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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 10 3476-3479
Copyright © 1998 by The Endocrine Society

Original Studies

Effect of Growth Hormone (GH) on Serum Concentrations of Leptin: Study in Patients with Acromegaly and GH Deficiency1

Megumi Miyakawa, Toshio Tsushima, Hitomi Murakami, Osamu Isozaki, Hiroshi Demura and Toshiaki Tanaka

Department of Internal Medicine, Institute of Clinical Endocrinology Tokyo Women’s Medical College (M.M., T.Ts., H.M., O.I., H.D.), and the Department of Endocrinology and Metabolism, National Children’s Medical Research Center (T.Ta.), Tokyo, Japan

Address all correspondence and requests for reprints to: Megumi Miyakawa, M.D., Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women’s Medical College, 8–1 Kawada-cho, Tokyo, Japan.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
As leptin, an ob gene product, plays a pivotal role in the regulation of adiposity and energy homeostasis, the level of its expression is likely to fluctuate under various physiological, nutritional, and disease conditions. Reports regarding the effect of GH on serum leptin levels are inconsistent. We have measured serum leptin levels and correlated them with several variables in patients with acromegaly, patients with adult GH deficiency (GHD), and normal controls. In 116 normal subjects, the mean serum concentration of leptin was 5.0 ± 2.8 (mean ± SD) ng/mL in men (n = 42) and 10.7 ± 7.3 ng/mL in women (n = 73), respectively. As reported previously, the leptin levels in women were significantly (P < 0.001) higher than in men, and there was a strong positive correlation between log-transformed serum leptin levels and percent body fat in simple regression analysis (in men: r = 0.606; P < 0.0001; in women: r = 0.707; P < 0.0001). In 36 acromegalic patients, the percent body fat mass was significantly lower than that in normal subjects, and the mean serum leptin level was 2.2 ± 1.8 ng/mL in men (n = 18) and 3.6 ± 2.5 ng/mL in women (n = 18). Analysis of covariance revealed that serum leptin levels in acromegalics were significantly lower than those in normal subjects after correcting percent body fat (P = 0.016 for men and P < 0001 for women). In male patients with GHD (n = 20), the mean percent body fat was significantly (P < 0.05) higher than that in age-matched controls, whereas the value in female GHD patients (n = 15) did not differ from that in age-matched controls. Serum leptin levels in GHD patients were 5.1 ± 2.5 ng/mL in men and 11.5 ± 8.1 ng/mL in women, which were not different from those in normal subjects adjusted for percent body fat mass. In multiple regression analysis models with log-transformed leptin as the dependent variable, gender, percent body fat (or body fat mass), and serum insulin-like growth factor I levels entered the equations at a statistically significant level. These data suggest that excess GH/insulin-like growth factor I reduces serum leptin levels by reducing body fat mass and/or by unknown mechanisms.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
THE ob gene is an adipocyte-specific gene that encodes leptin, a protein that regulates body weight and energy expenditure by acting on the hypothalamus (1). Mutations in the ob gene that result in a lack of circulating leptin cause obesity, and administration of recombinant leptin causes weight loss in mice (2, 3). A number of studies in humans have shown that the abundance leptin messenger ribonucleic acid (mRNA) correlates with body weight (4), and there is a positive correlation between body fat mass and circulating leptin concentrations (4, 5, 6). However, the mechanism by which obesity increases leptin production has not been clarified. Recent in vivo and in vitro studies have shown that insulin (7, 8, 9, 10), glucocorticoids (11, 12), and estrogens (13) are positive regulators of leptin production, whereas ß3-adrenergic stimulators negatively regulate leptin mRNA expression (14). An inhibitory effect has also been reported for androgen (15, 16). The relationship between GH status and leptin production is interesting, because 1) obesity is frequently associated with blunted GH secretion in humans (17); 2) GH has a well described lipolytic action (18); and 3) GH deficiency (GHD) results in increased adiposity with reduced lean body mass that can be restored by GH treatment (19, 20, 21, 22). In contrast, GH excess is associated with decreased body fat mass (23). Furthermore, leptin has been shown to modulate GH secretion in fasted rats (24). Although there are a few reports on the effect of GH on leptin production, the data have been inconsistent (16, 25, 26, 27, 28). We, therefore, examined the serum leptin concentrations in patients with acromegaly characterized by long term GH excess. The results were compared with those in adult patients with GHD and healthy adult controls.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Subjects

