Effect of growth hormone on hepatic glucose and insulin metabolism after oral glucose in conscious dogs

1994 ◽  
Vol 267 (3) ◽  
pp. E454-E460
Author(s):  
Y. Okuda ◽  
J. Pena ◽  
J. Chou ◽  
J. B. Field
Keyword(s):  
Growth Hormone ◽  
Portal Vein ◽  
Hepatic Uptake ◽  
Oral Glucose ◽  
Gh Treatment ◽  
Insulin Metabolism ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Before And After

This study examined the effect of growth hormone (GH) on hepatic glucose metabolism and on the fractional extraction of insulin and glucagon after oral glucose administration. GH treatment [canine GH (0.75 mg/day for 7 days)] significantly increased basal portal vein and hepatic artery flow (P < 0.01 compared with pre-GH treatment). After GH treatment and after oral glucose, glucose levels significantly exceeded those before GH at 100 and 120 min in arterial and portal vein plasma and 120 min in the hepatic vein. The net hepatic uptake of glucose was similar before and after GH treatment. The increment of net nonhepatic splanchnic insulin balance above basal was 131 +/- 31 mU.kg-1.3 h-1 before and 272 +/- 46 mU.kg-1.3 h-1 after GH treatment (P < 0.05). An increase in fractional hepatic extraction of insulin occurred before GH treatment and was significantly greater at 60 min. In summary, despite the increased insulin content after GH administration, there was no change in hepatic uptake of glucose, indicating that the liver was also the site of insulin resistance.

THE EFFECT OF THE PROGESTOGEN ETHYNODIOL DIACETATE ON GLUCOSE, INSULIN, AND GROWTH HORMONE AFTER SIX MONTHS TREATMENT

1972 ◽  
Vol 70 (2) ◽  
pp. 373-384 ◽  
Author(s):  
W. N. Spellacy ◽  
W. C. Buhi ◽  
S. A. Birk
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Oral Glucose ◽  
Hormone Levels ◽  
Glucose Levels ◽  
Ethynodiol Diacetate ◽  
Tolerance Curve

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.

Counterregulation of insulin-induced hypoglycaemia in primary hypothyroidism

1986 ◽  
Vol 111 (4) ◽  
pp. 516-521
Author(s):  
Nina Clausen ◽  
Per-Eric Lins ◽  
Ulf Adamson ◽  
Bertil Hamberger ◽  
Suad Efendić
Keyword(s):  
Growth Hormone ◽  
Insulin Infusion ◽  
Primary Hypothyroidism ◽  
Constant Rate Infusion ◽  
Counterregulatory Hormones ◽  
Insulin Metabolism ◽  
Hormonal Responses ◽  
Glucose Levels ◽  
Constant Rate ◽  
Rate Infusion

Abstract. Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counterregulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32–52 years, TSH-values 66–200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin, C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h. During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.

Pathway and carbon sources for hepatic glycogen repletion in dogs

1991 ◽  
Vol 260 (2) ◽  
pp. E194-E202 ◽  
Author(s):  
A. Mitrakou ◽  
R. Jones ◽  
Y. Okuda ◽  
J. Pena ◽  
N. Nurjhan ◽  
...  
Keyword(s):  
Carbon Sources ◽  
Hepatic Uptake ◽  
Hepatic Glycogen ◽  
Oral Glucose ◽  
Indirect Pathway ◽  
Hepatic Glucose ◽  
Glycogen Repletion ◽  
Hepatic Glucose Uptake ◽  
Labeling Pattern

