EFFECTS OF GROWTH HORMONE AND OF HYPOPHYSECTOMY ON THE RELEASE OF INSULIN FROM RAT PANCREAS IN VITRO

1965 ◽  
Vol 50 (2) ◽  
pp. 202-212 ◽  
Author(s):  
P. R. Bouman ◽  
R. S. Bosboom
Keyword(s):  
Growth Hormone ◽  
Insulin Release ◽  
Direct Action ◽  
Pancreatic Tissue ◽  
Glucose Stimulation ◽  
Rat Pancreas ◽  
Hypophysectomized Rats ◽  
Low Glucose

ABSTRACT The release of insulin from ligated rat pancreas in vitro was measured after pre-incubation of the tissue at either high or low glucose concentrations. Insulin release was estimated by determining the glucose uptake of rat hemidiaphragms after joint incubation with the pancreatic tissue. Addition of bovine growth hormone (GH) to the pre-incubation medium in a concentration of 0.1 mg/ml significantly increased the response to glucose stimulation. Pancreatic tissue of hypophysectomized rats failed to respond to GH in vitro, although previous hypophysectomy was shown to reduce the response to glucose stimulation. Pretreatment of hypophysectomized rats with GH in doses which restored the growth rate to normal, caused the reappearance of the effect of GH in vitro. The glucose sensitivity of pancreatic tissue was also increased by pretreatment with GH in vivo alone. It is concluded from these findings that GH may increase the sensitivity of the β-cells to glucose by direct action. Since hypophysectomy exerts an opposite effect, it is suggested that physiological levels of endogenous GH may be involved in the regulation of insulin release.

Reduced and S-carboxymethylated human growth hormone: a probe for diabetogenic action

1984 ◽  
Vol 247 (5) ◽  
pp. E639-E644
Author(s):  
C. M. Cameron ◽  
J. L. Kostyo ◽  
J. A. Rillema ◽  
S. E. Gennick
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Mouse Mammary Gland ◽  
Amino Acid Incorporation ◽  
Acid Incorporation ◽  
Hypophysectomized Rats

The biological activity profile of reduced and S-carboxymethylated human growth hormone (RCM-hGH) was determined to establish its suitability for study of the diabetogenic property of hGH. RCM-hGH was found to have greatly attenuated in vivo growth-promoting activity in the 9-day weight-gain test in hypophysectomized rats (approximately 1%) and to have a similar low order of in vitro activity in stimulating amino acid incorporation into the protein of the isolated rat diaphragm. RCM-hGH also only had approximately 1% of the in vitro insulin-like activity of the native hormone on isolated adipose tissue from hypophysectomized rats. In contrast, RCM-hGH retained substantial in vivo diabetogenic activity in the ob/ob mouse, appearing to have approximately 50% of the activity of the native hormone. RCM-hGH was also found to retain significant, although attenuated (25%), in vitro lactogenic activity when tested for the ability to stimulate amino acid incorporation into a casein-rich protein fraction in mouse mammary gland explants. Because RCM-hGH exhibits a high degree of diabetogenic activity, although lacking significant anabolic or insulin-like activities, it will be useful as a "monovalent" probe for the study of the molecular mechanism of the diabetogenic action of GH.

Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat

1996 ◽  
Vol 135 (4) ◽  
pp. 481-488 ◽  
Author(s):  
Antonio Torsello ◽  
Roberta Grilli ◽  
Marina Luoni ◽  
Margherita Guidi ◽  
Maria Cristina Ghigo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Mechanism Of Action ◽  
Direct Action ◽  
Male Rats ◽  
Surgical Ablation ◽  
Adult Rats ◽  
Gh Secretion ◽  
Plasma Gh

