help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Clowes, J. A.
Right arrow Articles by Blumsohn, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clowes, J. A.
Right arrow Articles by Blumsohn, A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*GLUCOSE
*PARATHYROID HORMONE
The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 7 3324-3329
Copyright © 2002 by The Endocrine Society

Other Original Articles

Acute Changes of Bone Turnover and PTH Induced by Insulin and Glucose: Euglycemic and Hypoglycemic Hyperinsulinemic Clamp Studies

Jackie A. Clowes, Robert T. Robinson, Simon R. Heller, Richard Eastell and Aubrey Blumsohn

Bone Metabolism Group (J.A.C., R.E., A.B.) and Diabetes and Endocrinology Group (R.T.R., S.R.H.), Division of Clinical Sciences (North), University of Sheffield, S5 7 AU Sheffield, United Kingdom

Address all correspondence and requests for reprints to: Dr. Aubrey Blumsohn, M.D., Ph.D., MRCPath, University of Sheffield, Division of Clinical Sciences (North), Northern General Hospital, Herries Road, Sheffield, S5 7 AU, United Kingdom. E-mail: . ablumsohn{at}sheffield.ac.uk

Abstract

Bone turnover is acutely suppressed after feeding or oral glucose. Insulin infusion suppresses bone turnover and might mediate this effect, but this is confounded by a possible direct effect of hypoglycemia. We examined the effect of euglycemic hyperinsulinemia and hypoglycemic hyperinsulinemia on bone turnover using an insulin clamp. Sixteen men participated in this double-blind crossover study. Clamp induction involved infusion of insulin (80 mU/m2·min) while maintaining euglycemia (5 mmol/liter) for 40 min with a variable rate dextrose infusion. Glucose was lowered to 2.5 mmol/liter (hypoglycemic clamp) or maintained at 5 mmol/liter (euglycemic clamp) for a further 105 min. Nine controls received a matched saline infusion. Measurements included serum C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide, osteocalcin, and PTH.

Induction of hyperinsulinemia resulted in a reduction in PTH (27% ± 5; P < 0.01), but no significant change in bone turnover from baseline. Hypoglycemic clamp resulted in suppression of serum C-terminal telopeptide of type I collagen by 34% ± 3, procollagen type I N-terminal propeptide by 15% ± 1, osteocalcin by 5% ± 1, and PTH by a further 12% ± 5 (all P < 0.05). By contrast, there was no significant change in any marker of bone turnover during euglycemic clamp.

Postprandial hyperinsulinemia is unlikely to explain the acute suppression of bone turnover with feeding. The reduction in bone turnover during hypoglycemia may be related to hypoglycemia itself, acute changes in PTH, or other hormones released in response to hypoglycemia.

RECENT OBSERVATIONS SUGGEST that bone turnover is suppressed after feeding (1) or after an oral glucose load (2). This change in bone turnover is rapid and may be observed over minutes to hours in human studies (1, 2). The suppression in bone resorption after a standard 75-g glucose tolerance test is approximately 50% using serum C-terminal telopeptide of type I collagen (sßCTX) as a marker of bone collagen degradation (2). The postprandial suppression of bone turnover is observed using several different markers of bone formation and resorption (1). In addition, the pronounced circadian rhythm of bone turnover is attenuated by fasting (3, 4) suggesting that this rhythm is mediated, at least in part, by food intake.

The factors that mediate the acute effect of food or glucose ingestion on bone turnover are unknown. Possible mechanisms include the postprandial rise in insulin, a direct effect of glucose on bone metabolism, or other associated endocrine responses. One recent study found that intravenous administration of insulin results in a decrease in bone resorption (2), suggesting insulin as a possible mediator. However, this design does not differentiate the direct effect of insulin from the effect of insulin-induced hypoglycemia on bone.