Thirty-five adult patients with GHD (20 men and 15 women) and 36 with active acromegaly (18 men and 18 women) were included in this study. GHD was diagnosed by the absence or low response of GH (peak GH value, <5 ng/mL) on at least 2 provocative tests, i.e. the insulin tolerance test, the GHRH test, or the clonidine test, and by low concentrations of serum insulin-like growth factor I (IGF-I). Sixteen of the 38 GHD patients had onset during childhood and had received GH therapy during childhood (duration, 7.8 ± 2.6 yr). The duration of GHD in the 22 adult-onset GHD patients was estimated to be 19.7 ± 13.5 yr, and they had not received GH replacement therapy. Five male patients had isolated GHD, and the remainder had gonadotropin, TSH, ACTH, and antidiuretic hormone deficiencies in various combinations. All patients were receiving appropriate adrenal, thyroidal, or gonadal hormone replacement therapy at the time of this study. The patients with ACTH deficiency and hypothyroidism were treated with cortisol (10–20 mg/day) and T4, respectively. The dose of T4 was adjusted to normalize serum free T4 levels, and serum free T4 concentrations were maintained at 0.9–1.4 ng/dL. Male patients with hypogonadism were receiving treatment with testosterone enanthate (125 mg, im, once every 2 weeks); blood samples were obtained 1–2 weeks after the last injection. All but 3 female patients were being treated with conjugated estrogen with or without dydrogesterone. Acromegaly was diagnosed by clinical features and high serum GH and IGF-I concentrations. Thyroid, adrenal, and gonadal functions were intact in all of the acromegalic patients. One hundred and sixteen normal subjects (73 women, aged 46.5 ± 14.8 yr, and 42 men, aged 46.8 ± 15.1 yr) served as controls. All blood samples were collected between 1300–1500 h, and the serum was stored at -80 C until analysis.

Measurement

The percentage of body fat was calculated by bioelectric impedance (29), which was determined by means of Spectrum II 286 analysis (RJL Systems, Inc., Mt. Clemons, MI). Serum leptin was measured by RIA (Linco Research, Inc., St. Charles, MO) using recombinant human leptin. The limit of detection was 0.5 ng/mL, and the intra- and interassay coefficients of variation were 4.1% and 6.5%, respectively. Serum GH levels were measured with immunoradiometric assay kits (GH kit, Eiken Chemical Co., Tokyo, Japan). Free T4, IGF-I, and urinary C peptide (CPR) were measured with commercial RIA kits [Ortho Clinical Diagnostics Co. (Tokyo, Japan) for free T4, Kailon Co. (Tokyo, Japan) for IGF-I, and Shionogi Pharmaceutical Co. (Tokyo, Japan) for CPR, respectively].

Statistical analysis

Values for outcome measures are reported as the mean ± SD. Leptin values were log transformed to increase the normality of their distribution. Differences in subject characteristics were determined by two-way ANOVA, and analysis of covariance was performed to calculate differences between groups. Simple correlations were assessed for serum leptin levels and percent body fat mass. To determine the independent effects of variables on serum leptin levels, multiple linear regression analyses were performed. Differences between groups were considered significant at P < 0.05. Statistical calculations were made using StatView 4.5 and Super ANOVA software (Abacus Concepts, Berkeley, CA).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Body mass index (BMI), percent body fat mass, serum IGF-I, urinary CPR excretion, and serum leptin levels in normal subjects, patients with acromegaly, and patients with GHD are shown in Table 1Go. There was no significant difference in BMI among these groups in either men or women. Consistent with a previous report (23), the percent body fat mass in both male and female acromegalic patients was significantly lower than that in normal subjects (P < 0.001 and P < 0.005, respectively, by ANOVA). The percent body fat mass in male GHD was not different from the value in the entire group of normal males, but the value was significantly (P < 0.01) higher than that in age-matched normal males (16.5 ± 7.7%; aged 39.2 ± 9.8 yr; n = 20), as previously reported by others (20, 21, 22). In contrast, the value for female GHD was not different from that in the age-matched controls. Serum IGF-I levels in both sexes were higher in acromegaly and lower in GHD than those in normal subjects. Urinary excretion of CPR was significantly higher in acromegalics of both sexes than that in normal subjects (P < 0.05), but there was no difference in the value between normal subjects and patients with GHD.


