Effects of Growth-Hormone Release-Inhibiting Hormone on Circulating Glucagon, Insulin, and Growth Hormone in Normal, Diabetic, Acromegalic, and Hypopituitary Patients

Mortimer, C. H.; Carr, Denis H.; Lind, T.; Bloom, Stephen R.; Mallinson, C. N.; Schally, Andrew V.; Tunbridge, W. M. G.; Yeomans, Lynne; Coy, David H.; Kastin, Abba J.; Besser, G. M.; Hall, R.

doi:10.1016/s0140-6736(74)92903-1

Cited by 268 publications

(83 citation statements)

References 13 publications

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“…While investigating the effect of somatostatin on GH release, several groups made the unexpected observation that the peptide also inhibited insulin release [1,57,35,39,69,18,32,33,62,29,34]. This was particularly interesting in view of the hypothesis that impaired insulin release is a primary derangement in diabetes mellitus.…”

Section: On Endocrine Functionsmentioning

confidence: 99%

Somatostatin — both hormone and neurotransmitter?

1978

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Section: On Endocrine Functionsmentioning

confidence: 99%

Somatostatin — both hormone and neurotransmitter?

1978

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“…Recently, a new approach to the study of glucagon and growth hormone physiology has been made possible by the discovery of somatostatin. This hypothalamic peptide (20) inhibits the secretion of human glucagon (9,(21)(22)(23), insulin (23)(24)(25)(26), and growth hormone (24, 27,28) but has no intrinsic effect on glucose (22,29,30) or lipid (31,32) metabolism. Infusion of somatostatin lowers plasma glucose, glucagon, and growth hormone levels in normal man (20, 28) and in insulin-dependent diabetics (21).…”

Section: Introductionmentioning

confidence: 99%

“…This hypothalamic peptide (20) inhibits the secretion of human glucagon (9,(21)(22)(23), insulin (23)(24)(25)(26), and growth hormone (24, 27,28) but has no intrinsic effect on glucose (22,29,30) or lipid (31,32) metabolism. Infusion of somatostatin lowers plasma glucose, glucagon, and growth hormone levels in normal man (20, 28) and in insulin-dependent diabetics (21). Since similar decrements in plasma glucose levels also occur in hypophysectomized diabetic and normal subjects who lack growth hormone (21,22), these studies have provided direct evidence that endogenous glucagon participates in normal glucose homeostasis and contributes to diabetic hyperglycemia in man.…”

Section: Introductionmentioning

confidence: 99%

Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin.

Gerich¹,

Lorenzi²,

Bier³

et al. 1976

J. Clin. Invest.

194

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A B S T R A C T To study the individual effects of glucagon and growth hormone on human carbohydrate and lipid metabolism, endogenous secretion of both hormones was simultaneously suppressed with somatostatin and physiologic circulating levels of one or the other hormone were reproduced by exogenous infusion. The interaction of these hormones with insulin was evaluated by performing these studies in juvenile-onset, insulin-deficient diabetic subjects both during infusion of insulin and after its withdrawal.Infusion of glucagon (1 ng/kg min) during suppression of its endogenous secretion with somatostatin produced circulating hormone levels of approximately 200 pg/ml. When glucagon was infused along with insulin, plasma glucose levels rose from 94±8 to 126±+12 mg/100 ml over 1 h (P <0.01); growth hormone, P-hydroxybutyrate, alanine, FFA, and glycerol levels did not change. When insulin was withdrawn, plasma glucose, fi-hydroxybutyrate, FFA, and glycerol all rose to higher levels (P < 0.01) than those observed under similar conditions when somatostatin alone had been infused to suppress glucagon secretion. Thus, under appropriate conditions, physiologic levels of glucagon can stimulate lipolysis and cause hyperketonemia and hyperglycemia in man; insulin antagonizes the lipolytic and ketogenic effects of glucagon more effectively than the hyperglycemic effect. produced circulating hormone levels of approximately 6 ng/ml. When growth hormone was administered along with insulin, no effects were observed. After insulin was withdrawn, plasma P-hydroxybutyrate, glycerol, and FFA all rose to higher levels (P < 0.01) than those observed during infusion of somatostatin alone when growth hormone secretion was suppressed; no difference in plasma glucose, alanine, and glucagon levels was evident. Thus, under appropriate conditions, physiologic levels of growth hormone can augment lipolysis and ketonemia in man, but these actions are ordinarily not apparent in the presence of physiologic levels of insulin. INTRODUCTIONThe physiologic importance of glucagon and growth hormone in human carbohydrate and lipid homeostasis is poorly understood. Administration of pharmacologic amounts of glucagon can augment lipolysis (1-4), ketogenesis (1-4), and glucose production (1-5) in man, but these effects are difficult to interpret because such quantities of glucagon may promote growth hormone (6) and catecholamine (7) release. Moreover, similar results have not been consistently observed in studies using physiologic concentrations of glucagon (3,8,9). Evidence for the participation of growth hormone in human lipid and carbohydrate metabolism is based largely on results obtained after administration of pharmacologic quantities of growth hormone and on observations in hypophysectomized individuals. Growth hormone, when administered in pharmacologic doses, reportedly diminishes glucose utilization (10-15) and promotes lipolysis (10, 16) and ketosis (10, 15, 16) in man, but similar