We examined the effect of euglycemic hyperinsulinemia on bone turnover using an insulin clamp technique. This technique enables examination of the independent effect of glucose and insulin by simultaneous infusion of glucose and insulin. The blood glucose is maintained at a predetermined value while maintaining a constant insulin concentration. The primary aim of this study was to determine the acute effect of hyperinsulinemia alone on bone turnover, while maintaining steady-state euglycemia. We also examined the acute effect of hypoglycemic hyperinsulinemia on bone turnover using a hypoglycemic clamp.

Subjects and Methods

Subjects

Twenty-five healthy men (mean age, 23 yr; range, 18–35 yr) were recruited. Subjects were excluded if they had any disease known to affect bone metabolism or were taking any medications. Three subjects were current smokers. Mean body mass index was 23.0 kg/m2 (range, 19.1–29.0 kg/m2). The study was performed in accordance with current guidelines on Good Clinical Practice and the Declaration of Helsinki. All subjects gave written informed consent, and the study was approved by the North Sheffield Research Ethics Committee.

Protocol

On each study day, volunteers attended the investigation unit after an overnight fast from 2400 h. All subjects remained fasting throughout the study. Subjects were blinded to the study protocol, and all measurements were performed double blind. Sixteen subjects were studied in a crossover design with a euglycemic hyperinsulinemic clamp protocol or a hypoglycemic hyperinsulinemic clamp on two separate days. The order of study (hypoglycemic/euglycemic or euglycemic/hypoglycemic) was randomized at the first visit. Nine control subjects received a matched saline infusion but no glucose or intravenous insulin.

Subjects were placed in a semirecumbent position, and a cannula was inserted into the nondominant antecubital fossa for infusion of saline, glucose, or insulin. Blood glucose was monitored using arterialized venous samples from a second cannula at 5 min intervals throughout the clamp protocol. Cannulae were kept patent using 0.9% saline.

During the clamp protocols, subjects received a continuous infusion of soluble insulin (Human Actrapid, Novo Nordisk Pharma Ltd., Crawley, UK). Insulin was infused at a fixed rate (80 mU/m2·min). Glucose (20%) was infused at a variable rate to maintain blood glucose at the desired level. The infusion rate was adjusted every 5 min according to a predefined algorithm.

The induction phase of the clamp protocols began at 0900 h. The blood glucose was adjusted to 5.0 mmol/liter during the 40-min induction period for both hypoglycemic and euglycemic clamps. Steady-state was achieved within 40 min in all subjects. For purposes of statistical analysis, all results were expressed relative to this time point (time 0). For the euglycemic clamp, blood glucose was maintained at 5 mmol/liter for the duration of the clamp. For the hypoglycemic clamp, glucose was lowered in a stepwise manner from time 0 to reach 2.5 mmol/liter within 60 min. Steady-state hypoglycemia was maintained for a further 60 min. Activation of counter-regulatory responses to hypoglycemia including the suppression of insulin secretion and stimulation of glucagon release typically occurs at plasma glucose below 3.5 mmol/liter in normal subjects (5). During the control protocol, subjects received a matched infusion of saline (200 ml/h).

Plasma samples were collected at -40, 0, 15, 30, 45, 60, 75, 90, 105, and 120 min. All samples were frozen within 1 h and stored under identical conditions at -70 C.

Biochemical methods

Glucose was measured using a glucose oxidase method (YSI 2300, YSI, Inc., Yellow Springs, OH). Total insulin was measured by RIA using a double-antibody technique. The intra-assay coefficient of variation was 6%. Total calcium was measured using dry-slide technology (Ortho Clinical Diagnostics, Rochester, NY). Intact PTH was measured using an immunochemiluminometric assay (Roche Elecsys, Hoffman-LaRoche Inc., Penzberg, Germany).