The present studies were undertaken to quantitate the relative contributions of the indirect and direct pathways for hepatic glycogen repletion and to determine the role of splanchnic tissues in provision of C precursors used for the indirect pathway. For this purpose, we administered oral glucose (1.4 g/kg) enriched with [1-14C]glucose to 18-h fasted dogs and measured net hepatic and net gastrointestinal glucose, lactate, and alanine balance, hepatic and gastrointestinal fractional extraction [( 3H]lactate), release and uptake of lactate, as well as the total amount of hepatic glycogen formed from the oral glucose and the 14C labeling pattern of the glycogen-glucose C. Although net hepatic glucose uptake (8.7 +/- 0.6 g, 27% of the oral load) exceeded the amount of glycogen formed from the oral glucose (6.3 +/- 1.1 g), analysis of radioactivity in C-1 of the glycogen glucose indicated that nearly 50% of the glycogen was formed by the indirect pathway. Net hepatic uptake of lactate (1.4 +/- 0.1 g) and alanine (1.5 +/- 0.1 g) could account for greater than 90% of glycogen formed by the indirect pathway if all of the lactate and alanine taken up by the liver had been incorporated into glycogen. Release of lactate and alanine by splanchnic tissues approximated the amount of lactate and alanine taken up by the liver. However, in addition to taking up lactate, the liver also produced nearly as much lactate as the gastrointestinal tract (1.8 +/- 0.2 vs. 2.0 +/- 0.3 g, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

SERIAL ASSAYS OF PLASMA GROWTH HORMONE IN TREATED AND UNTREATED ACROMEGALY

1974 ◽  
Vol 63 (1) ◽  
pp. 21-34 ◽  
Author(s):  
W. M. HUNTER ◽  
F. J. GILLINGHAM ◽  
P. HARRIS ◽  
J. A. KANIS ◽  
F. M. McGURK ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Test Procedure ◽  
Human Growth ◽  
Tolerance Test ◽  
External Irradiation ◽  
Oral Glucose ◽  
Surgical Removal ◽  
Slow Decline ◽  
Before And After ◽  
Partial Suppression

SUMMARY Assays for human growth hormone (HGH) were carried out on 89 acromegalic patients, 81 of whom were studied before any treatment had been given. Serial studies were undertaken, generally at 6-monthly intervals, with the same test procedure, using a 50 g oral glucose tolerance test (GTT) and identical assay conditions over a period of 8 years. Twenty-three patients were assessed at intervals during periods of up to 4 years whilst they remained untreated. The general picture was one of unchanging HGH levels. Ten patients were studied before and after external irradiation. HGH levels showed a slow continuing fall for as long as 4 years and thereafter they stabilized at one-third of pretreatment values. HGH levels in 12 patients treated with radioactive implants showed an immediate fall to one-third, and thereafter a further slow decline to one-tenth of pretreatment levels. The response in eight patients treated by surgical removal of pituitary tissue and subsequent radiotherapy varied considerably. No patient, treated or untreated, showed evidence of partial suppression of HGH secretion during the GTT although three patients consistently responded to glucose with paradoxical hypersecretion.

scholarly journals Circulating levels of incretin hormones and amylin in the fasting state and after oral glucose in GH-deficient patients before and after GH replacement: a placebo-controlled study

2000 ◽  
pp. 593-599 ◽  
Author(s):  
JO Jorgensen ◽  
AM Rosenfalck ◽  
S Fisker ◽  
B Nyholm ◽  
MS Fineman ◽  
...  
Keyword(s):  
Placebo Group ◽  
Pancreatic Beta Cells ◽  
Plasma Concentrations ◽  
Controlled Study ◽  
Oral Glucose ◽  
Fasting State ◽  
Gh Treatment ◽  
Double Blind ◽  
Gh Replacement ◽  
Before And After

OBJECTIVE: Hyperinsulinemia in association with GH excess is considered a compensatory response to insulin resistance, but the possibility of alternative insulinotropic mechanisms has not been investigated in vivo. It is also unknown how GH influences the secretion from pancreatic beta-cells of amylin, a peptide which regulates prandial glucose homeostasis and may be linked to development of beta-cell dysfunction. We therefore measured plasma concentrations of two gut insulinotropic hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin-releasing peptide (GIP), and total as well as non-glycosylated amylin, in 24 GH-deficient adults before and after 4 months of GH replacement (daily evening injections of 2 IU GH/m). DESIGN: Double-blind, placebo-controlled, parallel study. METHODS: All participants underwent an oral glucose tolerance test (OGTT) at 0 and 4 months. RESULTS: A 33% suppression of fasting GLP-1 concentrations was measured in the GH group at 4 months (P=0.02), whereas a non-significant increase occurred in the placebo group (P=0.08). Fasting levels of GIP and amylin did not change significantly after 4 months in either group. The incremental response in GLP-1 during the OGTT was significantly lower after GH treatment as compared with both baseline (P=0.02) and the response in the placebo group (P=0. 03). The stimulation of GIP secretion following OGTT was similar on all occasions. The OGTT-induced incremental response in non-glycosylated amylin was moderately elevated after GH treatment as compared with placebo (P=0.05). Plasma concentrations of glucose and insulin, both in the fasting state and after the OGTT, were higher after GH treatment, but the ratio between amylin and insulin remained unchanged. CONCLUSIONS: GH-induced hyperinsulinemia is accompanied by proportionate elevations in amylin concentrations and a blunting of gut GLP-1 secretion. The mechanisms underlying the suppression of GLP-1 remain to be elucidated.

