THE EFFECTS OF GROWTH HORMONE AND KETONE BODIES ON CARBOHYDRATE METABOLISM IN DIAPHRAGM FROM NORMAL AND HYPOPHYSECTOMIZED RATS

1961 ◽  
Vol 21 (4) ◽  
pp. 443-451 ◽  
Author(s):  
J. H. OTTAWAY
Keyword(s):  
Growth Hormone ◽  
Glucose Uptake ◽  
Carbohydrate Metabolism ◽  
Ketone Bodies ◽  
Glycogen Synthesis ◽  
Significant Stimulation ◽  
Lactate Output ◽  
Hypophysectomized Rats ◽  
Lactate Formation ◽  
Normal Diaphragm

SUMMARY The disposition of carbohydrate in isolated diaphragm from normal and hypophysectomized rats has been studied, after addition of acetate, acetoacetate or β-hydroxybutyrate ± ox growth hormone (GH) to the incubation medium in which glucose was always present. 1. In normal diaphragm acetoacetate alone depressed glucose uptake by about 20%, without inhibiting glycogen synthesis. There was a considerable inhibition of pyruvate formation. This effect was not seen in diaphragm from hypophysectomized rats. 2. Acetate alone inhibited glycogen synthesis in diaphragm from normal, but not hypophysectomized, rats. 3. β-Hydroxybutyrate alone inhibited pyruvate formation in diaphragm from hypophysectomized, but not normal, rats. 4. With normal diaphragm the addition of GH to the medium (1 μg/ml.) produced only slight changes in carbohydrate metabolism, although there was a significant stimulation of glucose uptake when acetate was present. With diaphragm from hypophysectomized animals GH at this concentration caused a striking increase in glucose uptake, accompanied by increased glycogen synthesis (insulin-like effect). In the absence of substrate other than glucose GH increased lactate output; in the presence of acetate, GH inhibited lactate formation. 5. Hypophysectomy did not affect the rate of uptake of acetoacetate, but the uptake of acetate was markedly increased. 6. In confirmation of previous work GH did not affect the uptake of acetoacetate by diaphragm from either normal or hypophysectomized rats.

PURIFICATION AND PROPERTIES OF A HYPOGLYCAEMIC PEPTIDE FROM OX GROWTH HORMONE

1961 ◽  
Vol 23 (2) ◽  
pp. 193-207 ◽  
Author(s):  
A. K. HUGGINS ◽  
J. H. OTTAWAY
Keyword(s):  
Growth Hormone ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Rat Diaphragm ◽  
Low Concentrations ◽  
Purification And Properties ◽  
Lactate Output ◽  
Normal Rat ◽  
High Concentrations ◽  
Very High

SUMMARY A peptide has been isolated from crystalline ox growth hormone (GH) which stimulates glucose uptake by isolated rat diaphragm when incubated with it at low concentrations (0·01 μg./ml. medium). The peptide also causes a slight but persistent hypoglycaemia in fasted mice and rabbits. The increase in glucose uptake by diaphragm is not accompanied by increased glycogen synthesis; in certain circumstances it causes a diminution in lactate output. When incubated with normal rat diaphragm in the absence of acetate, very high concentrations (10 μg./ml.) cause an inhibition of glucose uptake. The peptide appears to have negligible effects on fat metabolism. The peptide has a mol. wt. of 5,000–10,000, an isoelectric point of about pH 6, and an N-terminal methionine. The amino acid composition is noteworthy for the complete absence of basic amino acids. It is concluded that ox GH freed from this peptide will stimulate glycogen synthesis by muscle without increasing the uptake of glucose.

Mechanism of growth hormone-induced postprandial carbohydrate intolerance in humans

1991 ◽  
Vol 260 (4) ◽  
pp. E513-E520 ◽  
Author(s):  
P. Butler ◽  
E. Kryshak ◽  
R. Rizza
Keyword(s):  
Carbon Dioxide ◽  
Growth Hormone ◽  
Glucose Uptake ◽  
Ketone Bodies ◽  
Plasma Concentrations ◽  
Substrate Uptake ◽  
Glucose Release ◽  
Hepatic Glucose ◽  
Hepatic Glucose Release ◽  
Carbohydrate Intolerance