Bone resorption was assessed using serum ß C-terminal crosslinked telopeptide of type I collagen (sßCTX; ß-Crosslaps/serum; Roche Elecsys). Bone formation was assessed using serum procollagen type I N-terminal propeptide (PINP; Roche Elecsys) and osteocalcin (OC; Roche Elecsys). The analytical coefficients of variation for sßCTX, PINP, and OC were less than 5%, less than 1%, and less than 2%, respectively, over the relevant analytical range. All assays were performed blind to the randomization.

Statistical analysis

Results for markers of bone turnover were expressed as a percentage of baseline (time 0 min). Responses were tested using repeated measures ANOVA with time as the within-subjects factor. The Huynh-Feldt correction was applied when the sphericity assumption was not met. Post hoc comparisons were performed using paired contrasts to compare the measurement at each time with baseline using Bonferroni adjustment for multiple comparisons. Area under the curve (AUC) was calculated for each protocol and analyte and compared using t tests. Statistical analyses were performed using Statgraphics Plus Version 4 (Manugistics, Inc., Rockville, MD) and SPSS 10.0 (SPSS, Inc., Chicago, IL).

Results

Baseline characteristics for the 25 subjects are shown in Table 1Go. The absolute values for insulin and glucose during the induction of hyperinsulinemia and subsequent clamp protocols are shown in Fig. 1Go. In the control protocol, there was no significant change in insulin or glucose with time (P > 0.05). Insulin increased 13-fold from a fasting (-40 min) value of 72 pmol/liter to 945 pmol/liter (P < 0.001) during the induction phase (-40 to 0 min) of the hypoglycemic and euglycemic clamps. Plasma glucose remained stable (P > 0.05) during induction of hyperinsulinemia. Plasma insulin remained stable during the clamp (0 to 120 min), and the change in plasma insulin with time was identical in hypoglycemic and euglycemic protocols (AUC; paired t test; P > 0.05). All subjects exhibited a marked adrenergic response, and some subjects exhibited neuroglycopenic symptoms. There was a 3-fold increase in cortisol during the hypoglycemic clamp (repeated measures ANOVA effect of time P < 0.01; Fig. 2Go and Table 2Go).


View this table:
[in this window]
[in a new window]
  		Table 1. Baseline characteristics of subjects in the control group and hypoglycemic hyperinsulinemic and euglycemic hyperinsulinemic clamp protocols

 


View larger version (20K):
[in this window]
[in a new window]
  		Figure 1. Absolute values for insulin and glucose during the induction phase and the euglycemic hyperinsulinemic and hypoglycemic hyperinsulinemic clamps. The arrow indicates the onset of steady-state hypoglycemia (2.5 mmol/liter) in the hypoglycemic clamp. *, P < 0.05; **, P < 0.01, comparison with fasting baseline after adjustment for multiple comparisons.

 


View larger version (17K):
[in this window]
[in a new window]
  		Figure 2. Change in cortisol during the euglycemic hyperinsulinemic and hypoglycemic hyperinsulinemic clamp protocols. The arrow indicates the onset of steady-state hypoglycemia in the hypoglycemic clamp. **, P < 0.01 comparison with onset of clamp (time 0) after adjustment for multiple comparisons. AUC differed between the euglycemic vs. hypoglycemic clamp (P < 0.0001).

 

View this table:
[in this window]
[in a new window]
  		Table 2. Percentage change in bone turnover markers and biochemical parameters in the control group and clamp protocols during induction of hyperinsulinemia, and sustained euglycemic and hypoglycemic hyperinsulinemic clamp

 
There was no change in any bone turnover marker in the control group during the induction phase (P > 0.05; Fig. 3Go). Change in bone turnover during induction of hyperinsulinemia in the clamp protocols is shown in Fig. 3Go and summarized in Table 2Go. There was no change from baseline in sßCTX, PINP, and OC during the induction of hyperinsulinemia (-40 to 0 min; paired t test; P > 0.05; Fig. 3Go). However, this change was significant for PINP and OC when compared with controls (Table 2Go).