Garcinol promotes hepatic gluconeogenesis by inhibiting P300/CBP-associated factor in late-pregnant sows

2020 ◽  
pp. 1-8
Author(s):  
Weilei Yao ◽  
Jun Xia ◽  
Tongxin Wang ◽  
Juan Li ◽  
Lu Huang ◽  
...  
Keyword(s):  
Basal Diet ◽  
Isolated Hepatocytes ◽  
Enzyme Expression ◽  
Glucose Levels ◽  
Hepatic Glucose Metabolism ◽  
Forkhead Box ◽  
Hepatic Glucose ◽  
Diet Control ◽  
Gluconeogenic Enzyme ◽  
Interfering Rna

Abstract Disorder of hepatic glucose metabolism is the characteristic of late-pregnant sows. The purpose of our study was to look into the mechanism of garcinol on the improvement of hepatic gluconeogenic enzyme in late-pregnant sows. Thirty second- and third-parity sows (Duroc × Yorkshire × Landrace, n 10/diet) were fed a basal diet (control) or that diet supplemented with 100 mg/kg (Low Gar) or 500 mg/kg (High Gar) garcinol from day 90 of gestation to the end of farrowing. The livers were processed to measure enzymatic activity. Hepatocytes from pregnant sows were transfected with P300/CBP-associating factor (PCAF) small interfering RNA (siRNA) or treated with garcinol. Dietary garcinol had no effect on average daily feed intake, body weight (BW), backfat and BW gain of late-pregnant sows. Garcinol promoted plasma glucose levels in pregnant sows and newborn piglets. Garcinol up-regulated hepatic gluconeogenic enzyme expression and decreased PCAF activity. Garcinol had no effect on the expression of PPAR-γ co-activator 1α (PGC-1α) and Forkhead box O1 (FOXO1) but significantly increased their activity and decreased their acetylation in late-pregnant sows. Transfection of PCAF siRNA to hepatocytes of pregnant sows increased PGC-1α and FOXO1 activities. Furthermore, in hepatocytes of pregnant sows, garcinol treatment also up-regulated the activities of PGC-1α and FOXO1 and inhibited the acetylation of PGC-1α and FOXO1. Garcinol improves hepatic gluconeogenic enzyme expression in late-pregnant sows, and this may be due to the mechanism of down-regulating the acetylation of PGC-1α and FOXO1 induced by PCAF in isolated hepatocytes.

Alleviation of Non-Islet Cell Tumour Hypoglycaemia by Growth Hormone Therapy is Associated with Changes in IGF Binding Protein-3

1992 ◽  
Vol 29 (3) ◽  
pp. 314-323 ◽  
Author(s):  
J D Teale ◽  
W F Blum ◽  
V Marks
Keyword(s):  
Growth Hormone ◽  
Islet Cell ◽  
Plasma Insulin ◽  
Specific Binding ◽  
Binding Protein ◽  
Insulin Response ◽  
Oral Glucose ◽  
Gh Treatment ◽  
Absolute Increase ◽  
Igfbp 3