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“…During the first days of life, glucose stimulates the ['H] leucine incorporation into insulin through proinsulin biosynthesis in isolated islets of rat pancreas (2)(3)(4). Several agents which naturally occur in pancreas such as cAMP (5)(6)(7) and somatostatin (8) have ben postulated to play an important role in the regulation of insulin secretion in neonates (9) and in adults (5)(6)(7)(10)(11)(12)(13)(14)(15)(16)(17)(18). However, there is currently no information available regarding the effect of somatostatin on insulin biosynthesis; moreover, the precise relationship between glucose, cAMP, and somatostatin on the beta cell function remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…Somatostatin is known as a potent inhibitor of glucagon release (61-62) and of both the acute and the chronic phase of insulin secretion (14)(15)(16)(17)(18). Because of its preferential action on glucagon (61)(62), it has been found to be efficient in lowering blood glucose in experimental diabetes (15) and its use in human diabetes has been proposed.…”

mentioning

confidence: 99%

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

García¹,

Jarrousse²,

Rosselin³

1976

J. Clin. Invest.

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A B S T R A C T The purpose of the present study was to investigate the regulation of insulin biosynthesis during the perinatal period. The incorporation of [3H]leucine into total immunoreactive insulin (IRI) and into IRI fractions was measured by a specific immunoprecipitation procedure after incubation, extraction, and gel filtration in isolated 3-day-old rat pancreases without prior isolation of islets. IRI fractions were identified by their elution profile, their immunological properties, and their ability to compete with the binding of "I-insulin in rat liver plasma membranes. No specific incorporation of [3H]leucine was found in the IRI eluted in the void volume, making it unlikely that this fraction behaves as a precursor of (pro)insulin in this system. In all conditions tested, the incorporation of [8H]leucine was linearly correlated with time. Optimal concentration of glucose (11 mM cose and was not modified by any further increase in glucose concentrations up to 27.5 mM. Theophylline or dbcAMP at 10 mM concentration did not reverse the somatostatin inhibitory effect on either insulin biosynthesis or release. Somatostatin also inhibited both processes in isolated islets from the 3-day-old rat pancreas. High Ca"+ concentration in the incubation medium reversed the inhibitory effect of somatostatin on glucoseinduced insulin biosynthesis as well as release. In both systems the inhibitory effect of somatostatin on insulin biosynthesis and release correlated well. Glipizide (10-100 ,M) and tolbutamide (400 ELM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [8H]leucine incorporation into IRI. The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas.These data suggest the following conclusions: (a) the role of the cAMP-phosphodiesterase system on insulin biosynthesis is likely to be greater in newborns than in adults; (b) the greater effectiveness of glucose and the cAMP system on insulin biosynthesis than on insulin release might possibly be related to the rapid accumulation of pancreatic IRI which is observed in the perinatal period; (c) somatostatin, by direct interaction with the endocrine tissue, can inhibit glucose and cAMPinduced insulin biosynthesis as well as release; calcium reverses this inhibition; (d) sulfonylureas inhibit insulin biosynthesis in newborn rat pancreas an effect which has

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Effects of Growth-Hormone Release-Inhibiting Hormone on Circulating Glucagon, Insulin, and Growth Hormone in Normal, Diabetic, Acromegalic, and Hypopituitary Patients

Cited by 268 publications

References 13 publications

Somatostatin — both hormone and neurotransmitter?

Somatostatin — both hormone and neurotransmitter?

Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin.

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

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