View larger version (26K):
[in this window]
[in a new window]
  		Figure 3. Percentage change in bone markers (sßCTX, PINP, and OC) in the euglycemic hyperinsulinemic and hypoglycemic hyperinsulinemic clamps (A–C) and in the control protocol (D). The arrow indicates the onset of steady-state hypoglycemia in the hypoglycemic clamp. *, P < 0.05; **, P < 0.01 comparison with onset of clamp (time 0) after adjustment for multiple comparisons. There was no significant overall change in any bone turnover marker in the control group (repeated measures ANOVA; P > 0.05). During the euglycemic clamp, there was no significant decrease in sßCTX, PINP, or OC (repeated measures ANOVA effect of time P > 0.05). The hypoglycemic clamp was associated with a significant reduction in sßCTX, PINP, and OC (repeated measures ANOVA effect of time P < 0.01).

 
During the euglycemic clamp, there was no significant reduction in sßCTX, PINP, or OC (repeated measures ANOVA effect of time P > 0.05; Fig. 3Go). There was also no significant difference between the euglycemic clamp and controls (P > 0.05; Table 2Go).

In contrast, the hypoglycemic clamp was associated with a significant reduction in sßCTX, PINP, and OC (repeated measures ANOVA effect of time P < 0.01; Fig. 3Go). Percentage change at time 105 min (Table 2Go) and AUC differed significantly between the euglycemic and hypoglycemic clamp protocols for sßCTX and PINP (P < 0.001) but not for OC (P > 0.05).

Change in PTH and serum calcium is shown in Fig. 4Go and Table 2Go. Induction of hyperinsulinemia (-40 to 0 min) resulted in a transient 27% reduction in PTH (P < 0.05), which partially recovered during the euglycemic hyperinsulinemic clamp (Fig. 4Go). In contrast, during hyperinsulinemic hypoglycemia the reduction in PTH was progressive.



View larger version (14K):
[in this window]
[in a new window]
  		Figure 4. Change in PTH and total calcium in the euglycemic hyperinsulinemic and hypoglycemic hyperinsulinemic clamp protocols. The arrow indicates the onset of steady-state hypoglycemia in the hypoglycemic clamp. *, P < 0.05; **, P < 0.01 comparison with onset of clamp (time 0) after adjustment for multiple comparisons. AUC differed between the euglycemic vs. hypoglycemic clamp for PTH (P < 0.0001).

 
Discussion

There is increasing evidence that intake of a variety of nutrients, including a mixed meal (1), glucose (2), or calcium (6, 7, 8), results in acute suppression of bone turnover. The pronounced circadian rhythm of bone turnover is attenuated by fasting (3, 4). The mechanism for the effect of feeding on bone turnover is unknown, and it is not clear whether different nutrients operate via a common mechanism.

The acute effect of feeding on bone resorption could be attributed to postprandial changes in glucose, insulin, or other postprandial endocrine changes. The insulin receptor is expressed by osteoblasts and osteoclast-like cells (9, 10), and insulin may modulate bone turnover directly (10). Hyperglycemia with hyperinsulinemia could also have indirect effects on bone turnover by stimulating intestinal calcium absorption (11) and renal calcium excretion (12). Postprandial changes in renal calcium handling are probably mediated by insulin (13, 14). There is, however, some evidence that insulin might contribute to the acute effect of feeding on bone resorption. Intravenous administration of insulin does decrease bone resorption (2). However, such studies are confounded by a possible indirect effect of insulin-induced hypoglycemia on bone, and the decrease observed is less than would be expected if insulin were the sole mediator (2).

In this study, we used a hyperinsulinemic clamp protocol to investigate the relative contribution of insulin and glucose on bone turnover. There was no significant change in bone turnover in the control group during the induction phase. Infusion of insulin had no effect on bone turnover when euglycemia was maintained. This suggests that insulin does not play an important role in mediating the acute effect of feeding on bone resorption.