Torsello A, Grilli R, Luoni M, Guidi M, Ghigo MC, Wehrenberg WB, Deghenghi R, Müller EE, Locatelli V. Mechanism of action of Hexarelin. I. Growth hormone-releasing activity in the rat. Eur J Endocrinol 1996;135:481–8. ISSN 0804–4643 We have reported Hexarelin (HEXA), an analog of growth hormone-releasing peptide 6 (GHRP-6), potently stimulates growth hormone (GH) secretion in infant and adult rats. This study was undertaken to further investigate Hexarelin's mechanisms of action. In 10-day-old pups, treatments with HEXA (80 μg/kg, b.i.d.) for 3–10 days significantly enhanced, in a time-related fashion, the GH response to an acute HEXA challenge. Qualitatively similar effects were elicited in pups passively immunized against growth hormone-releasing hormone (GHRH) from birth. In adult male rats, a 5-day pretreatment with HEXA (150 μg/kg, b.i.d.) did not enhance the effect of the acute challenge, and the same pattern was present after a 5-day pretreatment in male rats with surgical ablation of the mediobasal hypothalamus (MBH-ablated rats). In addition, in adult sham-operated rats, Hexarelin (300 μg/kg, iv) induced a GH response greater (p < 0.05) than that induced by GHRH (2 μg/kg, iv). However, in MBH-ablated rats 7 days after surgery, GHRH was significantly (p < 0.05) more effective than HEXA, and 30 days after surgery HEXA and GHRH evoked similar rises of plasma GH. Finally, the in vitro Hexarelin (10−6 mol/l) effect was transient while GHRH (10−8 mol/l) induced a longer lasting and greater GH release. Three different mechanisms, not mutually exclusive, are postulated for Hexarelin stimulation of GH secretion in vivo: a direct action on the pituitary, though of minor relevance; an indirect action that involves release of GHRH, of relevance only in adult rats; and an action through the release of a still unknown hypothalamic "factor", which in infant and adult rats elicits GH release acting sinergistically with GHRH. Antonio Torsello, Department of Pharmacology, via Vanvitelli 32, 20129 Milano, Italy

IN VITRO AND IN VIVO EFFECT OF GROWTH HORMONE ON ALDOSTERONE SECRETION

1960 ◽  
Vol 38 (1) ◽  
pp. 1069-1075
Author(s):  
O. J. Lucis ◽  
E. H. Venning
Keyword(s):  
Growth Hormone ◽  
Adrenal Gland ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Hypophysectomized Rats

Porcine, monkey, and human growth hormone have no effect on the in vitro secretion of aldosterone by the rat adrenal gland. When monkey growth hormone is injected into hypophysectomized rats, the adrenals of these animals secrete, under in vitro conditions, increased amounts of aldosterone with no change in the secretion rate of corticosterone. The plasma of these rats contains a substance which appears to stimulate the secretion of aldosterone in the adrenals of normal rats.

Active transport of calcium by intestine: effects of hypophysectomy and growth hormone

1962 ◽  
Vol 203 (5) ◽  
pp. 873-880 ◽  
Author(s):  
James D. Finkelstein ◽  
David Schachter
Keyword(s):  
Growth Hormone ◽  
Active Transport ◽  
Electrical Potential ◽  
Potential Gradient ◽  
Initial Increase ◽  
Bovine Growth Hormone ◽  
Hypophysectomized Rats ◽  
Rat Duodenum

The effects of hypophysectomy on active transport of calcium in vitro by everted gut sacs of rat duodenum are 1) an initial increase 4–5 days postoperatively and 2) a marked decrease 2–3 weeks postoperatively. The defect in transport results from reduction in the unidirectional transfers of Ca toward the serosa, and both steps in the transport (mucosal uptake and transfer to serosal surface) are impaired. Hypophysectomy also decreases iron transport (duodenal gut sacs), decreases l-proline transfer less strikingly (ileal gut sacs), increases d-galactose transport (jejunal gut sacs), and does not appear to influence either the electrical potential gradient from mucosa to serosa or the net flux of sodium. Treatment of hypophysectomized rats with a preparation of bovine growth hormone restores transfer mechanisms for calcium and iron. Ovine prolactin is also active in restoring the Ca mechanism, whereas other pituitary and nonpituitary hormones are not. Cortisone, l-thyroxin, and estradiol decrease Ca transport further in hypophysectomized rats. Absorption of Ca from loops of rat duodenum in vivo is also decreased 2 weeks after hypophysectomy and can be increased by prior treatment with bovine growth hormone.