The hypoglycaemia caused by non-islet cell tumours is often associated with an increase in plasma insulin-like activity. In many cases there is a relative if not always absolute increase in plasma insulin-like growth factor II (IGF-II). Growth hormone (GH) secretion is almost invariably depressed as is the plasma insulin response to oral glucose. Despite the high concentration of IGFs (i.e. IGF-I and IGF-II) normally found in the plasma of healthy people their potential hypoglycaemic effect is not manifest due to the tightness with which they are bound to specific binding proteins (IGFBPs). Plasma levels of the major binding protein (IGFBP-3), which is GH-dependent, were depressed in three patients with tumour induced hypoglycaemia. Treatment with biosynthetic GH restored IGFBP-3 to levels which were approximately equimolar to total plasma IGF concentrations, alleviated the hypoglycaemia and restored the plasma insulin responses to oral glucose. We suggest that after GH treatment IGF-II is sequestered by stimulated IGFBP-3 in association with a pre-existing acid-labile subunit to form high molecular weight complexes which prevent IGF-II gaining access to tissues receptors through which it exerts its hypoglycaemic effects.

Dose-related effects of epinephrine on glucose production in conscious dogs

1991 ◽  
Vol 260 (3) ◽  
pp. E363-E370 ◽  
Author(s):  
R. W. Stevenson ◽  
K. E. Steiner ◽  
C. C. Connolly ◽  
H. Fuchs ◽  
K. G. Alberti ◽  
...  
Keyword(s):  
Glucose Production ◽  
Hepatic Uptake ◽  
Epinephrine Infusion ◽  
Glucose Levels ◽  
Hepatic Glucose ◽  
Lactate Uptake ◽  
Lactate Levels ◽  
Glucose Output ◽  
Dose Dependent

The effects of increases in plasma epinephrine from 78 +/- 32 to 447 +/- 75, 1,812 +/- 97, or 2,495 +/- 427 pg/ml on glucose production, including gluconeogenesis, were determined in the conscious, overnight-fasted dog, using a combination of tracer [( 3-3H]glucose and [U-14C]alanine) and arteriovenous difference techniques. Insulin and glucagon were fixed at basal levels using a pancreatic clamp. Plasma glucose levels rose during the 180-min epinephrine infusion by 47 +/- 7, 42 +/- 22, and 74 +/- 25 mg/dl, respectively, in association with increases in hepatic glucose output of 1.04 +/- 0.22, 1.87 +/- 0.23, and 3.70 +/- 0.83 mg.kg-1.min-1 (at 15 min). Blood lactate levels rose by 1.52 +/- 0.24, 4.29 +/- 0.49, and 4.60 +/- 0.45 mmol/l, respectively, by 180 min, despite increases in hepatic uptake of lactate of 3.47 +/- 5.73, 12.83 +/- 3.46, and 37.00 +/- 4.20 mumol.kg-1.min-1. The intrahepatic gluconeogenic efficiency with which the liver converted the incoming alanine to glucose had risen by 84 +/- 40, 77 +/- 24, and 136 +/- 34% at 180 min, respectively. The latter effect plus the effect on net hepatic lactate uptake point to an intrahepatic action of high levels of the hormone in vivo. In conclusion, epinephrine produces dose-dependent increments in overall glucose production, which involve a progressive stimulation of both glycogenolysis (as assessed by glucose production at 15 min) and gluconeogenesis (assessed in the last 30 min of the study). The latter involves a peripheral action of the catecholamine to increase gluconeogenic substrate supply to the liver and may also involve a hepatic effect when high epinephrine levels are present.

Effect of hyperglucagonemia on hepatic glycogenolysis and gluconeogenesis after a prolonged fast

1990 ◽  
Vol 258 (5) ◽  
pp. E841-E849 ◽  
Author(s):  
G. K. Hendrick ◽  
R. T. Frizzell ◽  
P. E. Williams ◽  
A. D. Cherrington
Keyword(s):  
Hepatic Glucose Production ◽  
Hormone Replacement ◽  
Glucose Production ◽  
Hepatic Uptake ◽  
The Other ◽  
Marked Rise ◽  
Glucose Levels ◽  
Hepatic Glucose ◽  
Prolonged Fast ◽  
Plasma Insulin Levels