Plasma insulin concentrations attained in this study are higher than those observed physiologically in response to a meal and approximately twice that observed after a standard glucose tolerance test. Mediators other than insulin are therefore likely to explain the acute decrease in bone turnover after a mixed meal (1) or glucose intake (2). Several other hormones such as amylin, glucose-dependent insulinotropic peptide, and calcitonin may be secreted in response to nutrient intake, and several of these have been shown to regulate bone turnover in vitro (15, 16, 17) and in vivo (18, 19, 20, 21, 22). Catecholamines and glucagon are unlikely mediators of the suppression of bone turnover after feeding because they are released in the late postprandial phase (23, 24).

In contrast to the effect of euglycemic hyperinsulinemia, hypoglycemia results in a decrease in bone resorption and formation despite equivalent insulin concentrations. This suggests that the reduction in bone turnover previously observed after an insulin infusion (2) is likely to be related to hypoglycemia itself.

There are a number of possible mechanisms for the reduction in bone turnover during hypoglycemia including: 1) a direct effect of hypoglycemia on osteoclast and osteoblast function, 2) other counter-regulatory hormones released in response to hypoglycemia, 3) changes in the metabolism of bone turnover markers, and 4) the hypoglycemia-induced reduction in plasma PTH. The most likely mechanism is hypoglycemia-induced suppression of osteoclast and osteoblast function because these cells are sensitive to glucose supply (25, 26, 27). The glucocorticoid and adrenergic response to hypoglycemia is unlikely to mediate the decrease in bone resorption with hypoglycemia. If anything, catecholamines appear to increase bone resorption (28, 29). Acute changes in serum cortisol do not alter bone resorption (30, 31). It is possible that glucagon might inhibit bone resorption indirectly by stimulating the secretion of calcitonin (32).

The apparent decrease in bone turnover observed during hypoglycemia could also be due to decreased clearance or metabolism of these markers. The factors influencing metabolism of these analytes are poorly understood. Concordance of response between different analytes would suggest a genuine effect because these are removed from the extravascular compartment by different mechanisms. In a previous study, a variety of bone turnover markers changed in parallel after feeding, with the exception of bone alkaline phosphatase, which has a long half-life (1).

We observed an acute decrease in PTH during the induction phase of the clamp, with partial recovery during sustained euglycemic hyperinsulinemia. The changes we observed are similar to those observed previously (33, 34, 35), including the recovery with sustained hyperinsulinemia (34). The insulin-induced change in PTH is independent of serum calcium or ionized calcium (34). There are several mediators apart from calcium, which are likely to regulate PTH secretion in this context. Glucose (36) and insulin (33, 37) may modulate PTH secretion directly. There are insulin receptors in parathyroid tissue, and insulin modulates PTH secretion in vitro (36, 37, 38). Insulin has also been shown to modulate PTH secretion acutely in vivo (33).

Hypoglycemic hyperinsulinemia was associated with a marked reduction in PTH secretion. This has also been observed in insulin-induced hypoglycemia (37), and is unlikely to be due to changes in serum calcium (37). Glucose is known to have a direct effect on PTH secretion in vitro (36). There is conflicting evidence relating to the effect of catecholamines on PTH secretion (39).

The role of PTH as a mediator of acute food-induced changes in bone turnover is uncertain. Fasting results in attenuation of the circadian rhythm of PTH secretion (3, 40). However, the suppression of PTH by calcium infusion does not alter the circadian rhythm in bone turnover (41), and reversal of the nocturnal increase in PTH by timed evening calcium administration only partially suppresses the nocturnal peak in bone resorption (6).

In conclusion, we have shown firstly that insulin has a relatively small acute effect on bone turnover in vivo. Postprandial hyperinsulinemia is therefore unlikely to explain the acute suppression of bone turnover observed with feeding. Secondly, hypoglycemia results in an acute suppression of bone turnover. The reduction in bone turnover during hypoglycemia may be related to hypoglycemia itself, acute changes in PTH, or other hormones released in response to hypoglycemia.