IN VITRO AND IN VIVO EFFECT OF GROWTH HORMONE ON ALDOSTERONE SECRETION

1960 ◽  
Vol 38 (10) ◽  
pp. 1069-1075 ◽  
Author(s):  
O. J. Lucis ◽  
E. H. Venning
Keyword(s):  
Growth Hormone ◽  
Adrenal Gland ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Hypophysectomized Rats

Porcine, monkey, and human growth hormone have no effect on the in vitro secretion of aldosterone by the rat adrenal gland. When monkey growth hormone is injected into hypophysectomized rats, the adrenals of these animals secrete, under in vitro conditions, increased amounts of aldosterone with no change in the secretion rate of corticosterone. The plasma of these rats contains a substance which appears to stimulate the secretion of aldosterone in the adrenals of normal rats.

scholarly journals Pancreatic Islets Accumulate Cadmium in a Rodent Model of Cadmium-Induced Hyperglycemia

2020 ◽  
Vol 22 (1) ◽  
pp. 360
Author(s):  
Ryan Fitzgerald ◽  
Andrew Olsen ◽  
Jessica Nguyen ◽  
Winifred Wong ◽  
Malek El Muayed ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Fasting Blood Glucose ◽  
Pancreatic Tissue ◽  
Experimental Models ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Low Glucose

Cadmium (Cd) is an anthropogenic as well as a naturally occurring toxicant associated with prediabetes and T2DM in humans and experimental models of Cd exposure. However, relatively few studies have examined the mechanism(s) of Cd-induced hyperglycemia. The purpose of this study was to examine the role of pancreatic islets in Cd-induced hyperglycemia. Male Sprague–Dawley rats were given daily subcutaneous doses of Cd at 0.6 mg/kg over 12 weeks. There was a resulting time-dependent increase in fasting blood glucose and altered insulin release in vitro. Islets isolated from control (saline-treated) and Cd-treated animals were incubated in low (0.5 mg/mL) or high (3 mg/mL) glucose conditions. Islets from 12 week Cd-treated animals had significantly less glucose-stimulated insulin release compared to islets from saline-treated control animals. The actual Cd content of isolated islets was 5 fold higher than the whole pancreas (endocrine + exocrine) and roughly 70% of that present in the renal cortex. Interestingly, islets isolated from Cd-treated animals and incubated in high glucose conditions contained significantly less Cd and zinc than those incubated in low glucose. These results show that within whole pancreatic tissue, Cd selectively accumulates in pancreatic islets and causes altered islet function that likely contributes to dysglycemia.

EFFECTS OF GROWTH HORMONE ON THE METABOLISM OF THE ISOLATED LEVATOR ANI MUSCLE OF THE RAT

1967 ◽  
Vol 56 (3_Suppl) ◽  
pp. S15-S25 ◽  
Author(s):  
A. Arvill ◽  
Å. Hjalmarson
Keyword(s):  
Growth Hormone ◽  
Distribution Ratio ◽  
Accumulation Rate ◽  
Levator Ani ◽  
Male Rats ◽  
Normal Male ◽  
Levator Ani Muscle ◽  
Hypophysectomized Rats

ABSTRACT The effects of growth hormone (GH) were investigated in the levator ani muscle and the diaphragm from hypophysectomized and from normal male rats. GH was added to the incubation media and/or injected daily for four days to the rats before the in vitro experiments. GH, added in vitro, stimulated the rate of accumulation of D-xylose-14C in the two muscles from hypophysectomized but not from normal rats. GH, in vitro, increased the distribution ratio of α-aminoisobutyric acid-14C (AIB-14C) in the diaphragm from hypophysectomized rats to a much higher degree than in muscles from normal rats. In vivo injections of GH to hypophysectomized rats which were not stimulating in itself, made the diaphragm insensitive to GH added in vitro. In the levator ani muscle, however, a different effect was obtained on the AIB-14C distribution ratio. GH in vitro did not stimulate muscles from hypophysectomized rats more than those from normal rats. Furthermore, administration of GH to hypophysectomized rats, which not was stimulating in itself, gave an additional effect with GH in vitro in this muscle. The accumulation rate as well as the incorporation into protein of glycine-3H increased in both muscles from hypophysectomized rats after in vivo as well as in vitro administration of GH. The results are discussed in connection to our present knowledge of the different effects of GH.

