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- Title
Muscle Mitochondrial Dysfunction Is Associated with Reduced Beta Cell Function in Patients with Previous Acromegaly.
- Authors
Szendroedi, Julia; Zwettler, Elisabeth; Schmid, Albrecht I.; Chmelik, Marek; Pacini, Giovanni; Kacerovsky, Gertrud; Schnack, Christoph; Schernthaner, Guntram; Wagner, Oswald; Klaushofer, Klaus; Roden, Michael
- Abstract
Mitochondrial gene mutations lead to mitochondrial diabetes with defects of insulin secretion and sensitivity. Mitochondrial dysfunction is also involved in common insulin resistance, but secondary metabolic events may be confounding the metabolic picture in overt type 2 diabetes. Acromegaly is associated with alterations of energy expenditure and insulin action and might serve as model to investigate the role of mitochondrial function. Thus, we examined glucose metabolism, intracellular fat deposition and mitochondrial function in patients with a history of acromegaly (AM). Six AM (4f/2m, age: 49±4 years, body mass index, BMI: 27±1 kg/m²) with an at least 7-years history of successful treatment and age-/BMI-matched healthy volunteers (CON: 3 f/3m, 43±5 years, 26±2 kg/m²) were studied. Insulin sensitivity (OGIS), first-phase and adaptive insulin secretion were assessed from the frequently sampled OGTT (insulinogenic index, ISEC, adaptation index ADAP). Fasting mitochondrial function was assessed from ATP synthetic flux (fATP) using [sup 31]P magnetic resonance spectroscopy (MRS) of calf muscle. Intracellular lipid contents of tibialis anterior (IMCLt) and soleus muscles (IMCLs) as well as liver (HCL) were measured with [sup 1]H MRS. IGF-1 did not differ between groups (AM: 1774-36; CON: 145±21 ng/ml). Fasting plasma glucose was ∼16% higher in AM than in CON (99±3 vs. 85±2 mg/dl, p<0.05). OGIS was comparable (AM: 395±30, CON: 415±6 ml.min[sup -1].m[sup -2]), whereas ISEC was ∼87% (AM: 0.9±0.4, CON: 6.7±1.7 pmol/mmol, p<0.05) and ADAP was ∼84% lower in AM (0.44±0.19, CON: 2.77∼0.7 min[sup -2]/mmol.l[sup -1] p<0.05), fATP was ∼22% lower in AM (10.1±0.6 vs. 12.9±1.0 mmol.l[sup -1]min[sup -1], p<0.05) and related positively to ISEC (r=.687, p<0.01) and ADAP (r=0.744, p<0.005). IMCLt, IMCLs and HCL were not different between groups. IMCLs related negatively to insulin sensitivity (r=-0.745, p=0.005). Patients with a history of acromegaly exhibit reduced β cell and muscle mitochondrial function despite normal insulin sensitivity. Previous long-term exposure to high growth hormone and IGF concentrations and/or chronic increases in plasma glucose concentrations could lead to similar abnormalities in both tissues.
- Subjects
ACROMEGALY; MITOCHONDRIAL pathology; PANCREATIC beta cells; INSULIN resistance; BLOOD sugar; INSULIN-like growth factor-binding proteins
- Publication
Diabetes, 2007, Vol 56, pA376
- ISSN
0012-1797
- Publication type
Article