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H Orskov

Publications and source records attributed to H Orskov.

At least 127 records · Page 7Linked to original sources

Effects of octreotide on insulin-like growth factor I and metabolic indices in growth hormone-treated growth hormone-deficient patients.

Animals studies have demonstrated that in addition to inhibiting growth hormone (GH) secretion octreotide inhibits in a direct manner hepatic or peripheral insulin-like growth factor I (IGF-I) generation. To test this hypothesis in humans we studied ten GH-deficient patients with frequent blood sampling during 38 h on two occasions. Regular GH therapy was discontinued 72 h prior to each study period. At the start of each study a subcutaneous (sc) injection of GH (3 IU/m2) was given (at 18.00 h). In a single-blinded crossover design, patients received a continuous sc infusion of either octreotide (200 micrograms/24 h) or placebo (saline). The pharmacokinetics of GH were similar on the two occasions. The area under the curve +/- SEM of serum GH was 142.5 +/- 53.6 micrograms.l-1 x h-1 (octreotide) and 144.8 +/- 41.8 micrograms.l-1 x h-1 (placebo), (p = 0.73); Cmax (microgram/l) was 12.5 +/- 1.47 (octreotide) and 12.8 +/- 1.42 (placebo) (p = 0.83), and Tmax (h) was 6.1 +/- 0.97 (octreotide) and 5.2 +/- 0.65 (placebo) (p = 0.49). Growth hormone administration was associated with an increase in serum IGF-I (microgram/l), which was identical during the two studies, from 85.3 +/- 19.4 to 174.25 +/- 30.3 for octreotide and from 97.0 +/- 26.4 to 158.8 +/- 28.2 for placebo. Mean IGF-I levels (microgram/l) were 138.2 +/- 25.1 (octreotide) and 134.5 +/- 28.6 (placebo) (p = 0.78). Similarly, the increase in IGF binding protein 3 (IGFBP-3) levels was identical. Mean IGFBP-3 levels (microgram/l) were 2303 +/- 323 (octreotide) and 2200 +/- 361 (placebo) (p = 0.25).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of growth hormone and thyroxine on kidney insulin-like growth factor-I and renal growth in hypophysectomized rats.

The effects of treatment for 11 days with human growth hormone (hGH; 140 micrograms/day), thyroxine (T4; micrograms/day) and hGH+T4 on renal growth and content of insulin-like growth factor-I (IGF-I) in hypophysectomized rats have been compared with saline-treated hypophysectomized animals and intact control animals. Right kidney weight and kidney weight/body weight ratio remained low in the saline-treated group (313 +/- 9 mg vs 694 +/- 28 mg in controls on day 11, P < 0.001 and 3.4 +/- 0.12 x 10(-3) vs 4.2 +/- 0.10 x 10(-3), P < 0.005 respectively). In T4- and hGH-treated animals, kidney weight gain was similar (to 420 +/- 14 and 450 +/- 22 mg on day 11 respectively, P > 0.05), whilst the increase was greater in the group given hGH+T4 (to 572 +/- 34 mg, P < 0.001 compared with hGH- and T4-treated groups). The kidney weight/body weight ratio became normal in the T4- and hGH+T4-treated animals but remained low in the hGH-treated group. The renal content of IGF-I was low in the saline-treated animals throughout the study (92 +/- 10 ng/g on day 11 vs 219 +/- 8 ng/g in control animals, P < 0.001), but increased to a maximum of 88% above baseline on day 1 in the group given T4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of intravenous glucagon infusion on renal haemodynamics and renal tubular handling of sodium in healthy humans.