Growth hormone excess can cause postprandial carbohydrate intolerance. To determine the contribution of splanchnic and extrasplanchnic tissues to this process, subjects were fed an isotopically labeled mixed meal after either a 12-h infusion of saline or growth hormone (4 micrograms.kg-1.h-1 [corrected]). Growth hormone infusion resulted in higher glucose and insulin concentrations both before and after meal ingestion. Despite growth hormone-induced hyperglycemia and hyperinsulinemia, postprandial hepatic glucose release and carbon dioxide incorporation into glucose (a qualitative estimate of gluconeogenesis) were similar to those present during saline, suggesting altered hepatic regulation. This was confirmed when glucose was infused in the absence of growth hormone to achieve glucose (and insulin) concentrations comparable to those present during growth hormone infusion. Although growth hormone excess did not alter splanchnic uptake of ingested glucose, it resulted in a fivefold increase in postprandial hepatic glucose release (578 +/- 31 vs. 117 +/- 10 mg.kg-16 h-1, P less than 0.01), less suppression of carbon dioxide incorporation into glucose (-13 +/- 9 vs. -53 +/- 12 mg.kg-1. 6-h-1, P less than 0.01), and lower glucose uptake (1,130 +/- 59 vs. 1,850 +/- 150 mg.kg-1.6 h-1, P less than 0.01). The decrease in postprandial glucose uptake did not appear to be mediated by a change in substrate uptake since postprandial plasma concentrations and forearm balance of lactate, free fatty acids, and ketone bodies did not differ in the presence and absence of growth hormone excess.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum factor in fasted rats inhibiting carbohydrate metabolism in the isolated diaphragm

1960 ◽  
Vol 198 (5) ◽  
pp. 1075-1078 ◽  
Author(s):  
E. R. Berman ◽  
E. Wertheimer
Keyword(s):  
Glucose Uptake ◽  
Carbohydrate Metabolism ◽  
Glycogen Synthesis ◽  
Rat Diaphragm ◽  
Serum Factor ◽  
Inhibitory Factors ◽  
Fasted Rats ◽  
Isolated Rat

A factor has been found in the serum of fasted rats which inhibits glucose uptake and glycogen synthesis in the isolated rat diaphragm. It does not affect CO2 production or O2 uptake. It is nondialyzable, stable in the cold and also stable when heated to 58°C for 1 hour. It was found in Cohn fraction IV-V. Its action did not resemble any of the known hormones, nor could it be identified as one of the inhibitory factors found in diabetic serum.

THE EFFECT OF GROWTH HORMONE AND OF CORTISOL ON THE RESPONSE OF ISOLATED RAT DIAPHRAGM TO THE STIMULATING EFFECT OF INSULIN ON GLUCOSE UPTAKE AND ON INCORPORATION OF AMINO ACIDS INTO PROTEIN

1959 ◽  
Vol 18 (4) ◽  
pp. 395-408 ◽  
Author(s):  
K. L. MANCHESTER ◽  
P. J. RANDLE ◽  
F. G. YOUNG
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Glucose Uptake ◽  
Carbohydrate Metabolism ◽  
Rat Diaphragm ◽  
Pituitary Growth Hormone ◽  
Isolated Rat ◽  
Stimulation Of

SUMMARY 1. The effect of hypophysectomy, or of adrenalectomy, and injection of pituitary growth hormone (GH) or of cortisol, on the uptake of glucose and the incorporation of glycine into protein by isolated rat diaphragm, and the effect of the addition of insulin in vitro on these processes, has been studied. 2. Both hypophysectomy and adrenalectomy raised the uptake of glucose by isolated diaphragm, while treatment of the intact or of the hypophysectomized rat with GH, or of the intact or of the adrenalectomized rat with cortisol, depressed it. Although hypophysectomy and adrenalectomy did not influence the additional glucose uptake induced by 200 mu./ml. of insulin in vitro, both these operations enhanced the effect of 0·1–1·0 mu./ml. of insulin on glucose uptake by diaphragm in vitro. Treatment of the rat with GH or cortisol diminished the rise in glucose uptake of diaphragm induced by 0·1–1·0 mu./ml. insulin. 3. Hypophysectomy depressed, and administration of GH to the intact or hypophysectomized rat raised, the incorporation of glycine into protein of the isolated diaphragm, but neither of these operations altered the magnitude of the stimulation of incorporation induced by 1·0 mu./ml. insulin. 4. Adrenalectomy raised, and administration of cortisol to the intact or adrenalectomized rat depressed, the incorporation of glycine into protein of the isolated diaphragm; adrenalectomy enhanced, the injection of cortisol diminished, the effect of 1·0 mu./ml. insulin on these processes. 5. The possibility that GH directs insulin towards the stimulation of protein synthesis, in part by restraining the action of insulin on carbohydrate metabolism, is discussed.