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  		Table 1. Characteristics in normal subjects and patients with acromegaly and GHD

 
The serum leptin concentrations in normal men and women were 5.0 ± 2.8 (n = 43) and 10.7 ± 7.3 ng/mL (n = 73), respectively. There was no correlation between age and leptin levels in either men or women. The value in premenopausal women was not different from that in postmenopausal women. Acromegalic patients showed significantly (P < 0.001, by ANOVA) lower serum leptin values (2.2 ± 1.8 for men and 3.6 ± 2.5 ng/mL for women) than sex-matched normal subjects. In contrast, there was no significant difference in serum leptin levels between GHD patients and normal subjects of the same gender. In both acromegaly and GHD, the values for women were significantly higher (P = 0.0005 for GHD and P = 0.009 for acromegaly) than those for men.

As shown in Fig. 1Go, log-transformed serum concentrations of leptin in normal subjects correlated positively with body fat mass for both men (r = 0.606; P < 0.0001) and women (r = 0.707; P < 0.0001). Similarly, a strong positive correlation between serum leptin concentrations and BMI was seen in normal subjects (data not shown). A positive correlation between leptin and percent body fat mass was also observed in GHD patients (men: r = 0.562; P = 0.01; women: r = 0.512; P = 0.025). However, these relations were not significant in patients with acromegaly (men: r = 0.367; P = 0.150; women: r = 0.279; P = 0.258) in simple regression analysis. When log-transformed leptin was plotted as a function of fat mass (kilograms) instead of percent body fat, there was no significant correlation between the two variables in acromegalics (men: r = 0.072; P = 0.291; women: r = 0.369; P = 0.144), whereas the correlation was significant in normal subjects (men: r = 0.592; P < 0.0001; women: r = 0.756; P < 0.0001) and in patients with GHD (men: r = 0.597; P = 0.006; women: r = 0.483; P = 0.042).



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  		Figure 1. The relationship between log-transformed serum leptin concentrations and the percentage of body fat mass in normal subjects ({circ}), acromegalic patients (•), and GHD patients ({blacktriangleup}) in women (right panel) and men (left panel). Regression lines for three groups are shown as A (normal), B (acromegalics), and C (GHD). In women, r = 0.707; P < 0.0001 for normal subjects, r = 0.279; P = 0.258 for acromegalics, and r = 0.512; P = 0.025 for GHD patients. In men, r = 0.606; P < 0.0001 for normal subjects, r = 0.367; P = 0.150 for acromegalics, and r = 0.597; P = 0.006 for GHD patients, respectively.

 
As shown in Table 1Go and Fig. 1Go, the percent body fat in acromegaly was very low, especially in male patients. The failure to detect a significant correlation between leptin and body fat mass in acromegalics might be due to the limited range of percent body fat mass. To determine that the acromegalics were different from the normal subjects, analysis of covariance was performed using percent body fat mass and log-transformed leptin, and grouping the normal and the acromegalic subjects. With this model, the leptin levels were significantly lower in both male (P = 0.015) and female acromegalics (P < 0001) after adjusting for percent body fat mass. Again, there was no difference in leptin levels between patients with GHD and normal subjects using this model.

We performed multiple regression analysis with log-transformed leptin as the dependent variable, and gender, percent fat mass, serum IGF-I, and urinary CPR as independent variables (Table 2Go). Gender, percent body fat and IGF-1 significantly accounted for the variability in leptin levels. Similar results were obtained when fat mass (kilograms) instead of percent body fat was added to this model.