SENSITIVITY OF THE RAT DIAPHRAGM TO GROWTH HORMONE

1967 ◽  
Vol 56 (2) ◽  
pp. 347-358 ◽  
Author(s):  
Å. Hjalmarson ◽  
K. Ahrén
Keyword(s):  
Growth Hormone ◽  
Fold Increase ◽  
Inhibitory Effect ◽  
Acute Administration ◽  
Transport Mechanisms ◽  
Intracellular Accumulation ◽  
Clinical Observations ◽  
Hypophysectomized Rats

ABSTRACT The in vivo and in vitro effects of bovine growth hormone (GH) on the rate of intracellular accumulation of D-xylose and α-aminoisobutyric acid (AIB) were studied in the intact rat hemidiaphragm preparation. GH was added in vitro or injected intravenously (i. v.) to hypophysectomized rats 45 min before incubation. It markedly increased the accumulation of both D-xylose-14C and AIB-14C by the isolated diaphragm. This stimulatory effect of GH was almost completely abolished by pretreatment of the rats with GH, either intramuscularly for 4 days or i. v. 16 hours before the in vitro experiment. An i. v. injection of GH (10 μg) to hypophysectomized rats 45 or 90 min before incubation gave a two-fold increase in the rate of AIB uptake by the isolated diaphragm while a similar injection 3½, 24 or 38 hours before incubation did not produce such stimulation. These injections, however, significantly decreased the sensitivity of the diaphragm to GH, added later in vitro. This type of inhibitory effect was seen after a single i. v. injection of as little as 1.0 μg of GH. The results indicate that acute administration of GH to hypophysectomized rats may first produce a stimulatory effect for 2–3 hours, which is then followed by an inhibitory phase lasting for as long as 35 hours. The nature of these two effects of GH are discussed in connection with other experimental and clinical observations on the diversity of the GH action. It is concluded that the contrasting effects of GH found in the present study on the isolated diaphragm may be due, at least in part, to changes in the transport mechanisms of the cell membrane to amino acids and sugars.

Rapid depletion of somatostatin in isolated mouse pancreatic islets after treatment with cysteamine

1985 ◽  
Vol 110 (2) ◽  
pp. 227-231 ◽  
Author(s):  
Birger Petersson ◽  
Claes Hellerström
Keyword(s):  
Pancreatic Islets ◽  
Insulin Release ◽  
Basal Insulin ◽  
Glucose Stimulation ◽  
Isolated Pancreatic Islets ◽  
Basal Release ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets

Abstract. Cysteamine (CSH; β-mercaptoethylamine) is known to deplete pancreatic somatostatin without affecting the insulin or glucagon content. It may therefore be useful for studies of intra-islet regulation of hormone release. In the present study injection of CSH (60 mg/kg body weight) to mice decreased the somatostatin content of their isolated pancreatic islets to 50% in 1 h and 30% in 4 h as compared to islets of non-injected controls. Exposure of isolated mouse islets to CSH (100 μg/ml) for either 0.5 h followed by incubation in control medium for 3.5 h, or continuously for 4 h, decreased the somatostatin content to about 40% of the controls. There was no change in the islet content of insulin or glucagon. Islets pretreated with CSH (100 μg/ml) for 1 h in vitro showed a decreased glucose stimulation of both oxygen consumption and glucose oxidation. Measurements of insulin release after a similar preincubation of the islets indicated an increased basal release and an attenuated glucose stimulation. It is concluded that CSH rapidly decreases islet somatostatin both in vivo and in vitro. This depletion may lead to a loss of tonic inhibition by islet somatostatin on basal insulin release. It is, however, more plausible that the increased basal insulin release reflected a direct effect of CSH on the islet β-cells.

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