Acknowledgments

We thank the volunteers for generously participating in this study, Alison Eagleton for assisting with measurement of markers of bone turnover, the University of Newcastle for assisting with measurement of insulin, Roche Diagnostics (Penzberg, Germany) for providing reagents for the measurement of bone turnover markers and PTH, and Diabetes UK for supporting the clinical protocol.

Footnotes

This work was supported by Diabetes UK, which provided funding toward the cost of the clinical study. J.A.C. was supported by a fellowship from the National Health Service Executive.

Abbreviations: AUC, Area under the curve; OC, osteocalcin; PINP, serum procollagen type I N-terminal propeptide; sßCTX, serum Cterminal telopeptide of type I collagen.

Received October 18, 2001.

Accepted March 28, 2002.

References

  1. Clowes JA, Yap TS, Li J, Hoyle N, Blumsohn A, Hannon RA, Eastell R The effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone, in press
  2. Bjarnason NH, Henriksen EE, Alexandersen P, Christgau S, Henriksen DB, Christiansen C 2002 Mechanism of circadian variation in bone resorption. Bone 30:307–313[Medline]
  3. Schlemmer A, Hassager C 1999 Acute fasting diminishes the circadian rhythm of biochemical markers of bone resorption. Eur J Endocrinol 140:332–337[Abstract]
  4. Christgau S 2000 Circadian variation in serum CrossLaps concentration is reduced in fasting individuals. Clin Chem 46:431[Free Full Text]
  5. Schwartz NS, Clutter WE, Shah SD, Cryer PE 1987 Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest 79:777–781
  6. Blumsohn A, Herrington K, Hannon RA, Shao P, Eyre DR, Eastell R 1994 The effect of calcium supplementation on the circadian rhythm of bone resorption. J Clin Endocrinol Metab 79:730–735[Abstract]
  7. Horowitz M, Wishart JM, Goh D, Morris HA, Need AG, Nordin BE 1994 Oral calcium suppresses biochemical markers of bone resorption in normal men. Am J Clin Nutr 60:965–968[Abstract/Free Full Text]
  8. Villa I, Saccon B, Rubinacci A 2000 Response to acute osteoclast activity inhibition assessed by the determination of C-telopeptide of type I collagen in serum. Clin Chem 46:567–569
  9. Pun KK, Lau P, Ho PW 1989 The characterization, regulation, and function of insulin receptors on osteoblast-like clonal osteosarcoma cell line. J Bone Miner Res 4:853–862[Medline]
  10. Thomas DM, Hards DK, Rogers SD, Ng KW, Best JD 1996 Insulin receptor expression in bone. J Bone Miner Res 11:1312–1320[Medline]
  11. Rumenapf G, Schmidtler J, Schwille PO 1990 Intestinal calcium absorption during hyperinsulinemic euglycemic glucose clamp in healthy humans. Calcif Tissue Int 46:73–79[Medline]
  12. Lemann Jr J, Lennon EJ, Piering WR, Prien Jr EL, Ricanati ES 1970 Evidence that glucose ingestion inhibits net renal tubular reabsorption of calcium and magnesium in man. J Lab Clin Med 75:578–585[Medline]
  13. DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ 1975 The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. J Clin Invest 55:845–855
  14. DeFronzo RA, Goldberg M, Agus ZS 1976 The effects of glucose and insulin on renal electrolyte transport. J Clin Invest 58:83–90
  15. Cornish J, Callon KE, Lin CQ, Xiao CL, Gamble GD, Cooper GJ, Reid IR 1999 Comparison of the effects of calcitonin gene-related peptide and amylin on osteoblasts. J Bone Miner Res 14:1302–1309[CrossRef][Medline]
