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Reduced basal ATP synthetic flux of skeletal muscle in patients with previous acromegaly.

Szendroedi J, Zwettler E, Schmid AI, Chmelik M, Pacini G, Kacerovsky G, Smekal G, Nowotny P, Wagner O, Schnack C, Schernthaner G, Klaushofer K, Roden M - PLoS ONE (2008)

Bottom Line: AM had approximately 3 fold higher HCL (p<0.05) while IMCLt and IMCLs did not differ between the groups.Humans with a history of acromegaly exhibit reduced insulin secretion, muscular ATP synthesis and oxidative capacity but elevated liver fat content.This suggests that alterations in ss-cell function and myocellular ATP production may persist despite normalization of GH secretion after successful treatment of acromegaly.

View Article: PubMed Central - PubMed

Affiliation: 1st Med. Department and Karl-Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital, Vienna, Austria.

ABSTRACT

Background: Impaired mitochondrial function and ectopic lipid deposition in skeletal muscle and liver have been linked to decreased insulin sensitivity. As growth hormone (GH) excess can reduce insulin sensitivity, we examined the impact of previous acromegaly (AM) on glucose metabolism, lipid storage and muscular ATP turnover.

Participants and methods: Seven AM (4f/3 m, age: 46+/-4 years, BMI: 28+/-1 kg/m(2)) and healthy volunteers (CON: 3f/4 m, 43+/-4 years, 26+/-2 kg/m(2)) matched for age and body mass underwent oral glucose testing for assessment of insulin sensitivity (OGIS) and ss-cell function (adaptation index, ADAP). Whole body oxidative capacity was measured with indirect calorimetry and spiroergometry. Unidirectional ATP synthetic flux (fATP) was assessed from (31)P magnetic resonance spectroscopy (MRS) of calf muscle. Lipid contents of tibialis anterior (IMCLt) and soleus muscles (IMCLs) and liver (HCL) were measured with (1)H MRS.

Results: Despite comparable GH, insulin-like growth factor-1 (IGF-I) and insulin sensitivity, AM had approximately 85% lower ADAP (p<0.01) and approximately 21% reduced VO(2)max (p<0.05). fATP was similarly approximately 25% lower in AM (p<0.05) and related positively to ADAP (r = 0.744, p<0.01), but negatively to BMI (r = -0.582, p<0.05). AM had approximately 3 fold higher HCL (p<0.05) while IMCLt and IMCLs did not differ between the groups.

Conclusions: Humans with a history of acromegaly exhibit reduced insulin secretion, muscular ATP synthesis and oxidative capacity but elevated liver fat content. This suggests that alterations in ss-cell function and myocellular ATP production may persist despite normalization of GH secretion after successful treatment of acromegaly.

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Whole-body insulin sensitivity, maximal oxygen consumption and muscle mitochondrial ATP production (means±SEM): (A) OGIS (B) VO2max (p<0.05) and (C) flux through ATP synthesis (fATP) (p<0.05) in 7 subjects with previous acromegaly (AM, full bars) and 7 age- and body mass index-matched controls (CON, empty bars).
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pone-0003958-g001: Whole-body insulin sensitivity, maximal oxygen consumption and muscle mitochondrial ATP production (means±SEM): (A) OGIS (B) VO2max (p<0.05) and (C) flux through ATP synthesis (fATP) (p<0.05) in 7 subjects with previous acromegaly (AM, full bars) and 7 age- and body mass index-matched controls (CON, empty bars).

Mentions: Anthropometric and laboratory data are summarized in Table 1. In AM, fasting plasma concentrations of IGF-I and GH did not differ from CON and were within the normal range indicating successful treatment of the patients with previous acromegaly. Fasting plasma glucose was ∼17% higher in AM (p<0.05) and four patients had impaired fasting glucose (defined as fasting plasma glucose levels of 5.6 to 6.9 mmol/l), whereas plasma insulin and C-peptide were not different. All but one participant had normal glucose tolerance (as defined by the 2-h plasma glucose concentration less than 7.8 mmol/l the during OGTT) during active acromegaly and at follow-up visits following successful treatment. Fasting plasma insulin and C-peptide related positively to IGF-I levels (r = 0.552 and r = 0.646, p<0.05). Insulin secretion indices (ADAP, ISEC) were ∼85% lower in AM than in CON (p<0.05). Insulin sensitivity (OGIS) was comparable between groups (Figure 1) and correlated negatively with fasting plasma FFA (r = −0.744, p<0.05). FFA further related positively to GH levels (r = 0.782, p<0.01).