The effects of a 2-h intravenous infusion of glucagon 5 ng kg-1 min-1 or placebo on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium handling as judged by the lithium clearance method, and plasma concentrations of angiotensin II (AngII), aldosterone (Aldo), and atrial natriuretic factor (ANF) were investigated in two groups of healthy human volunteers, glucagon group (n = 10), and placebo group (n = 10). Glucagon infusion resulted in a maximal increase in plasma concentrations of glucagon of 400%. GFR increased 5.9% (range 1.3-12.4, p < 0.001) through the whole infusion period, whereas RPF only increased transiently during the first hour of infusion 6.5% (range 2.6-15.3, p < 0.05). Whereas filtered load of sodium increased significantly in response to glucagon infusion (p < 0.001), urinary sodium excretion was unchanged. Neither of these variables were affected by placebo. As judged from assessments of tubular sodium handling derived from the renal clearance of lithium, the increased filtered load of sodium resulted in an increase in the output of sodium from the proximal tubules of a similar magnitude, and an increase in absolute reabsorption of sodium in the distal tubules totally counterbalancing this increased input to the distal tubules. These alterations in tubular sodium handling did not involve Ang II, Aldo, or ANF. We conclude that an increase in plasma concentration of glucagon within the physiological range is capable of inducing a small and sustained increase in GFR, whereas RPF increases only transiently.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of growth hormone on the inflammatory activity of experimental colitis in rats.

The effect of daily treatment with 2.0 mg biosynthetic human growth hormone per kilogram body weight or isotonic NaCl (controls) on experimental colitis was investigated in rats. Colonic inflammation was induced by instillation of trinitrobenzene sulfonic acid (TNB) intraluminally into the left colon. Untreated NaCl-instilled rats were used for comparison with intact colon. Four days after TNB instillation the growth hormone-treated rats had lower macroscopic and microscopic damage scores and less infiltration of neutrophils, measured as myeloperoxidase activity (MPO), than controls. The biomechanical properties of the colon showed that the breaking strength and energy absorption were reduced in the control rats with colitis compared with intact colon, whereas the rats treated with growth hormone had unchanged strength and energy absorption. The differences in MPO activity, damage scores, and biomechanical properties were associated with a higher concentration of insulin-like growth factor I in serum from growth hormone-treated rats after 4 days than controls. Finally, the growth hormone-treated rats regained their initial body weight after 7 days, in contrast to the body weight of control rats, which remained 11% lower than their initial body weight.

Animals↗

Estimates of insulin action in normal, obese and NIDDM man: comparison of insulin and glucose infusion test, CIGMA, minimal model and glucose clamp techniques.

Many methods of varying complexity are available for the measurement of insulin resistance (action) in man. No study has previously compared several of these in the same subjects to establish which is the most appropriate for routine use. We have, therefore, compared six methods: the hyperinsulinemic eu(iso)-glycaemic clamp (Eu), insulin glucose infusion test (IGI), hyperglycaemic clamp (Hy), continuous infusion of glucose with model assessment (CIGMA), minimal model (Min) and modified minimal model (Mod). Nineteen subjects with varying degrees of glucose tolerance were studied. Eight normal (BMI 22.5 +/- 1.5 kg/m2), six obese (BMI 38 +/- 5 kg/m2) and five NIDDM subjects (BMI 27 +/- 3 kg/m2) were investigated, in a randomized fashion, on separate days. The ratio of metabolic clearance rate of glucose (MCRG) and Insulin (I) was used as the measure of insulin action during Eu, Hy and IGI. Si was calculated as the index of insulin sensitivity from (Min) and (Mod) and CIGMA was obtained as previously described. MCRG was converted to Si to allow for direct comparison with (Min). Methods requiring incremental endogenous insulin secretion (which was highly variable) to calculate an index of insulin action (Si Min, Si Hy and CIGMA) failed to find an overall difference between groups. Only Si Eu (p = 0.007) and Si IGI (p = 0.001) demonstrated a significant overall group difference when Si was used. When MCRG/I was used, Eu, IGI and Hy were able to distinguish a significant overall group difference. With the exception of CIGMA and SiHy all other methods found a significant difference in insulin action between normals and NIDDM subjects. Only Eu and IGI could distinguish obese from normal, while only Si Min, could distinguish obese from NIDDM subjects. Eu and IGI were the only methods to be significantly correlated: normals Rs = 0.75, p < 0.05, obese Rs = 0.9, p < 0.05, and NIDDM Rs = 1.0, p < 0.05. In conclusion we have demonstrated that: 1) The insulin-glucose infusion test and the eu(iso)glycaemic clamp were significantly correlated in normals, obese and NIDDM subjects. 2) Only the eu(iso)glycaemic clamp and insulin glucose infusion test could significantly separate obese from normal subjects. 3) the IGI appears to be a practical, simple and precise method for measuring in vivo insulin action in man and gives results closely similar to those found with the hyperinsulinemic eu(iso)glycaemic clamp.

