Increasing Insulin Resistance Is Associated with a Decrease in Leydig Cell Testosterone Secretion in Men
Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25–65 yr) had a glucose tolerance test...
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| Published in | The journal of clinical endocrinology and metabolism Vol. 90; no. 5; pp. 2636 - 2641 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Bethesda, MD
Oxford University Press
01.05.2005
Copyright by The Endocrine Society Endocrine Society |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-972X 1945-7197 |
| DOI | 10.1210/jc.2004-2190 |
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| Abstract | Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25–65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms−1 per minute−1), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 ± 30 to 419 ± 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect. |
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| AbstractList | Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25–65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms−1 per minute−1), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 ± 30 to 419 ± 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect. Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect. Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms per minute), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 ± 30 to 419 ± 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect. Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect.Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect. |
| Author | Pitteloud, Nelly Valassi, Elena Dwyer, Andrew A. Elahi, Dariush Hayes, Frances J. Hardin, Megan Yialamas, Maria |
| AuthorAffiliation | Reproductive Endocrine Unit (N.P., M.H., A.A.D., E.V., M.Y., F.J.H.), Department of Medicine (D.E.), Massachusetts General Hospital, Boston, Massachusetts 02114; and Department of Surgery, University of Massachusetts Medical Center (D.E.), Worcester, Massachusetts 01655 |
| AuthorAffiliation_xml | – name: Reproductive Endocrine Unit (N.P., M.H., A.A.D., E.V., M.Y., F.J.H.), Department of Medicine (D.E.), Massachusetts General Hospital, Boston, Massachusetts 02114; and Department of Surgery, University of Massachusetts Medical Center (D.E.), Worcester, Massachusetts 01655 |
| Author_xml | – sequence: 1 givenname: Nelly surname: Pitteloud fullname: Pitteloud, Nelly organization: 1Reproductive Endocrine Unit (N.P., M.H., A.A.D., E.V., M.Y., F.J.H.), Boston, Massachusetts 02114 – sequence: 2 givenname: Megan surname: Hardin fullname: Hardin, Megan organization: 1Reproductive Endocrine Unit (N.P., M.H., A.A.D., E.V., M.Y., F.J.H.), Boston, Massachusetts 02114 – sequence: 3 givenname: Andrew A. surname: Dwyer fullname: Dwyer, Andrew A. organization: 1Reproductive Endocrine Unit (N.P., M.H., A.A.D., E.V., M.Y., F.J.H.), Boston, Massachusetts 02114 – sequence: 4 givenname: Elena surname: Valassi fullname: Valassi, Elena organization: 1Reproductive Endocrine Unit (N.P., M.H., A.A.D., E.V., M.Y., F.J.H.), Boston, Massachusetts 02114 – sequence: 5 givenname: Maria surname: Yialamas fullname: Yialamas, Maria organization: 1Reproductive Endocrine Unit (N.P., M.H., A.A.D., E.V., M.Y., F.J.H.), Boston, Massachusetts 02114 – sequence: 6 givenname: Dariush surname: Elahi fullname: Elahi, Dariush organization: 2Department of Medicine (D.E.), Massachusetts General Hospital, Boston, Massachusetts 02114 – sequence: 7 givenname: Frances J. surname: Hayes fullname: Hayes, Frances J. email: fhayes@partners.org organization: 1Reproductive Endocrine Unit (N.P., M.H., A.A.D., E.V., M.Y., F.J.H.), Boston, Massachusetts 02114 |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16779690$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/15713702$$D View this record in MEDLINE/PubMed |
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| Keywords | Human Pancreatic hormone Androgen Secretion Male Testicle Male genital system Insulin Leydig cell Target tissue resistance Testosterone Adult Insulin resistance Testicular hormone Sex steroid hormone Endocrinology |
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| Snippet | Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the... |
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| SubjectTerms | Adult Aged Biological and medical sciences Chorionic gonadotropin Diabetes mellitus Endocrinopathies Fundamental and applied biological sciences. Psychology Glucose Glucose tolerance Gonadotropin-releasing hormone Gonadotropins Humans Hypogonadism Hypothalamic-pituitary-gonadal axis Hypothalamus Insulin Resistance Leptin - blood Leydig Cells - secretion Luteinizing Hormone - blood Male Medical sciences Middle Aged Pituitary Pituitary (anterior) Pituitary-gonadal axis Secretion Sensitivity analysis Sex Hormone-Binding Globulin - analysis Testosterone Testosterone - secretion Vertebrates: endocrinology Waist-Hip Ratio |
| Title | Increasing Insulin Resistance Is Associated with a Decrease in Leydig Cell Testosterone Secretion in Men |
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