Disorders of carbohydrate metabolism

2011 ◽  
pp. 1677-1683
Author(s):  
Robin H. Lachmann
Keyword(s):  
Fatty Acid ◽  
Carbohydrate Metabolism ◽  
Fatty Acid Oxidation ◽  
Ketone Bodies ◽  
Glycogen Synthesis ◽  
Acid Oxidation ◽  
Defence Mechanisms ◽  
Glucose Homoeostasis ◽  
Alternative Sources ◽  
Glycogen Stores

Many disorders of carbohydrate metabolism are characterized by hypoglycaemia and attacks of neuroglycopenia. Hypoglycaemia can also be caused by disorders affecting the use of other fuels, such as those producing fatty acids and ketone bodies which are important alternative sources of energy. Thus when investigating a patient with hypoglycaemia it is necessary to investigate not only pathways that provide glucose directly, but also those which spare glucose utilization and thus provide defence mechanisms when carbohydrate energy sources become depleted. The defence mechanisms that are activated during fasting to preserve blood glucose are: ◆ glycogenolysis—glucose liberation from glycogen degradation ◆ gluconeogenesis—glucose production from pyruvate/lactate and from noncarbohydrate sources such as glucogenic amino acids and glycerol ◆ fatty acid β‎-oxidation—catabolism of triglycerides to acetyl-CoA and ketone bodies The interrelation between these glucose generating pathways is shown in Fig. 12.3.1.1. Although there is much overlap, the activation of these defence mechanisms during fasting is sequential. The first defence mechanism, glycogenolysis, is exhausted within 8–12 h of fasting. The second and third defence mechanisms provide glucose once glycogen stores have been depleted. In a patient with glycogen storage disease (GSD) where glycogenolysis is blocked, gluconeogenesis and fatty acid oxidation are activated immediately on fasting and can only maintain normoglycaemia for a few hours. In patients with defects affecting gluconeogenesis or fatty acid oxidation, hypoglycaemia does not occur until glycogen stores have been depleted. When more than one pathway is affected, as in GSD I, where neither glycogenolysis nor gluconeogenesis can release glucose into the circulation, patients can be entirely dependent on oral carbohydrate intake to maintain normoglycaemia. These pathways are also susceptible to hormonal influences. Insulin in particular inhibits all three pathways and stimulates some enzymes of the reverse pathways: glycogen synthesis, glycolysis, and fatty acid synthesis. Therefore hyperinsulinaemia of whatever cause leads to severe hypoglycaemia which is resistant to treatment. Other hormones, such as glucagon, adrenaline, and growth hormone, also activate some enzymes of glucose homoeostasis, though less markedly. This is discussed elsewhere. The metabolism of the other monosaccharides, galactose and fructose, is connected with that of glucose. As well as causing hypoglycaemia, inherited defects that affect the metabolism of these sugars lead to the accumulation of toxic metabolites which also contribute to pathology (see below).

Acute effect of growth hormone to induce peripheral insulin resistance is independent of FFA and insulin levels in rats

1999 ◽  
Vol 277 (4) ◽  
pp. E742-E749 ◽  
Author(s):  
Jason K. Kim ◽  
Cheol S. Choi ◽  
Jang H. Youn
Keyword(s):  
Insulin Resistance ◽  
Growth Hormone ◽  
Glucose Uptake ◽  
Plasma Insulin ◽  
Glycogen Synthesis ◽  
Plasma Free Fatty Acid ◽  
Acute Effect ◽  
Insulin Levels ◽  
Peripheral Insulin Resistance ◽  
Plasma Ffa

To examine whether growth hormone (GH) induces peripheral insulin resistance by altering plasma free fatty acid (FFA) or insulin levels, the effects of GH infusion on insulin-stimulated glucose fluxes were studied in conscious rats under two protocols. In study 1, either saline ( n = 7) or human recombinant GH (21 μg ⋅ kg−1 ⋅ h−1; n = 8) was infused for 300 min, and insulin-stimulated glucose fluxes were estimated during the final 150-min period of hyperinsulinemic euglycemic clamps. In study 2, hyperinsulinemic euglycemic clamps were first conducted for 150 min (to raise plasma insulin and suppress FFA levels), and saline or GH ( n = 7 for each) was subsequently infused for the following 300-min clamp period. In study 1, GH infusion in the basal state did not significantly alter plasma FFA or insulin levels. In contrast, GH infusion decreased insulin-stimulated glucose uptake, glycolysis, and glycogen synthesis by 32, 27, and 40%, respectively ( P < 0.05). In study 2, GH infusion during hyperinsulinemic euglycemic clamps did not alter plasma FFA or insulin levels ( P > 0.05). GH infusion had no effect on insulin-stimulated glucose uptake during the initial 150 min but eventually decreased insulin-stimulated glucose uptake by 37% ( P < 0.05), similar to the results in study 1. These data indicate that GH induces peripheral insulin resistance independent of plasma FFA and insulin levels. The induction of insulin resistance was preceded by suppression of glycogen synthesis, consistent with the hypothesis that metabolic impairment precedes and causes development of peripheral insulin resistance.

scholarly journals Acute effects of phorbol esters on the protein-synthetic rate and carbohydrate metabolism of normal and mdx mouse muscles