Adult↗

Acute effects of graded alcohol intake on glucose, insulin and free fatty acid levels in non-insulin-dependent diabetic subjects.

Alcohol-induced hypoglycaemia is a well-known phenomenon in insulin-treated diabetic subjects. Less attention has been paid to the impact of alcohol on blood glucose and insulin responses in non-insulin dependent diabetic subjects. The aim of this study was to investigate the acute metabolic effects of different alcohol contents added to a non-alcohol beer in 10 non-insulin-dependent diabetes mellitus (NIDDM) subjects. The patients received 500 ml non-alcohol beer with an alcohol percentage (v/v) of 0 (A), 2.7 (B), and 5.4 (C), implying identical contents of ingredients except for alcohol. Blood glucose (mean +/- SE) responses were similar in the three situations (395 +/- 59, 365 +/- 86 and 261 +/- 26 mmol/l x 240 min). In contrast, the incremental insulin response areas increased dose dependently to alcohol (5430 +/- 1158, 9336 +/- 2172 and 12336 +/- 2922 pmol/l x 240 min) and showed a linear correlation (r = 0.39; P < 0.03). The average suppression of serum free fatty acid was similar in the three situations (72.4 +/- 4.4%, 76.3 +/- 6.0% and 68.2 +/- 6.3%). In conclusion, intake of small amounts of alcohol does not acutely deteriorate the glycaemic control in NIDDM. The fact that alcohol results in a dose-related elevation in insulin levels with unaltered blood glucose and free fatty acid responses in NIDDM points to an aggravation of insulin resistance.

Aged↗

Transient increase in renal insulin-like growth factor binding proteins during initial kidney hypertrophy in experimental diabetes in rats.

The insulin-like growth factors, insulin-like growth factor I and insulin-like growth factor II are bound to six distinct classes of insulin-like growth factor binding proteins (IGFBPs) in the circulation and in extracellular fluids. Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I suggestive of a renotropic function for insulin-like growth factor I. In order to examine a possible involvement of IGFBPs in initial diabetic kidney growth and in kidney insulin-like growth factor I accumulation, we studied rat kidney IGFBPs by ligand blotting during the first 4 days after induction of diabetes. Six distinct bands were identified in kidney and liver tissue with apparent molecular weight values of 38-47 (doublet), 34, 30, 24 and 20 kDa. The 38-47 kDa doublet band probably corresponds to the insulin-like growth factor binding subunit of IGFBP-3, the 24 kDa band to IGFBP-4 and the 30 kDa band to IGFBP-1 and/or IGFBP-2, as these IGFBPs in rats have similar molecular weight. In untreated diabetic rats a transient increase in the kidney 30 kDa band was demonstrable 24 h after induction of diabetes with a maximal rise (two-fold) after 48 h, followed by a decrease to baseline values after 4 days. In untreated diabetic rats the 38-47 kDa doublet band also increased (two-fold) in kidney during the first 2 days after induction of diabetes, followed by a subsequent decrease. Insulin-treatment prevented both the increase in the 30 kDa and in the 38-47 kDa bands.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term efficacy and tolerability of octreotide treatment in acromegaly.

Twenty-five acromegalic patients were studied during 6 years of treatment with octreotide, with a particular focus on the following parameters: (1) Administration schedule: in 10 patients, continuous subcutaneous (SC) octreotide infusion was compared with injections of octreotide at three dose levels (100, 250, and 1,500 micrograms/24 h) and was found to induce a greater and less-fluctuating 24-hour growth hormone (GH) suppression. (2) Carbohydrate tolerance: average 24-hour blood glucose levels were unaffected by octreotide, regardless of administration schedule. Oral carbohydrate tolerance and intravenous (IV) glucose tolerance were unaffected by continuous octreotide infusion. However, octreotide injection given shortly before the tests reduced carbohydrate tolerance. (3) Thyroid function: octreotide and somatostatin acutely reduce the response of thyroid-stimulating hormone (TSH) to thyrotropin-releasing hormone (TRH). After a few days of treatment, it was demonstrated that octreotide slightly inhibits iodothyronine deiodination and induces a transient reduction in serum triiodothyronine (T3), rapidly compensated for by a persistent slight elevation of serum TSH. (4) Fat absorption was estimated as 24-hour fecal fat content and found to be in the same high-normal range before and after octreotide treatment. Vitamin K and D absorption were unaffected by octreotide. The incidence of gallstone formation was not greater than in the general Danish population, possibly due to the schedule used for octreotide injections. (5) Foot volume was regularly estimated and found to decrease with time, on average by 12% during the first 18 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗

Octreotide and diabetes: theoretical and experimental aspects.