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  		Table 2. Multiple regression analyses: correlation between log-transformed leptin and metabolic and hormonal variables

 
A number of reports have shown that insulin is involved in the regulation of leptin production (7, 8, 9, 10). In simple regression analysis, there was a weak, but significant, correlation between urinary CPR and leptin in both normal men (r = 0.468; P = 0.0435) and women (r = 0.369; P = 0.0245), which was consistent with reports that circulating leptin levels are positively related to fasting insulin levels (30). On the other hand, serum leptin levels in neither GHD nor acromegaly correlated with urinary CPR. Furthermore, urinary CPR did not enter the equations at a significant level with the multiple regression analysis, as shown in Table 1Go.


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Consistent with earlier reports, circulating leptin levels in normal subjects was positively correlated with BMI and percent body fat mass (5, 6), and the values were significantly higher in women (31, 32). The higher leptin levels in women were also found in both acromegalic and GHD patients. A recent report suggested a stimulating effect of estrogens on ob gene expression in ovariectomized rats (13), but it is unlikely that estrogens are responsible for the higher leptin levels in women, because circulating leptin concentrations were not different between pre- and postmenopausal women. In vitro experiments have also failed to detect a stimulating effect of estrogens on expression of leptin mRNA in adipocytes. The lower androgen concentrations in females may be responsible for the higher circulating leptin levels (15).

The reported effect of GH on leptin production is inconsistent. Boni-Schnelzler et al. (25) reported that expression of ob mRNA in adipose tissue was markedly suppressed after hypophysectomy in rats, GH infusion had no effect on ob mRNA expression, and IGF-I treatment further suppressed ob mRNA expression. One study in humans also failed to detect any effect of GH on circulating leptin concentrations (26). Conversely, other studies have shown that circulating leptin levels are elevated in patients with GHD compared to those in normal subjects (28), and that long term GH replacement therapy results in a decline in leptin levels (27, 28). The lack of difference in leptin concentrations between GHD patients and normal subjects in the present study is inconsistent with these findings. The reason for this discrepancy is not clear. It could be explained by the difference in the replacement doses of other hormones (glucocorticoids, sex steroids, etc.), the duration or degree of GHD, or the timing of blood sampling.

The data presented here demonstrate the decreased serum leptin levels in active acromegaly. The decreased levels of leptin could be accounted for by decreased body fat mass alone. This is unlikely, however, because leptin levels in acromegaly were lower after adjusting for percent body fat. It appears that factors other than body fat mass are involved in the decreased serum leptin concentrations. The difference in body fat distribution between normal subjects and acromegalics could at least in part contribute to the difference in serum leptin concentrations (32). This possibility remains to be tested.

Numerous studies have shown that insulin stimulates leptin production. Prolonged exposure of cultured human adipocytes to insulin increased leptin production (8), and leptin production was increased during long term hyper-insulinemia induced by insulin infusion (8, 33). Acromegaly is frequently associated with hyperinsulinemia and insulin resistance, and elevated urinary excretion of CPR was also demonstrated in this study. Despite the hyperinsulinemia, serum leptin levels remained low in acromegalic patients. It appears, therefore, that insulin per se is not the major factor responsible for the decreased leptin levels.

A direct effect of GH and IGF-I on leptin regulation of adipocytes is also possible. Reported expression of IGF-I receptors in adipocytes (34) and suppression of leptin mRNA expression by IGF-I in rat adipocytes (25) as well as an inverse correlation between serum IGF-I and leptin levels (35) would suggest that IGF-I is involved in the decreased leptin levels in acromegaly. Multiple regression analysis also showed that serum leptin levels were negatively associated with IGF-I. Alternatively, GH may act on adipocytes directly, because they express GH receptors and respond to GH with increased lipolysis (18). In our preliminary studies, however, exposure of neither GH nor IGF-I to cultured human adipocytes for up to 24 h did not change ob gene expression, whereas dexamethasone significantly increased the expression. Thus, we have not been able to demonstrate a direct effect of GH or IGF-I on expression of leptin mRNA. The possibility remains that the decreased leptin level in acromegaly is mediated by some metabolic factors induced by excess GH/IGF-I. Further studies are required to clarify this point.