1991 ◽  
Vol 275 (2) ◽  
pp. 477-483 ◽  
Author(s):  
P A MacLennan ◽  
A McArdle ◽  
R H Edwards
Keyword(s):  
Glucose Uptake ◽  
Carbohydrate Metabolism ◽  
Phorbol Esters ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Kinetic Studies ◽  
Mdx Mouse ◽  
Mdx Mice

1. mdx mice do not express dystrophin, the product of the gene which is defective in Duchenne and Becker muscular dystrophy. We have previously shown that protein-synthetic rates (ks) are increased in mdx mouse muscles [MacLennan & Edwards (1990) Biochem. J. 268, 795-797]. 2. The tumour-promoting stereoisomer of phorbol 12,13-didecanoate (4 beta-PDD) acutely increased the ks of muscles from mdx and wild-type (C57BL/10) mice incubated in vitro in the absence of insulin. The effects of 4 beta-PDD are presumably mediated by activation of protein kinase C (PKC). 3. The muscle glycogen concentrations of mdx mice were higher than those of C57BL/10 mice. Studies performed in vivo and in vitro suggested that the effect might be at least partially due to increased rate of glycogen synthesis in mdx muscle. 4. 4 beta-PDD increased the glycogen-synthetic rates rates of C57BL/10, but not mdx, muscles incubated in vitro in the absence of insulin. 5. In muscles from both species incubated in the absence of insulin, treatment with 4 beta-PDD also induced increased rates of glucose uptake and lactate production. Kinetic studies of C57BL/10 and mdx muscles suggested that 4 beta-PDD raised the Vmax. of glucose uptake, but did not alter the Km for the process. 6. The possible role of PKC in controlling the protein and carbohydrate metabolism of normal and mdx mouse muscles is discussed.

scholarly journals Regulation of fatty acid and carbohydrate metabolism by insulin, growth hormone and tri-iodothyronine in hepatocyte cultures from normal and hypophysectomized rats

1989 ◽  
Vol 258 (2) ◽  
pp. 547-552 ◽  
Author(s):  
S Betley ◽  
K G M M Alberti ◽  
L Agius
Keyword(s):  
Growth Hormone ◽  
Fatty Acid ◽  
Carbohydrate Metabolism ◽  
Primary Cultures ◽  
Fold Increase ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Hypophysectomized Rats ◽  
In Cells

The interactions of insulin, growth hormone (somatotropin) and tri-iodothyronine (T3) in the long-term (24 h) regulation of fatty acid and carbohydrate metabolism were studied in hepatocyte primary cultures isolated from normal or hypophysectomized Sprague-Dawley rats. Hepatocytes from hypophysectomized rats had similar rates of palmitate metabolism, but lower rates of ketogenesis, than hepatocytes from normal rats. They also had a lower endogenous triacylglycerol content and lower activities of NADP-linked dehydrogenases than did cells from normal rats. The inhibitions of ketogenesis and gluconeogenesis by insulin were more marked in hepatocytes from hypophysectomized than from normal rats. Insulin caused a 7-10-fold increase in cellular glycogen in hepatocytes from hypophysectomized rats, compared with a 2-3-fold increase in cells from normal rats, and it increased cellular triacylglycerol by 65% in cells from hypophysectomized rats, compared with 11% in cells from normal rats. In hepatocytes from hypophysectomized rats, growth hormone and T3 increased ketogenesis both separately and in combination (12% and 23% respectively; P less than 0.05), whereas in hepatocytes from normal rats only the combination of growth hormone and T3 caused a significant increase in ketogenesis. In cells from hypophysectomized rats, T3 and growth hormone had different effects on carbohydrate metabolism: T3, but not growth hormone, potentiated the anti-gluconeogenic and glycogenic effects of insulin. It is concluded that hypophysectomy increases the responsiveness of hepatocytes to insulin, growth hormone and T3, and that growth hormone and T3 regulate fatty acid and carbohydrate metabolism by different mechanisms.

GROWTH HORMONE AND RADIO-SULFATE INCORPORATION IN COSTAL CARTILAGE

1961 ◽  
Vol 37 (2) ◽  
pp. 176-182 ◽  
Author(s):  
Elliott J. Collins ◽  
Vernon F. Baker
Keyword(s):  
Growth Hormone ◽  
Costal Cartilage ◽  
Time Response ◽  
Hormone Activity ◽  
Reliable Estimation ◽  
Hypophysectomized Rats ◽  
Related Response ◽  
Sulfate Incorporation

ABSTRACT The characteristics and nature of the effect of growth hormone on the incorporation of radio-sulfate into the costal cartilage of hypophysectomized rats has been studied. The time-response studies indicate that a reliable estimation of growth hormone activity can be ascertained within a 24 hour period, and a reproducible dose-related response can be obtained at dosage levels ranging from 12-48 μg. Growth hormone stimulates the synthesis of organic sulfates and accumulation of inorganic sulfates within 48 hours.

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