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


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.
Szendroedi
Julia
J
1st Med. Department and Karl-Landsteiner Institute for Endocrinology and Metabolism, Hanusch Hospital, Vienna, Austria.
Zwettler
Elisabeth
E
Schmid
Albrecht Ingo
AI
Chmelik
Marek
M
Pacini
Giovanni
G
Kacerovsky
Gertrud
G
Smekal
Gerhard
G
Nowotny
Peter
P
Wagner
Oswald
O
Schnack
Christoph
C
Schernthaner
Guntram
G
Klaushofer
Klaus
K
Roden
Michael
M
D000172:Acromegaly / Q000378:metabolism* / Q000503:physiopathology / Q000534:rehabilitation*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D001481:Basal Metabolism / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D016022:Case-Control Studies; D015536:Down-Regulation; D015444:Exercise / Q000502:physiology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology
D000255:Adenosine Triphosphate