In conclusion, the data presented here suggest that excessive GH/IGF-I causes a fall in serum leptin levels at least in part independently of the percent body fat mass and insulin levels.


   Acknowledgments
 
The authors thank Dr. K. Ichihara, Kawasaki Medical School, for assistance with statistics.


   Footnotes
 
1 This work was supported in part by a grant from the Ministry of Health and Welfare of Japan. Back

Received November 18, 1997.

Revised May 28, 1998.

Accepted June 24, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Zhang Y, Proenca R, Maffei M, Barone N, Leopold L, Friedman JM. 1994 Positional cloning of the mouse obese gene and its human homologue. Nature. 372:425–432.[CrossRef][Medline]
  2. Pelleymouter MA, Cullen MJ, Baker MB, et al. 1995 Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 269:540–543.[Abstract/Free Full Text]
  3. Halaas JL, Gajiwala KS, Maffei M, et al. 1995 Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 269:543–546.[Abstract/Free Full Text]
  4. Lonqvist F, Arner P, Nordfors L. Schalling M. 1995 Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med. 1:953–956.[CrossRef][Medline]
  5. Considine RV, Sinha MK, Heiman ML, et al. 1996 Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 334:292–295.[Abstract/Free Full Text]
  6. Maffei M, Halaas JM, Rarussin E, et al. 1995 Measurements of plasma leptin and ob mRNA in obese and weight reduced subjects. Nat Med. 1:1155–1161.[CrossRef][Medline]
  7. Dagogo-Jack S, Fanelli C, Paramore D, et al. 1996 Plasma leptin and insulin relationships in obese and nonobese humans. Diabetes. 45:695–698.[Abstract]
  8. Kolaczynski JW, Nyce MR, Considine RV, et al. 1996 Acute and chronic effect of insulin on leptin production in humans. Studies in vitro and in vivo. Diabetes. 45:699–701.[Abstract]
  9. Segal KR, Landt M, Klein S. 1996 Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes. 45:988–991.[Abstract]
  10. Saladin R, De Vos P, Guerre-Millo M, et al. 1995 Transient increase in obese expression after food intake or insulin administration. Nature. 377:527–529.[CrossRef][Medline]
  11. Larsson H, Ahren BO. 1996 Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women. J Clin Endocrinol Metab. 81:4428–4432.[Abstract]
  12. Slieker LJ, Sloop KW, Surface PL, et al. 1996 Regulation of expression of ob mRNA and protein by glucocorticoids and cAMP. J Biol Chem. 271:5301–5304.[Abstract/Free Full Text]
  13. Shimizu H, Shimomura Y, Nakanishi Y, et al. 1997 Estrogen increases in vivo leptin production in rats and human subjects. J Endocrinol. 154:285–292.[Abstract/Free Full Text]
  14. Mantzoros CS, Qu D, Federich RC, et al. 1996 Activation of ß3 adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice. Diabetes. 45:909–914.[Abstract]
  15. Wabittsch M, Blum WF, Muche R, et al. 1997 Contribution of androgens to the gender difference in leptin production in obese children and adolescents. J Clin Invest. 100:808–813.[Medline]
  16. Nystrom F, Ekman B, Osterlund M, Lindstom T, Ohman KP, Arnqvist HJ. 1997 Serum leptin concentrations in a normal population and in GH deficiency: negative correlation with testosterone in men and effects of GH treatment. Clin Endocrinol (Oxf). 47:191–198.[CrossRef][Medline]
  17. Veldhuis JD, Iranmmanesh A, Ho KKY, et al. 1991 Dual effects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. J Clin Endocrinol Metab. 72:51–59.[Abstract/Free Full Text]
  18. Davidson MB. 1987 Effect of growth hormone on carbohydrate and lipid metabolism. Endocr Rev. 8:115–131.[Abstract/Free Full Text]