Diabetes is characterized by paradoxical hypersomatotropinemia and hyperglucagonemia. The latter appears to enhance the tendency in imperfect metabolic control to reduce nitrogen balance, and the former appears to accelerate the deterioration of carbohydrate and lipid metabolism, and also to induce peripheral insulin resistance and hyperinsulinemia. In addition to direct metabolic effects, increasing evidence points to an association between hypersomatotropinemia and a number of metabolically dependent, characteristic functional abnormalities linked to the development of late diabetic manifestations. These include increased capillary fragility, lipid and hemostatic aberrations, tissue hyperperfusion, including increased cardiac output and renal plasma flow, and kidney hypertrophy. In theory, octreotide's actions could reduce these aberrations, and, in fact, this has been confirmed in recent experimental trials.

Animals↗

Preliminary results with Sandostatin nasal powder in acromegalic patients.

This report details the first half of a double-blind, crossover sequence (Latin square) study of local and hormonal effects of nasally insufflated Sandostatin compared with those of subcutaneously injected Sandostatin. Nine of the planned 16 patients have been studied. They received a single application of 0.5, 1.0, and 2.0 mg Sandostatin as nasal powder and 0.1 mg by subcutaneous (SC) injection. The results indicate that absorption from the nasal epithelium occurs after approximately 10 minutes and comprises approximately 20% of the dose administered. This indicates that peak serum Sandostatin values occur very rapidly, ie, 10 minutes after application. After approximately 2 hours, the serum disappearance rates are similar to those obtained after SC injection. The suppressive effect on serum growth hormone (GH) levels is equal with the two forms of application and suggests that future clinical treatment with an intranasal application of 0.5 mg thrice daily is feasible. No side effects were noted apart from an immediate swelling of nasal mucosa, which receded gradually over the following 2 hours. This was either unnoticed or considered insignificant by the patients and will probably be deemed harmless by the rhinologist in eventual long-term clinical trials.

Absorption↗

The ketosis-resistance in fibro-calculous-pancreatic-diabetes. 1. Clinical observations and endocrine-metabolic measurements during oral glucose tolerance test.

We measured circulating levels of C-peptide, pancreatic glucagon, cortisol, growth hormone and metabolites (glucose, non-esterified fatty acids, glycerol and 3-hydroxybutyrate) in fibro-calculous-pancreatic diabetic (FCPD, n = 28), insulin-dependent diabetic (IDDM, n = 28) and non-diabetic control (n = 27) subjects during an oral glucose tolerance test. There was no difference in the two diabetic groups in age (FCPD 24 +/- 2, IDDM 21 +/- 2 years, mean +/- SEM), BMI (FCPD 16.0 +/- 0.6, IDDM 15.7 +/- 0.4 kg/m2), triceps skinfold thickness (FCPD 8 +/- 1, IDDM 7 +/- 1 mm), glycaemic status (fasting plasma glucose, FCPD 12.5 +/- 1.5, IDDM 14.5 +/- 1.2 mmol/l), fasting plasma C-peptide (FCPD 0.13 +/- 0.03, IDDM 0.08 +/- 0.01 nmol/l), peak plasma C-peptide during OGTT (FCPD 0.36 +/- 0.10, IDDM 0.08 +/- 0.03 nmol/l) and fasting plasma glucagon (FCPD 35 +/- 4, IDDM 37 +/- 4 ng/l). FCPD patients, however, showed lower circulating concentrations of non-esterified fatty acids (0.73 +/- 0.11 mmol/l), glycerol (0.11 +/- 0.02 mmol/l) and 3-hydroxybutyrate (0.15 +/- 0.03 mmol/l) compared to IDDM patients (1.13 +/- 0.14, 0.25 +/- 0.05 and 0.29 +/- 0.08 mmol/l, respectively). This could be due to enhanced sensitivity of adipose tissue lipolysis to the suppressive action of circulating insulin and possibly also to insensitivity of hepatic ketogenesis to glucagon. Our results also demonstrate preservation of alpha-cell function in FCPD patients when beta-cell function is severely diminished, suggesting a more selective beta-cell dysfunction or destruction than hitherto believed.

