Metabolic response to human growth hormone during prolonged starvation

Felig, Philip; Marliss, Errol B.; Cahill, George F.

doi:10.1172/jci106508

Cited by 83 publications

(29 citation statements)

References 24 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, previous investigators have also noted that continuous infusions of ketone acids fail to increase plasma insulin in peripheral blood (18,28,29). Although growth hormone was not measured in the present study, other reports have shown that increased levels of growth hormone are without effect on total urinary nitrogen excretion in prolonged starvation (30).…”

Section: Discussioncontrasting

confidence: 61%

Effect of ketone infusions on amino acid and nitrogen metabolism in man.

Sherwin¹,

Hendler²,

Felig³

1975

J. Clin. Invest.

328

123

View full text Add to dashboard Cite

A B S T R A C T To evaluate the role of hyperketonemia in the hypoalaninemia and decreased protein catabolism of prolonged starvation, Na DL-P-hydroxybutyrate was administered as a primed continuous 3-6-h infusion in nonobese subjects and in obese subjects in the postabsorptive state and after 3 days and 3-51 wk of starvation. An additional obese group received 12-h ketone infusions on 2 consecutive days after 5-10 wk of fasting.The ketone infusion in nonobese and obese subjects studied in the postabsorptive state resulted in total blood ketone acid levels of 1.1-1.2 mM, a 5-15 mg/100 ml decrease in plasma glucose, and unchanged levels of insulin, glucagon, lactate, and pyruvate. Plasma alanine fell by 21% (P <0.001) in 3 h. In contrast, other amino acids were stable or varied by less than 10%. Infusions lasting 6 h reduced plasma alanine by 37%, reaching levels comparable to those observed in prolonged starvation. Equimolar infusions of NaCl and/or administration of NaHCOs failed to alter plasma alanine levels.During prolonged fasting, plasma alanine, which had fallen by 40% below prefast levels, fell an additional 30% in response to the ketone infusion. In association with repeated prolonged (12 h) infusions in subjects fasted 5-10 wk, urinary nitrogen excretion fell by 30%, returning to base line after cessation of the infusions and paralleling the changes in plasma alanine. Ketone infusions resulted in two-to fourfold greater increments in blood ketone acids in fasted as compared to postabsorptive subjects.It is concluded that increased blood ketone acid levels induced by infusions of Na DL-P-hydroxybutyrate result in hypoalaninemia and in nitrogen conservation in starvation. These data suggest that hyperketonemia may be a contributory factor in the decreased availability of circulating alanine and reduction in protein catabolism characteristic of prolonged fasting. INTRODUCTIONIn fasting man survival is dependent upon the conservation of body protein stores as well as the continuous supply of energy-yielding fuels for brain metabolism (1). The need for gluconeogenesis and concomitantly the rate of protein breakdown progressively decline in prolonged starvation as ketone acids replace glucose as the major fuel consumed by the brain (2). The diminution in hepatic gluconeogenesis in prolonged fasting is mediated by a reduction in circulating glucogenic amino acids, particularly alanine, and a decrease in the outflow of these amino acids from muscle (3, 4). After a prolonged fast, plasma alanine decreases to a greater extent than that of all other amino acids, while splanchnic uptake and peripheral release of alanine are reduced to less than 50% of postabsorptive levels (3, 4).

show abstract

Section: Discussioncontrasting

confidence: 61%

Effect of ketone infusions on amino acid and nitrogen metabolism in man.

Sherwin¹,

Hendler²,

Felig³

1975

J. Clin. Invest.

328

123

View full text Add to dashboard Cite

show abstract

“…Infusion of growth hormone along with somatostatin in the present studies had no effect on plasma glucose and alanine levels but did result in significantly (P <0.01) greater rises in plasma FFA, glycerol, and 8i-hydroxybutyrate levels than were observed with somatostatin alone; these rises approximated those found during control experiments after withdrawal of insulin. Previous studies using pharmacologic doses of exogenous growth hormone have demonstrated that growth hormone can augment lipolysis and cause hyperketonemia in man (10,12,13,15,16), but to our knowledge the present studies represent the first demonstration that these effects occur with physiologic levels of growth hormone.…”

Section: Discussionmentioning

confidence: 47%

“…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)(11)(12)(13)(14)(15) and promotes lipolysis (10,16) and ketosis (10, 15,16) (10), these metabolic effects may not reflect growth hormone deprivation alone (17) because mobilization of FFA and ketosis can occur in growth hormonedeficientman (18,19). Recently, a new approach to the study of glucagon and growth hormone physiology has been made possible by the discovery of somatostatin.…”

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

View full text Add to dashboard Cite

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

show abstract

“…1 4.65 mmol/liter at the 24-h interval, and then progressively depressed the levels to a minimal concentration of 3.30 mmol/liter on day 42, the fourth postinfusion day. Plasma free amino acids during fasting were measured in subject C. R. before and during the hydrocortisone infusion periods (Table III) tration is shown in Fig.…”

Section: Resultsmentioning

confidence: 95%

“…Previous studies have shown that this steady state provides an ideal condition for investigating the acute metabolic effects of exogenously administered hormones (3)(4)(5). We Received for publication 1 August 1972 and in revised form 21 May 1973. and hormones as well as on the urinary excretion of nitrogenous compounds and ketone bodies.…”

Section: Introductionmentioning

confidence: 99%