  19. Salomon F, Cuneo RC, Hesp R, Sonksen PH. 1989 The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 321:1797–1803.[Abstract]
  20. De Boer H, Blok GJ, Voerman HJ, De Vries PMJM, Van der Veen EA. 1992 Body composition in adult growth hormone-deficient men, assessed by anthrometry and bioimpedance analysis. J Clin Endocrinol Metab. 75:833–837.[Abstract]
  21. Binnerts A, Deurenberg P, Swart GR, Wlson JHP, Lamberts SWJ. 1992 Body composition in growth hormone-deficient adults. Am J Clin Nutr. 55:918–923.[Abstract/Free Full Text]
  22. Rosen T, Boseaeus I, Tolli J, Lindstedt G, Sonksen PH. 1993 Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency. Clin Endocrinol (Oxf). 38:63–71.[Medline]
  23. Bengtsson BA, Brummer R-J M, Eden S, Bosaeus I. 1989 Body composition in acromegaly. Clin Endocrinol (Oxf). 30:121–130.[Medline]
  24. Carro E, Senaris R, Considine RV, Casanueva FF, Dieguez C. 1997 Regulation of in vivo growth hormone secretion by leptin. Endocrinology. 138:2203–2206.[Abstract/Free Full Text]
  25. Boni-Schnetzler M, Gosteli-Peter MA, Moritz W, et al. 1996 Reduced ob mRNA in hypophysectomised rats is not restored by growth hormone (GH), but further suppressed by exogenously administered insulin-like growth factor (IGF) I. Biochem Biophys Res Commun. 225:296–301.[CrossRef][Medline]
  26. Berneis K, Vosmeer S, Keller U. 1996 Effects of glucocorticoids and of growth hormone on serum leptin concentrations in man. Eur J Endocrinol. 135:663–665.[Abstract/Free Full Text]
  27. Florkowski CNM, Collier GR, Zimmet PZ, et al. 1997 Low-dose growth hormone replacement lowers plasma leptin and fat stores without affecting body mass index in adults with growth hormone deficiency. Clin Endocrinol (Oxf). 45:769–773.
  28. Fisker S, Vahl N, Hansen TB, et al. 1997 Serum leptin is increased in growth hormone-deficient adults: relationship to body composition and effects of placebo-controlled growth hormone therapy for 1 year. Metabolism. 46:812–817.[CrossRef][Medline]
  29. Likaski HC, Bolochuk WW, Hall CB, Siders WA. 1988 Validation of tetrapolar bioelectrical impedance method to assess human body composition. J Appl Physiol. 60:1327–1332.
  30. Kennedy A, Gettys TW, Watson P, et al. 1997 The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab. 82:1293–1300.[Abstract/Free Full Text]
  31. Saad MF, Damani S, Gingerich RL, et al. 1997 Sexual dimorphism in plasma leptin concentration. J Clin Endocrinol Metab. 82:579–584.[Abstract/Free Full Text]
  32. Nagy TR, Gower BA, Trowbridge CA, Dezenberg C, Shewchuk RA, Goran MI. 1997 Effects of gender, ethnicity, body composition, and fat distribution on serum leptin concentrations in children. J Clin Endocrinol Metab. 82:2148–2152.[Abstract/Free Full Text]
  33. Utriainen T, Malmstrom R, Makimattila S, Yki-Jarvinen H. 1996 Supra-physiological hyperinsulinemia increases plasma leptin concentrations after 4h in normal subjects. Diabetes. 45:1364–1366.[Abstract]
  34. Desautels M, Bhaumick B, Ram JI. 1996 Comparison of trophic effects of norepinephrine, insulin, and IGF-I in mouse brown adipocytes. Am J Physiol. 270:R1287–R1295.
  35. Paolisso G, Ammendola S, Buono AD, et al. 1997 Serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in healthy centenarians: relationship with plasma leptin and lipid concentrations, insulin action, and cognitive function. J Clin Endocrinol Metab. 82:2204–2209.[Abstract/Free Full Text]



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