  16. Bollag RJ, Zhong Q, Phillips P, Min L, Zhong L, Cameron R, Mulloy AL, Rasmussen H, Qin F, Ding KH, Isales CM 2000 Osteoblast-derived cells express functional glucose-dependent insulinotropic peptide receptors. Endocrinology 141:1228–1235[Abstract/Free Full Text]
  17. Cornish J, Callon KE, Bava U, Kamona SA, Cooper GJ, Reid IR 2001 Effects of calcitonin, amylin, and calcitonin gene-related peptide on osteoclast development. Bone 29:162–168[Medline]
  18. Thamsborg G, Jensen JE, Kollerup G, Hauge EM, Melsen F, Sorensen OH 1996 Effect of nasal salmon calcitonin on bone remodeling and bone mass in postmenopausal osteoporosis. Bone 18:207–212[Medline]
  19. Schwille PO, Schmiedl A, Herrmann U, Schwille R, Fink E, Manoharan M 1997 Acute oral calcium-sodium citrate load in healthy males. Effects on acid-base and mineral metabolism, oxalate and other risk factors of stone formation in urine. Methods Find Exp Clin Pharmacol 19:417–427[Medline]
  20. Cornish J, Callon KE, King AR, Cooper GJ, Reid IR 1998 Systemic administration of amylin increases bone mass, linear growth, and adiposity in adult male mice. Am J Physiol 275:E694–E699
  21. Cornish J, Callon KE, Gasser JA, Bava U, Gardiner EM, Coy DH, Cooper GJ, Reid IR 2000 Systemic administration of a novel octapeptide, amylin-(1—8), increases bone volume in male mice. Am J Physiol Endocrinol Metab 279:E730–E735
  22. Bollag RJ, Zhong Q, Ding KH, Phillips P, Zhong L, Qin F, Cranford J, Mulloy AL, Cameron R, Isales CM 2001 Glucose-dependent insulinotropic peptide is an integrative hormone with osteotropic effects. Mol Cell Endocrinol 177:35–41[CrossRef][Medline]
  23. Tse TF, Clutter WE, Shah SD, Miller JP, Cryer PE 1983 Neuroendocrine responses to glucose ingestion in man. Specificity, temporal relationships, and quantitative aspects. J Clin Invest 72:270–277
  24. Tse TF, Clutter WE, Shah SD, Cryer PE 1983 Mechanisms of postprandial glucose counterregulation in man. Physiologic roles of glucagon and epinephrine vis-a-vis insulin in the prevention of hypoglycemia late after glucose ingestion. J Clin Invest 72:278–286
  25. Williams JP, Blair HC, McDonald JM, McKenna MA, Jordan SE, Williford J, Hardy RW 1997 Regulation of osteoclastic bone resorption by glucose. Biochem Biophys Res Commun 235:646–651[CrossRef][Medline]
  26. Terada M, Inaba M, Yano Y, Hasuma T, Nishizawa Y, Morii H, Otani S 1998 Growth-inhibitory effect of a high glucose concentration on osteoblast-like cells. Bone 22:17–23[Medline]
  27. Balint E, Szabo P, Marshall CF, Sprague SM 2001 Glucose-induced inhibition of in vitro bone mineralization. Bone 28:21–28[Medline]
  28. Moore RE, Smith CK, Bailey CS, Voelkel EF, Tashjian Jr AH 1993 Characterization of ß-adrenergic receptors on rat and human osteoblast-like cells and demonstration that ß-receptor agonists can stimulate bone resorption in organ culture. Bone Miner 23:301–315[Medline]
  29. Frediani U, Becherini L, Lasagni L, Tanini A, Brandi ML 1996 Catecholamines modulate growth and differentiation of human preosteoclastic cells. Osteoporos Int 6:14–21[CrossRef][Medline]
  30. Schlemmer A, Hassager C, Alexandersen P, Fledelius C, Pedersen BJ, Kristensen IO, Christiansen C 1997 Circadian variation in bone resorption is not related to serum cortisol. Bone 21:83–88[Medline]