3-Hydroxybutyric Acid↗

Growth hormone secretory capacity and serum insulin-like growth factor I levels in primary infertile, anovulatory women with regular menses.

OBJECTIVE: To test the hypothesis that anovulation and infertility in women is associated with an impaired secretory capacity for growth hormone (GH). DESIGN: Comparison of the hormonal and metabolic response to two GH stimulation tests in a patient group and in a control group. SETTING: Outpatients and healthy volunteers studied at a clinical research unit of a university hospital. PATIENTS, PARTICIPANTS: Eight infertile, anovulatory women (luteal phase serum progesterone [P] less than 25 nmol/L) with regular cyclic bleeding. Eight age- and body mass index-matched healthy volunteers with luteal phase serum P levels greater than 25 nmol/L. INTERVENTIONS: After an overnight fast, each subject underwent a standardized GH stimulation test composed of sequential arginine infusion and heat exposure on days 5 to 8 of the menstrual cycle. MAIN OUTCOME MEASURES: Serum GH, insulin-like growth factor I (IGF-I), insulin and non-esterified fatty acids (NEFA). RESULTS: Serum GH increased in both groups but was significantly lower in the study group (P less than 0.03). No difference was found in the circulating levels of IGF-I, insulin, and NEFA. CONCLUSIONS: Relative GH insufficiency seems to be present in these patients, but the clinical significance of this finding remains to be elucidated.

Adult↗

Octreotide administration in diabetic rats: effects on renal hypertrophy and urinary albumin excretion.

Initial renal hypertrophy in experimental diabetes is prevented by administration of a long-acting somatostatin analogue octreotide (SMS). To investigate the long-term effects of SMS on renal hypertrophy and urinary albumin excretion (UAE), streptozotocin-diabetic and non-diabetic rats were treated with two daily subcutaneous injections of SMS (100 micrograms x 2) for six months. Untreated diabetic and non-diabetic animals were used as reference groups. No differences were seen between the two diabetic groups in respect to body weight, food intake, blood glucose levels, urinary glucose output, hemoglobin A1C(HbA1C), fructosamine, serum growth hormone (rGH) or creatinine clearance, but kidney weight (896 +/- 36 vs. 1000 +/- 24 mg, P less than 0.02), UAE (417 +/- 131 vs. 1098 +/- 187 micrograms/24 hr, P less than 0.02), kidney insulin-like growth factor I (IGF-I) (167 +/- 16 vs. 239 +/- 17 ng/g, P less than 0.01) and serum IGF-I (301 +/- 26 vs. 407 +/- 17 micrograms/liter, P less than 0.01) were all reduced in the SMS-treated diabetic animals when compared to the untreated diabetic group. In non-diabetic rats SMS reduced body weight (274 +/- 3 vs. 293 +/- 5 g, P less than 0.01), kidney weight (695 +/- 9 vs. 764 +/- 17 mg, P less than 0.01), UAE (83 +/- 29 vs. 364 +/- 114 micrograms/24 hr, P less than 0.02), kidney IGF-I (202 +/- 12 vs. 280 +/- 12 ng/g, P less than 0.01), serum IGF-I (428 +/- 21 vs. 601 +/- 54 micrograms/liter, P less than 0.01) and serum rGH (67 +/- 6 vs. 126 +/- 27 micrograms/liter, P less than 0.05) when compared to untreated controls. When kidney weights were expressed in relation to body weight no difference was found between SMS-treated and untreated controls, while the difference between SMS-treated and untreated diabetic animals was still present (P less than 0.01). In conclusion, chronic administration of SMS has abating effects on diabetic renal hypertrophy and UAE, and thus indicates that SMS may reduce development of diabetic kidney lesions in experimental diabetes. The long-term suppressive effects of SMS on renal enlargement and UAE may in part be mediated through reduction in circulating and kidney IGF-I levels.

