nitrogen balances were determined daily throughout both experiments and blood samples, from indwelling catheters, were assayed for GH, insulin-like growth factor-I (IGF-I), insulin and glucose. Infusion of bGH increased plasma GH concentration by five- to sixfold in all animals. There was an increase in N retention in both HP and LP animals over the first 2-3 days of GH administration. HP animals sustained higher N retentions (31%; P less than 0.05) throughout the GH administration but LP animals did not. In contrast, plasma IGF-I concentrations increased progressively over the first 72 to 96 h of GH administration in all sheep and thereafter remained significantly (P less than 0.05) elevated until termination of the GH infusion. In lambs which received both HP and LP infusion in experiment 1 the increase in IGF-I and LP infusions in experiment 1 the increase in IGF-I concentration by day 6 of GH administration was significantly (P less than 0.05) greater when they received the higher protein intake.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionsupporting

confidence: 91%

Influence of protein nutrition on the response of growing lambs to exogenous bovine growth hormone

MacRae¹,

Bruce²,

Hovell³

et al. 1991

Journal of Endocrinology

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“…However it is unlikely that such an effect can explain the enhancing effect of growth hormone on insulin secretion since in the hypophysectomised group the effect of growth hormone addition was actually to lower somewhat the cyclic AMP content. It has previously been reported that basal adenyl cyclase activity in rat islets is unaffected by culture for 16h with growth hormone although total adenyl cyclase was increased [21].…”

Section: Resultsmentioning

confidence: 89%

Effects of hypophysectomy and growth hormone on cultured islets of Langerhans of the rat

Pierluissi

Ashcroft

1982

Diabetologia

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Summary. The effects on islet function of addition to the culture medium of rat growth hormone was studied in 4-day cultured islets of Langerhans from normal and hypophysectomised rats. In islets from hypophysectomised rats, rates of insulin release were 34% lower than in control rat islets; rates of insulin plus proinsulin and total protein biosynthesis were also lower by 48% and 16% respectively. The rates of glucose oxidation and the islet content of cyclic AMP were unchanged in islets from hypophysectomised rats but the islet content of calmodulin was decreased by 68%. The presence of rat growth hormone during the culture period restored the secretory response of hypophysectomised rat islets to that seen in control islets cultured without growth hormone but had only a marginal effect on the rate of insulin plus proinsulin biosynthesis, and no significant effect on islet calmodulin content. Glucose oxidation was increased by the presence of growth hormone during the culture period in both control (73% increase) and hypophysectomised (38% increase) rat islets. Addition of growth hormone to the culture medium also enhanced rates of insulin release and biosynthesis in control islets by 116% and 20% respectively. It is suggested that these changes arise primarily from modification of the synthesis of specific islet proteins.Key words: Insulin release, insulin biosynthesis, growth hormone, calmodulin, cyclic AMP, islet glucose metabolism, hypophysectomy, cultured islets.Insulin secretion is subject to acute regulation by nutrients such as glucose and amino-acids and by hormones such as glucagon. In addition B-cell secretory * Present address: Department of Physiology, Vargas School of Medicine, Central University of Venezuela, Caracas, Venezuela function is influenced chronically by experimental manipulations such as starvation [1] or hypophysectomy [2][3][4][5], and in pregnancy [6]. We have shown that the impaired insulin secretory response of islets from hypophysectomised rats persists following 4-day culture of the islets and may be reversed by the addition of growth hormone to the culture medium [2]. To investigate the mechanisms involved, we have measured other parameters of islet function in normal and hypophysectomised rat islets cultured in the absence or presence of rat growth hormone. Materials and MethodsIslets were obtained by collagenase digestion [7] from the pancreases of male Wistar rats fed on regular rat diet (PRM, Dixon, Ware, Hefts, UK). Hypophysectomised rats were purchased from Charles River Laboratories and used after 4-5weeks from hypophysectomy. Islets were cultured for 4 days as described previously [2]. The culture medium was RPM1 1640 [8] containing glucose (6mmol/1), penicillin (0.1 mg/ml), streptomycin (0.1 mg/ml) and 10% (v/v) inactivated calf serum (Wellcome, Beckenham, Kent, UK) and was supplemented, where stated, with rat growth hormone 1 .ug/ml (National Institutes of Health, Bethesda, USA, lot GH-B-6); the pH was buffered at 7.4 with N-2-hydroxyethylpiperazine-N'-2-ethane sulph...

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“…Growth hormone (GH) has an insulinotropic action in addition to its peripheral diabetogenic effects (4,5). In vitro studies have confirmed a stimulatory effect on fJ-cell replication and insulin production in fetal (6), neonatal (7), and adult (8,9) rat islets. In the fetal rat, the stimulatory effects of GH may largely be mediated via local production of insulin-like growth factor I (IGF-I) (10), as in several other tissues (11).…”

mentioning

confidence: 99%

Effects of Growth Hormone and Insulin-Like Growth Factor I on Endocrine Function of Human Fetal Islet-Like Cell Clusters During Long-Term Tissue Culture

Otonkoski

Knip²,

Wong³

et al. 1988

Diabetes

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The effects of recombinant human growth hormone (GH, 1 micrograms/ml) and insulin-like growth factor I (IGF-I, 200 ng/ml) on the production of insulin and glucagon by human fetal islet-like cell clusters (ICCs) were studied in tissue culture. ICCs were derived after collagenase digestion and culture of pancreases from 16 fetuses (mean gestational age 15.6 wk). The ICCs were cultured with or without GH or IGF-I for 7 or 31 days. Basal rates of insulin and glucagon production were not altered by GH during the first 17 days of culture, but the release of both hormones was increasingly augmented by GH during the last 2 wk of culture (131% increase in insulin and 85% in glucagon compared with controls). ICCs cultured for 7 days in the presence of GH secreted more insulin when incubated for 120 min in 20 mM than in 2 mM glucose (2.1-fold response, P less than .05), whereas ICCs maintained in basal medium did not respond to glucose. GH had no effect on DNA and insulin content or insulin biosynthesis. Exogenous IGF-I caused a 28% suppression of insulin release (P less than .05) between days 4 and 10 of culture but induced a 49% increase in the mean secretion rate during the last week (days 25-31, P less than .01). Glucagon release was not affected by exogenous IGF-I. In contrast to GH, exogenous IGF-I induced a twofold increase in the DNA content of the 7-day--cultured ICCs. However, insulin biosynthesis and release were markedly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Cited by 24 publications

References 28 publications

Influence of protein nutrition on the response of growing lambs to exogenous bovine growth hormone

Influence of protein nutrition on the response of growing lambs to exogenous bovine growth hormone

Effects of hypophysectomy and growth hormone on cultured islets of Langerhans of the rat

Effects of Growth Hormone and Insulin-Like Growth Factor I on Endocrine Function of Human Fetal Islet-Like Cell Clusters During Long-Term Tissue Culture

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