Reduced basal ATP synthetic flux of skeletal muscle in patients with previous acromegaly.

Szendroedi J, Zwettler E, Schmid AI, Chmelik M, Pacini G, Kacerovsky G, Smekal G, Nowotny P, Wagner O, Schnack C, Schernthaner G, Klaushofer K, Roden M - PLoS ONE (2008)

Whole-body insulin sensitivity, maximal oxygen consumption and muscle mitochondrial ATP production (means±SEM): (A) OGIS (B) VO2max (p<0.05) and (C) flux through ATP synthesis (fATP) (p<0.05) in 7 subjects with previous acromegaly (AM, full bars) and 7 age- and body mass index-matched controls (CON, empty bars).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2599885&req=5

pone-0003958-g001: Whole-body insulin sensitivity, maximal oxygen consumption and muscle mitochondrial ATP production (means±SEM): (A) OGIS (B) VO2max (p<0.05) and (C) flux through ATP synthesis (fATP) (p<0.05) in 7 subjects with previous acromegaly (AM, full bars) and 7 age- and body mass index-matched controls (CON, empty bars).
Mentions: Anthropometric and laboratory data are summarized in Table 1. In AM, fasting plasma concentrations of IGF-I and GH did not differ from CON and were within the normal range indicating successful treatment of the patients with previous acromegaly. Fasting plasma glucose was ∼17% higher in AM (p<0.05) and four patients had impaired fasting glucose (defined as fasting plasma glucose levels of 5.6 to 6.9 mmol/l), whereas plasma insulin and C-peptide were not different. All but one participant had normal glucose tolerance (as defined by the 2-h plasma glucose concentration less than 7.8 mmol/l the during OGTT) during active acromegaly and at follow-up visits following successful treatment. Fasting plasma insulin and C-peptide related positively to IGF-I levels (r = 0.552 and r = 0.646, p<0.05). Insulin secretion indices (ADAP, ISEC) were ∼85% lower in AM than in CON (p<0.05). Insulin sensitivity (OGIS) was comparable between groups (Figure 1) and correlated negatively with fasting plasma FFA (r = −0.744, p<0.05). FFA further related positively to GH levels (r = 0.782, p<0.01).

Bottom Line: AM had approximately 3 fold higher HCL (p<0.05) while IMCLt and IMCLs did not differ between the groups.Humans with a history of acromegaly exhibit reduced insulin secretion, muscular ATP synthesis and oxidative capacity but elevated liver fat content.This suggests that alterations in ss-cell function and myocellular ATP production may persist despite normalization of GH secretion after successful treatment of acromegaly.

View Article: PubMed Central - PubMed

Affiliation: 1st Med. Department and Karl-Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital, Vienna, Austria.

ABSTRACT

Background: Impaired mitochondrial function and ectopic lipid deposition in skeletal muscle and liver have been linked to decreased insulin sensitivity. As growth hormone (GH) excess can reduce insulin sensitivity, we examined the impact of previous acromegaly (AM) on glucose metabolism, lipid storage and muscular ATP turnover.

Participants and methods: Seven AM (4f/3 m, age: 46+/-4 years, BMI: 28+/-1 kg/m(2)) and healthy volunteers (CON: 3f/4 m, 43+/-4 years, 26+/-2 kg/m(2)) matched for age and body mass underwent oral glucose testing for assessment of insulin sensitivity (OGIS) and ss-cell function (adaptation index, ADAP). Whole body oxidative capacity was measured with indirect calorimetry and spiroergometry. Unidirectional ATP synthetic flux (fATP) was assessed from (31)P magnetic resonance spectroscopy (MRS) of calf muscle. Lipid contents of tibialis anterior (IMCLt) and soleus muscles (IMCLs) and liver (HCL) were measured with (1)H MRS.

Results: Despite comparable GH, insulin-like growth factor-1 (IGF-I) and insulin sensitivity, AM had approximately 85% lower ADAP (p<0.01) and approximately 21% reduced VO(2)max (p<0.05). fATP was similarly approximately 25% lower in AM (p<0.05) and related positively to ADAP (r = 0.744, p<0.01), but negatively to BMI (r = -0.582, p<0.05). AM had approximately 3 fold higher HCL (p<0.05) while IMCLt and IMCLs did not differ between the groups.

Conclusions: Humans with a history of acromegaly exhibit reduced insulin secretion, muscular ATP synthesis and oxidative capacity but elevated liver fat content. This suggests that alterations in ss-cell function and myocellular ATP production may persist despite normalization of GH secretion after successful treatment of acromegaly.

Show MeSH
Related in: MedlinePlus