The aim of this study was to determine if glucagon can stimulate hepatic glucose production in prolonged fasted (7 days) animals. Two protocols were used; in one ("hormone replacement"; n = 4), intraportal basal replacement amounts of insulin and glucagon were given during a somatostatin infusion, whereas, in the other ("glucagon excess"; n = 5) basal insulin was given along with somatostatin and excess glucagon. Plasma insulin levels were similar and constant throughout both protocols (6 +/- 1 microU/ml). The plasma glucagon was basal in the hormone-replacement protocol (49 +/- 9 pg/ml) but rose from 46 +/- 7 to 448 +/- 35 pg/ml (P less than 0.05) in the other protocol. Plasma glucose levels and the rates of glucose production were unchanged during hormone replacement but rose from 100 +/- 5 to 199 +/- 28 mg/dl and from 1.5 +/- 0.1 to a peak of 5.6 +/- 0.2 mg.kg-1.min-1 at 15 min (P less than 0.05) and an eventual plateau of 2.7 +/- 0.2 mg.kg-1.min-1 (P less than 0.05) in response to glucagon excess. Because of the sluggish increase in gluconeogenic parameters, the early marked rise in glucose production was attributable to increased glycogenolysis. Eventually, however, the gluconeogenic rate rose, with net hepatic uptake of alanine increasing 50% and fractional alanine extraction doubling. Gluconeogenic efficiency and conversion increased in response to glucagon excess by 0.30 +/- 0.05 and 159 +/- 48%, respectively, although it should be noted that these parameters rose 0.15 +/- 0.06 and 150 +/- 49% in the hormone-replacement protocol. In conclusion, even after a prolonged fast physiological glucagon can cause hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat

1992 ◽  
Vol 283 (3) ◽  
pp. 759-765 ◽  
Author(s):  
A Gardemann ◽  
Y Watanabe ◽  
V Große ◽  
S Hesse ◽  
K Jungermann
Keyword(s):  
Small Intestine ◽  
Portal Vein ◽  
Superior Mesenteric Artery ◽  
Glucose Uptake ◽  
Mesenteric Artery ◽  
Hepatic Uptake ◽  
Glucose Absorption ◽  
Hepatic Glucose ◽  
Intestinal Glucose Absorption ◽  
Hepatic Glucose Uptake

1. Previous studies have shown that an arterial-to-portal glucose concentration gradient may be an important signal for insulin-dependent net hepatic glucose uptake. It is not known whether intestinal factors also contribute to the regulation of hepatic glucose utilization. This problem was studied in a newly developed model which allows luminal perfusion of the small intestine via the pyloric sphincter and a combined vascular perfusion of the small intestine via the gastroduodenal artery and superior mesenteric artery, and of the liver via the hepatic artery and portal vein. 2. In both the presence and the absence of 1 mM-glutamine in the vascular perfusate, only about 7% of a luminal bolus of 5500 mumol (1 g) of glucose was absorbed by the small intestine, and nothing was taken up by the liver. 3. With small doses of 75-380 mumol (11-55 mg) of luminal glutamine, but not with 300 mumol of alanine, the intestinal absorption of the luminal glucose bolus was increased almost linearly from 7% to a maximum of 40% and the hepatic uptake from 0% to a maximum of 22%. 4. The increase of hepatic glucose uptake caused by luminal glutamine was only observed when the glucose load was applied into the intestinal lumen, rather than into the superior mesenteric artery. 5. The relative hepatic glucose uptake (uptake/portal supply) was enhanced from 0% to 55% with an increase in portal supply by luminal glutamine, whereas with a similar range of portal glucose supply the relative hepatic uptake by the isolated liver, perfused simultaneously via the hepatic artery and portal vein, was slightly decreased, from 20% to 15%. 6. Addition of various amounts of portal glutamine and/or alterations in the Na+ content of the portal perfusate failed to mimic the luminal glutamine-dependent activation of hepatic glucose uptake. Therefore the luminal-glutamine-elicited activation of hepatic glucose uptake was apparently not caused by a simple increase in the portal-arterial glucose gradient, by glutamine itself or by Na(+)-dependent alterations in hepatic cell volume. The results suggest that luminal glutamine caused not only an increase in intestinal glucose absorption by unknown mechanisms but also the generation of one or more humoral or nervous ‘hepatotropic’ signals in the small intestine which enhanced the hepatic uptake of absorbed glucose.

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