Albuminuria↗

SMS 201-995 and thyroid function in acromegaly: acute, intermediate and long-term effects.

The acute (TRH-stimulation test), intermediate (0-6 days administration), and long-term (0-30 months administration) effects of SMS 201-995 (octreotide) treatment on thyroid function were studied. Subcutaneous injection of 100 micrograms SMS 201-995 one hour before 200 micrograms TRH intravenously reduced serum TSH response area by more than 50% in 8 healthy volunteers. After 3 days of continuous subcutaneous infusion (CSI) of SMS 201-995 in 9 acromegalic patients (100 micrograms/24 h) a slight but significant decrease in serum total triiodothyronine (TT3) and a concomitant increase in serum TSH were demonstrated, indicating an initial inhibitory effect on peripheral deiodination of thyroxine. After a further 3 days treatment serum T3 and TSH had returned to prevalues. Six of the nine acromegalics were treated with SMS 201-995 (100-1500 micrograms/24 h) and admitted for diurnal hormone profiles on 13 occasions over 30 months. Apart from a barely significant increase in serum TSH, no changes in thyroid function were noted. The study was especially designed to detect minute changes over time in thyroid hormones. The only long-term effect of SMS 201-995 was the barely significant clinically irrelevant increase in serum TSH, possibly caused by a slight inhibition of peripheral deiodination of thyroxine.

Acromegaly↗

A plea for consistent reliability in ambulatory blood pressure monitors: a reminder.

OBJECTIVE: To compare three different software versions [read-only memory (ROM) versions 1.22, 1.24 and 1.28] of the SpaceLabs model 90202 ambulatory blood pressure monitor. DESIGN: Simultaneous measurements in a two-arm crossover design. METHODS: Ten measurements each in 14 normotensive persons were performed to compare each pair of monitors. The results were corrected according to the deviation from a mercury column. The systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP) was noted and the factor K = (MAP - DBP)/(SBP - DBP) was calculated. RESULTS: The K factor in the two older ROM versions was close to 0.25, with no statistically significant difference. In contrast the K factor was higher in the most recent ROM version than in one of the previous versions. This could be explained by a 5.4 mmHg increase in MAP found by the new version. A significant difference in blood pressure was observed even between two monitors with the same ROM version. CONCLUSION: Unnotified changes in the software version in the SpaceLabs 90202 monitor operating by an oscillometric technique seriously affect the reliability of MAP measurements. Whenever possible in clinical trials the same monitor should be used for the same patient on each occasion. The industry should inform clinicians of the consequences of updating apparently identical monitors.

Blood Pressure↗

Effects of growth hormone on growth and muscle Na(+)-K+ pump concentration in K(+)-deficient rats.

K(+)-deficient rats and control rats were injected for 16 days with saline or human growth hormone (hGH, 200 micrograms/day). hGH treatment of K(+)-deficient rats resulted in increased weight gain and soleus muscle weight. Extensor digitorum longus (EDL) muscle weight and tail and tibia length were unchanged. In control rats, hGH induced an increase in all weight and length parameters. K+ deficiency was associated with reduced serum insulin-like growth factor I (IGF-I) and serum insulin but unchanged total 3,5,3'-triiodothyronine (TT3) and total thyroxine. hGH treatment of the K(+)-deficient rats restored serum IGF-I, but not serum insulin, and decreased TT3. In saline-treated K(+)-deficient rats [3H]ouabain binding site concentration decreased by 44 and 39% in soleus and EDL muscle, respectively, as compared with the saline-treated controls. hGH had no effect on the [3H]ouabain binding site concentration in the K(+)-deficient group, but, in control rats, increases of 11 and 8% were observed in soleus and EDL muscle, respectively. When the increase in muscle weight was taken into account, this amounted to relative increases of 24 and 30%, respectively. Low circulating GH and IGF-I levels are not the sole explanation for the growth retardation in K+ deficiency. GH/IGF-I stimulate the synthesis of Na(+)-K+ pumps in rats with an otherwise normal hormonal status.

Animals↗