  31. Heshmati HM, Riggs BL, Burritt MF, McAlister CA, Wollan PC, Khosla S 1998 Effects of the circadian variation in serum cortisol on markers of bone turnover and calcium homeostasis in normal postmenopausal women. J Clin Endocrinol Metab 83:751–756[Abstract/Free Full Text]
  32. Stern PH, Bell NH 1970 Effects of glucagon on serum calcium in the rat and on bone resorption in tissue culture. Endocrinology 87:111–117[Abstract/Free Full Text]
  33. Nowicki M, Fliser D, Fode P, Ritz E 1996 Changes in plasma phosphate levels influence insulin sensitivity under euglycemic conditions. J Clin Endocrinol Metab 81:156–159[Abstract]
  34. Nowicki M, Kokot F, Surdacki A 1998 The influence of hyperinsulinaemia on calcium-phosphate metabolism in renal failure. Nephrol Dial Transplant 13:2566–2571[Abstract/Free Full Text]
  35. Ohno Y, Suzuki H, Yamakawa H, Nakamura M, Saruta T 2000 Insulin sensitivity and calcium homeostasis in young, lean, normotensive male subjects. Hypertens Res 23:433–444[Medline]
  36. Sugimoto T, Ritter C, Morrissey J, Hayes C, Slatopolsky E 1990 Effects of high concentrations of glucose on PTH secretion in parathyroid cells. Kidney Int 37:1522–1527[Medline]
  37. Shearing CH, Ashby JP, Hepburn DA, Fisher BM, Frier BM 1992 Suppression of plasma intact parathyroid hormone levels during insulin- induced hypoglycemia in humans. J Clin Endocrinol Metab 74:1270–1276[Abstract]
  38. Hinton DA, MacGregor RR 1991 Effects of insulin on the synthesis, intracellular degradation, and secretion of parathormone. Endocrinology 128:488–495[Abstract/Free Full Text]
  39. Body JJ, Cryer PE, Offord KP, Heath III H 1983 Epinephrine is a hypophosphatemic hormone in man. Physiological effects of circulating epinephrine on plasma calcium, magnesium, phosphorus, parathyroid hormone, and calcitonin. J Clin Invest 71:572–578
  40. Fraser WD, Logue FC, Christie JP, Cameron DA, O’Reilly DS, Beastall GH 1994 Alteration of the circadian rhythm of intact parathyroid hormone following a 96-hour fast. Clin Endocrinol (Oxf) 40:523–528[Medline]
  41. Ledger GA, Burritt MF, Kao PC, O’Fallon WM, Riggs BL, Khosla S 1995 Role of parathyroid hormone in mediating nocturnal and age-related increases in bone resorption. J Clin Endocrinol Metab 80:3304–3310[Abstract]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
Q. Zhong, T. Itokawa, S. Sridhar, K.-H. Ding, D. Xie, B. Kang, W. B. Bollag, R. J. Bollag, M. Hamrick, K. Insogna, et al.
Effects of glucose-dependent insulinotropic peptide on osteoclast function
Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E543 - E548.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
F. Galluzzi, S. Stagi, R. Salti, S. Toni, E. Piscitelli, G. Simonini, F. Falcini, and F. Chiarelli
Osteoprotegerin serum levels in children with type 1 diabetes: a potential modulating role in bone status
Eur. J. Endocrinol., December 1, 2005; 153(6): 879 - 885.
[Abstract] [Full Text] [PDF]

Home page
 IBMS BoneKEyHome page
D. B. Henriksen
The Gut Feeling of Bone Remodeling
IBMS BoneKEy, November 1, 2005; 2(11): 16 - 23.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Clowes, J. A.
Right arrow Articles by Blumsohn, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clowes, J. A.
Right arrow Articles by Blumsohn, A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*GLUCOSE
*PARATHYROID HORMONE

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals